American March,

Heart

1979, Volume 97, Number

Journal

3

Editorial Mitral mitral

valve prolapse, the specific billowing leaflet syndrome, or an insignificant

non-ejection

systolic

click

John B. Barlow, M.D., F.R.C.P. Wendy A. Pocock, M.B., F.R.C.P. Johannesburg,

S. Africa

tor and the sine qua non for the diagnosis.” That may be true, but when or how do we diagnose MVP as an abnormal entity? Both in symptomatic and asymptomatic subjects, MVP has been detected cineangiocardiographically or echocardiographically in the absence of auscultatory features or other manifestations.8, “. Ii Conversely, and far more commonly in our experience, we have detected definite, albeit sometimes soft, non-ejection systolic clicks in subjects, again either symptomatic or asymptomatic and with or without electrocardiographic changes, in whom we have been unable to demonstrate echocardiographic or cineangiocardiographic confirmation of MVP. In our view, it is mandatory to identify the specific syndrome, which we have previously’ called the “billowing mitral leaflet syndrome” (BMLS) and to distinguish this primary”. i. I” or idiopathic”. II. Ii. 18 MVP from that secondary to pathological processes. Unlike previously,’ however, in this editorial the term BMLS will be confined to situations in which symptoms are associated with features of primary MVP. The BMLS occurs in both sexes and can probably manifest at virtually all ages. It is most common in young and middle-aged females and sometimes has a familial incidence. The BMLS is almost certainly due to a primary leaflet or chordal abnormality with, in some instances, and especially when the degree of MVP is severe, second-

In 1975 we endeavored’ to clarify aspects of mitral valve prolapse (MVP) and to discuss problems and unanswered questions relating to this common but somewhat ill-defined entity. Since that time there have been a plethora of papers relating to the subject, aptly called an “information explosion” by Devereux and colleagues.’ These have included studies providing data on clinical, echocardiographic and cineangiographic features, the prevalence, underlying pathology and associated conditions, the complications, prognosis and other aspects. In addition, attempts have been made’-‘3 to correlate the accumulated data and to place various manifestations of MVP in perspective. It is important now to assess which questions have been answered and what problems have not been solved. Although there remain many aspects which are not understood or require clarification, perhaps it is most important at this time to suggest how the individual patient or subject presenting with one or more features of so-called MVP should be classified, advised, and treated. Devereux and associates’ stated that “mitral leaflet prolapse remains the common denominaFrom the Cardiovascular Research Unit, Department of Medicine, University of the Witwatersrand and the Cardiac Clinic, Johannesburg Hospital, Johannesburg, South Africa. Received for publication Sept. 1, 1978. Reprint requests: Professor J. B. Barlow, Cardiac Unit, Johannesburg Hospital, Johannesburg, 2001, South Africa.

0002-8703/79/030277

+ 09$00,90/O

CD1979 The

C. V. Mosby

Co.

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ary myocardial distortion’. Ii. I9 or mild dysfunction.‘” Possibly the syndrome is currently being overdiagnosed but patients with symptoms such as palpitations, chest pain, syncope or breathlessness so frequently have the typical auscultatory and other features that its existence and importance must remain undisputed. The BMLS is most commonly encountered by us in patients referred because of symptoms in whom a nonejection systolic click, with or without a nonpansystolic (early or late) murmur of mild mitral regurgitation, is detected on auscultation.’ MVP may or may not be confirmed echocardiographitally or cineangiocardiographically and the electrocardiogram can be normal or abnormal. A problem relating to both diagnosis and management arises when similar auscultatory features are detected in asymptomatic subjects referred either for an assessment of the auscultatory signs or because of T wave changes on the electrocardiogram-in either instance usually detected at a routine or life insurance examination. Relevant to these asymptomatic subjects is the surprisingly high prevalence of auscultatory or echocardiographic features of MVP which has been found in recent surveys of “normal” population groups. These have ranged from 6.3 per cent” to nearly 18 per cent.‘Y We have encountered an analogous situation on routine examination of electrocardiograms of healthy young women who are prospective employees, as air hostesses, of South African Airways. A number of these girls have had ST segment and T wave changes, compatible with the BMLS, and have then been examined by one of us (J.B.B.). Auscultation may or may not reveal the presence of a non-ejection systolic click and, less frequently, an associated non-pansystolic murmur. It is, regrettably, not understood by us why a relatively large number of asymptomatic subjects have auscultatory, echocardiographic, and even electrocardiographic features of MVP identical to symptomatic patients referred for assessment and treatment and in whom we make a diagnosis of the BMLS. It appears to us, however, that it has now become essential for the symptomatic and asymptomatic groups to be differentiated. It has recently been stated by Motulsky,‘” and in our view probably correctly, that “for every patient with symptomatic mitral valve prolapse. . ., there are hundreds of asymptomatic persons.” We shall later discuss some differences in our suggested management of

278

the BMLS patients from that of subjects with identical features of primary MVP except that they are asymptomatic. In general, like Cobbs,‘!’ we have found that subjects with isolated systolic clicks are often asymptomatic and that electrocardiographic abnormalities are less common, whereas those with clicks and constant late systolic murmurs are more likely to have symptoms, ST segment and T wave abnormalities and arrhythmias. Symptoms and electrocardiographic changes may be related to the extent of the mitral billow, and hence the tug on the papillary muscle, but patients with marked prolapse are not necessarily symptomatic and, conversely, mild MVP may be associated with numerous symptoms. A late systolic murmur which starts shortly after the first heart sound or which becomes pansystolic on standing or after amyl nitrite inhalation is indicative of more severe MVP. Both procedures reduce the size of the left ventricular cavity so that the mitral leaflets become relatively more redundant with consequent increase in the degree of prolapse. The large number of patients with the BMLS who suffer from anxiety is noteworthy and is not always understood. In some, anxiety supervenes after an incorrect diagnosis of occlusive coronary artery disease has been made.‘:’ In others, anxiety in a genuinely symptomatic patient with the BMLS may be caused or aggravated by the insistence of medical attendants that there is no organic heart disease present. It is not “reassuring” to patients with disturbing symptoms, such as chest pain or palpitations, to be told that they are “neurotic.“’ We postulated,’ as later did Wooley,” that many cases of so-called DaCosta’s syndrome or neurocirculatory asthenia are examples of the BMLS. It is important, but sometimes difficult, to distinguish the BMLS and so-called primary or idiopathic MVP, from secondary MVP. The numerous conditions’. “. L’i-ix which cause or are associated with MVP are reflected in Table I and we have attempted to differentiate the conditions which are probably causally related as opposed to those which may be chance associations. Inevitably, there will often be an overlap and some entities, most importantly myocardial ischemia, rheumatic valvulitis, cardiomyopathy, and viral myocarditis may sometimes cause MVP and sometimes be a chance association with primary

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1979,

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MVP,

Table

I. Documented

conditions

Definite

or probable

Primary MVP (BMLS) Marfan syndrome Floppy valve syndrome Rheumatic endocarditis Occlusive coronary artery disease Congestive cardiomyopathy Idiopathic hypertrophic subaortic Myocarditis Mitral valve surgery Trauma Left atria1 myxoma Polyarteritis nodosa Left ventricular aneurysm Ehlers-Danlos syndrome”t Relapsing polychondritis”,t Lupus erythematosuSt Muscular dystrophyz7t Wolff-Parkinson-White syndrome”-“‘t *Abbreviations not in text: TReferences are given only

Heart

cause

Probable

I

click

stenosis

association

Congenital heart disease (atria1 septal defect, ventricular septal defect, patent ductus arteriosus, complete absence left pericardium,“? membranous subaortic stenosis,“? Ebstein’s anomaly,” “t corrected transposition of great vessels i ‘t) Athlete’s heart Turner’s syndrome”,+ Noonan’s syndrome”t Congenital prolonged Q-T syndrome”t

NESC = non-ejection systolic click; MISM = mitral incompetent for conditions which were not mentioned in Barlow and Pocock.’

Journal

or non-ejection

causing or associated with MVP or NESC/MISM*

MVP. It may be impossible to detect at a single examination which underlying pathological factor is relevant. There must necessarily be a few patients in whom a diagnosis of asymptomatic primary MVP or of the BMLS is made but in whom the auscultatory and other features are due to the floppy valve syndrome’3”. A1’(with or without skeletal manifestations of the Marfan syndrome in relatives), rheumatic valvular disease, or papillary muscle dysfunction. The papillary muscle dysfunction in turn may have resulted from past acute viral myocarditis or reflect an early manifestation of occlusive coronary artery disease or cardiomyopathy. The BMLS is probably a cause of conduction defects’, l’. 1? as well as supraventricular and ventricular arrhythmias,‘, “. 6, B.lri. “‘-li but the pathogenesis of these is not understood and again a chance association must sometimes apply. The association of MVP with the Wolff-ParkinsonWhite syndrome has been emphasized.‘. Zx-,lo.J1 Is this conduction defect caused by primary MVP, is it a chance association, or does the abnormal activation of ventricular contraction result in MVP? The latter explanation is, in our view, most frequently applicable. The differentiation of the BMLS from occlusive coronary artery disease (OCAD) and the relationship between OCAD and MVP is of great importance. The differentiation of the BMLS

American

BMLS,

systolic

murmur.

with an abnormal electrocardiogram from MVP due to OCAD is clearly much easier in a 20year-old woman than it is in a 45-year-old man. Even in the latter instance, however, it is our experience that an accurate history, physical examination, and the post-effort electrocardiogram usually suffice to distinguish the two conditions. The chest pain of the BMLS is often unlike that of angina pectoris in that it is fleeting, left-sided, and has no relation to exercise or emotion. In some instances, however, the description of the pain is identical to that of angina pectoris in that it is central, constricting, and may radiate to the left arm. Despite this similarity, we have observed that the duration as well as the factors affecting the onset and offset of the pain may be unusual for OCAD. The problem of MVP, the BMLS, and OCAD can be considered under the following five subdivisions: 1. MVP

resulting

from

OCAD

Several series’. “i-ix of patients with late systolic murmurs or non-ejection clicks have contained a few subjects in whom OCAD has been assumed to be the cause of the auscultatory signs on the basis of papillary muscle dysfunction.“‘-j’ These have usually been middle-aged or older men with angina pectoris or previous myocardial infarction, in some of whom significant coronary artery disease has been confirmed arteriographically. A

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causal relationship is difficult to establish unless the click or murmur has been observed to develop5’ or, more conclusively, if the patient had been studied by angiography or echocardiography before the ischemic event.“’ More recently, the prevalence of MVP in patients with OCAD has been investigated”. 5.1.j-l and some degree of MVP, usually involving the posterior leaflet, has been found in from 19.2 per cent14 to 60 per cent”’ of cases. Although there have usually been fibrosis of papillary muscle and underlying myocardium at necropsy, occasionally there has been no detectable abnormality14 and a functional disturbance has been postulated. The valve leaflets and chordae have been normal. Echocardiography has been positive in only a small proportion of patients with MVP demonstrated angiographically”’ and in very few have there been auscultatory signs.g”. ii This apparent dissociation of angiographic from clinical and echocardiographic features in patients with MVP secondary to OCAD is difficult to explain and Jeresaty’” has attributed it to an absence of leaflet or chordal abnormality. Although exact figures are not available, a soft non-ejection click has been detected”’ in many patients admitted to our coronary care unit with an acute ischemic event. We think it possible that these sounds could easily be overlooked. It is our impression, but we have no hard data on this, that patients who develop MVP after acute myocardial infarction more often complain of symptoms like those of the BMLS, such as atypical left chest pain and palpitations, than do patients with no definite MVP after acute infarction. 2. Coincidental OCAD

primary

MVP

(or the BMLS)

and

Both OCAD and primary MVP are common and there has to be a number of patients with both conditions.‘“. 5x The electrocardiogram, at rest or after effort, is usually abnormal and changes more suggestive of OCAD or of the BMLS may predominate. Where selective coronary arteriography confirms the OCAD and left ventriculography shows relatively mild MVP, it is difficult or impossible to be certain whether the MVP is primary or due to the OCAD. Where the degree of MVP is marked, we favor the conclusion that the two conditions are occurring coincidentally.

3. Primary cardiogram

MVP (or the BMLS) atypical for OCAD

with

an electro-

This group includes non-specific T wave changes, the ST segment, and T wave changes described in the BMLS and the abnormal electrocardiograms recorded in some athletes.’ The T wave changes normalize immediately after effort in the majority of patients. Where the electrocardiogram becomes more abnormal in the postexercise recordings the changes are atypical for myocardial ischemia.’ Selective coronary arteriography is normal.’ 4. Primary cardiogram

MVP (or the BMLS) with an electroindistinguishable from OCAD

So-called “false-positive” post-effort electrocardiograms are reputedly more common in females.“” In either sex, however, a middle-aged patient with auscultatory and other features of MVP, chest pain suggestive of angina pectoris, and more than 1 mm. horizontal or down-sloping ST segment depression occurring after effort and lasting for several minutes, may indeed cause difficulty in diagnosis.‘. I“. iii1Engel and co-workers”’ reported such abnormal repolarization responses to treadmill exercise testing in seven of 23 male aircrew members with MVP and normal coronary arteries. Six of the seven were asymptomatic. Malcolm and Ahuja’” studied 38 patients with MVP by electrocardiographically monitored submaximal exercise stress testing and concluded that the response differed from that considered typical of ischemia, mainly in that the ST segment abnormalities developed immediately after effort and were short-lived or, alternatively, occurred only at 8 minutes or even later. None the less, we have encountered a few patients in whom we had no means of distinguishing with certainty the BMLS from OCAD other than by selective coronary arteriography (Fig. 1). It is in this group that thallium-201 myocardial scintigraphy may prove contributory in excluding regional myocardial ischemia and thus make t,he presence of significant OCAD unlikely.“. ” This technique has been said’> to be more accurate than exercise electrocardiography in identifying large vessel ischemia. However, there have been recent reports”4, ‘ii of the patterns of regional myocardial ischemia in patients with MVP and normal coronary arteries and greater experience is needed in interpretation of this relatively new investigation in cases of MVP. The possibility of

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1979, Vol. 97, No. %

MVP,

myocardial &hernia is not excluded by a negative exercise perfusion scintigram nor by anatomically normal coronary arteries but the patient should then be considered under subdivision 5. 5. Primary MVP (or ischemia or infarction arteriography

the and

BMLS), normal

myocardial coronary

The entity of myocardial ischemia or infarction with anatomically normal coronary arteries is now generally accepted.“” Several investigators”‘. Dxfavor the conclusion that coronary artery spasm causes the ischemia or infarction, but the reason for such spasm is unknown. Chesler and co-worker+’ reported four patients with MVP, acute myocardial infarction, and normal coronary arteriograms and postulated that there may be an association between the BMLS and coronary artery spasm. Cerebral ischemic events, attributed to bland emboli, have been reported% 70-i” in cases of MVP and it is possible that small coronary artery emboli provoked spasm in Chesler’s cases. If this is true, a therapeutic trial of dipyridamole (Persantin) and salicylates may be indicated in similar cases. The association between MVP and coronary spasm with anatomically normal vessels was observed in one patient by Awdeh and Gholston.‘,’ More recently, Buda and co-workers’J confirmed an association between coronary artery spasm and MVP. Nine of their 10 patients with coronary artery spasm had MVP. The possible association between the BMLS and coronary artery spasm requires further observations and study. The mechanism of the chest pain, arrhythmias, electrocardiographic abnormalities, and conduction defects in the BMLS is unknown.’ Buda and associates74 postulate that coronary artery spasm may be an important factor, and Cobbs’” has suggested that local coronary spasm might contribute to papillary muscle &hernia. Cowley and colleagueS:‘9 reported a patient with severe, typical angina pectoris, isolated corrected transpostion of the great vessels, normal coronary arteries, and bilateral atrioventricular valve prolapse. The cause of the chest pain in their patient was not understood. Management

and

prognosis

The prognosis of a patient with MVP largely depends on whether there is an underlying cause

American

Heart

Journal

BMLS,

or non-ejection

click

CONTROL AVF

POST

EXERCISE

immed.

2 mins

5 mins

10 mins

15 mins

Fig. 1. Pre- and post-exercise electrocardiograms of a 3.5. year-old man with angina-like chest pain and a loud nonejection systolic click. We interpreted the ST and T wave changes, especially in Leads II, III and aV,. at 2 and 5 minutes, as compatible with occlusive coronary artery disease. Selective coronary arteriography was normal.

or associated condition. This is readily apparent when MVP occurs with OCAD or a cardiomyopathy. Conditions such as the Wolff-ParkinsonWhite syndrome, congenital heart disease, and the congenitally prolonged QT syndrome are as important, or more so, than the MVP itself. It is therefore relevant to know of accompanying or causal pathological entities when assessing myocardial function, arrhythmias, conduction defects, or the possibility of sudden death in patients who have MVP. It would not be meaningful, for example, to attribute the cause of sudden death in a patient with triple vessel OCAD to coincidentally associated primary MVP or to MVP secondary to papillary muscle dysfunction. The series of Raizada and asso-

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ciatesT4 indicated, in fact, that MVP is extremely common with triple vessel OCAD. Symptomatic idiopathic or primary MVP-the BMLS. Reassurance as to the generally excellent

prognosis for life is essential in the management of these symptomatic and often anxious patients.‘” Symptoms such as palpitations, lightheadedness, dizziness, or syncope suggest the presence of arrhythmias or conduction defects, but exercise electrocardiography or ambulatory monitoring may be necessary for confirmation. Arrhythmias may occasionally occur without such symptoms’ ‘.l. ;‘, and, conversely, dizziness and palpitations have been prominent complaints at times when electrocardiographic monitoring’.’ or clinical examination4 j, 7Yprovided no objective explanation. When multifocal premature ventricular contractions, the R on T phenomenon, or ventricular tachycardia are detected, treatment with a beta-adrenergic blocking agent is recommended. Other potentially useful therapeutic agents include perhexiline maleate, diphenylhydantoin, disopyramide, and mexilitine. In our experience, a good response can be anticipated. There is evidence”. :‘. Z’ that the potentially serious arrhythmias are more common if the resting electrocardiogram shows ST segment and T wave changes. Nevertheless, the prognosis, even in this possibly higher risk group, appears to be good and sudden death is extremely rare. Chest pain, which may be a disabling symptom, usually also responds well to reassurance and a beta blocker, but an occasional patient is encountered who is refractory to both. Asymptomatic primary MVP. The management of the asymptomatic subject with an isolated non-ejection systolic click, whether loud, soft, or intermittent, and in some instances with an associated transient, non-pansystolic regurgitant murmur, is more controversial. Whether or not echocardiography or cineangiocardiography confirms or demonstrates mild MVP does not contribute to solving the problem of how to assess or treat these asymptomatic subjects, whom recent evidence”, ‘I’ suggests comprise a large percentage of the apparently healthy population and may represent a “normal variant.” Depending on the context of the situation in which the features of MVP were detected, the person should, in our view, either be reassured of the probable insignificance of the observation or else not be informed of it at all. An effort electrocar-

282

diogram is mandatory only if the individual is employed in an import,ant public service capacity, such as an airline pilot, or as part of the assessment for a life insurance policy. Although asymptomatic subjects may indeed develop arrhythmias after effort,‘, x the prognostic significance of this observation remains to be established. It is often customary to perform a stress electrocardiogram on asymptomatic persons with auscultatory features of MVP detect,ed at a routine examination, particularly if the resting electrocardiogram is abnormal. However, we have not practiced that policy on schoolchildren or air hostesses detected during surveys. Any patient, including a young woman, who consults a medical practitioner for a “check-up” will, in our experience, accept a stress electrocardiogram as part of the examination and that is our usual policy, especially when the resting electrocardiogram is abnormal. An air hostess, on the other hand, singled out from her peers for a stress test, would require an explanation, become anxious, and may even develop a cardiac neurosis. Should, in fact, the post-effort electrocardiogram have revealed ventricular ectopy, is there good evidence and thus sound reason to believe that the girl should be informed, then reassurance attempted and an antiarrhythmic agent prescribed? We contend not! Progression of mitral regurgitation. Subjects with a constant late systolic murmur generally have a less favorable prognosis than do those with an isolated non-ejection click. Echocardiography in this group usually confirms MVP. Although progression of the mitral regurgitation may not occur”. *’ or is slight and gradual over many years in some,“‘-“.’ it is difficult to identify the few subjects, usually men, in whom severe mitral regurgitation will supervene.*‘. ‘-l Many of the cases which progress to more severe mitral regurgitation may belong to the much rarer category of floppy valve syndrome. As has already been intimated, we know of no way of recognizing these in the early stage of MVP unless there are skeletal manifestations of the Marfan syndrome in the patient or in relatives. Although we favor that the term BMLS be confined to symptomatic patients with features of primary MVP and that asymptomatic subjects with a non-ejection click, even if accompanied by a transient non-pansystolic murmur, be regarded as “normal variants” who seldom require specific treatment or future

March,

1979,

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97, NO.

3

MVP,

observation, the asymptomatic individual with established, albeit mild, mitral regurgitation due to primary MVP has to become a “patient.” Periodic, though infrequent, clinical assessment for possible progression of the valve anomaly and advice regarding prophylaxis against infective endocarditis are indicated. Prophylaxis of infective endocarditis. Infective endocarditis may supervene in MVP and we are well aware%’ that occasional cases have been encountered in patients with an isolated nonejection systolic click. It is now recognized, however, that non-ejection clicks with or without transient mitral systolic murmurs are extremely common. The number of reported cases of infective endocarditis in MVP is still relatively small and in the majority established mitral regurgitation had previously been detected.“‘, ‘I’ Our current policy is to recommend prophylactic antibiotics at times of risk only to those patients who have established mitral regurgitation as reflected by a constant early, late, or pansystolic apical murmur. Prophylaxis in the large number of subject,s, whether symptomatic or not, whose only auscultatory feature is a non-ejection systolic click is impracticable.” Concluding

American

Heart

Journal

or non-ejection

click

Some of the symptoms of the BMLS result from observed potentially fatal arrhythmias and conduction defects. Notwithstanding, we still conclude from the published data and our own experience that the prognosis for life is excellent. Although we have a number of patients with the BMLS in whose families instances of unexplained sudden death at a young age had occurred,’ and despite our concern expressed over a decade agohi regarding the possibility of fatal arrhythmias supervening during exercise or emotion, we have not yet encountered an indisputable case of sudden death due to the BMLS. REFERENCES 1.

2.

3. 4.

5.

6.

remarks

There remain difficulties in assessing whether reputedly abnormal MVP, suspected because of auscultatory, echocardiographic, electrocardiographic or cineangiocardiographic features, is significant or a “normal variant” in the individual subject. In our view, the management of so-called primary MVP differs importantly, depending on whether or not the person is symptomatic. We have reserved the term BMLS for the symptomatic patient with features of primary MVP. Indisputable MVP may be secondary to, or coincidentally associated with, many pathological conditions which are of far greater relevance in determining the prognosis than is the MVP itself. The specific BMLS, a primary leaflet and chordal anomaly, is an important and common clinical entity in which the degree of MVP may be relatively mild despite disabling symptoms. Asymptomatic primary MVP and the BMLS in turn, have to be distinguished, but this is sometimes difficult, from the more rapidly progressive floppy valve syndrome or from the secondary causes of MVP such as OCAD, viral myocarditis, rheumatic endocarditis, and cardiomyopathy.

BMLS,

7. 8.

9.

10. 11.

12.

13.

14.

15.

16.

Barlow, J. B., and Pocock, W. A.: The problem of nonejection systolic clicks and associated mitral systolic murmurs: emphasis on the billowing mitral leaflet syndrome, AM. HEART J. 90:635, 1975. Devereux, R. B., Perloff, J. K., Reichek, N., and Josephson, M. E.: Mitral valve prolapse, Circulation 54:3, 1976. Abrams, J.: Mitral valve prolapse: a plea for unanimity (Editorial), AM. HEART J. 92:413, 1976. Aranda, J. M., Befeler, B., El-Sherif, N., Castellanos, A., and Lazarra, R.: Mitral valve prolapse. Recent concepts and observations, Am. J. Med. 60:997, 1976. Cheng, T. 0.: The chck-murmur syndrome. A medical pendulum and a unifying concept (Editorial), Chest 70:569, 1976. Criley, J. M., and Kissel, G. L.: Prolapse of the mitral valve-the click and late systolic murmur syndrome, in Progress in Cardiology, Goodwin, J., and Yu, P. F., eds., Philadelphia, 1976, Lea & Febiger, p. 23. Lesch, M.: Mitral valve prolapse: A clinical spectrum (Editorial), N. Engl. J. Med. 294:1117, 1976. Malcolm, A. D., Boughner, D. R., Kostuk, W. J., and Ahuja, S. P.: Clinical features and investigative findings in presence of mitral leaflet prolapse. Study of 85 consecutive patients, Br. Heart J. 38:244, 1976. Wigle, E. D., Rakowski, H., Ranganathan, N., and Silver, M. D.: Mitral valve prolapse, in Annual Review of Medicine, Creger, W. P. ed.. 27:165, 1976. Cantwell, J. D.: In Modern Cardiology, Boston, London, 1977, Butterworth & Co., Ltd., D. 119. Cobbs, B. W., and King, S. B.‘:‘Ventricular buckling: A factor in the abnormal ventriculogram and peculiar hemodynamics associated with mitral valve prolapse, AM. HEART J. 93:741. 1977. Gottlieb, R., and Chung, E. K.: Mitral valve prolapse-click syndrome, in Quick Reference to Cardiovascular Diseases. Chung, E. K.. ed., Philadelphia, Toronto, 1977, J. B. Lippincott Company, p. 87. Swartz, M. H., Teichholz, L. E.. and Donoso, E.: Mitral valve prolapse. A review of associated arrhythmias, Am. J. Med. 62:377, 1977. Verani, M. S., Caroll, R. J., and Falsetti, H. L.: Mitral valve prolapse in coronary artery disease, Am. d. Cardiol. 37:1, 1976. Smith, E. R., Fraser, D. B., Purdy, J. W., and Anderson, R. N.: Angiographic diagnosis of mitral valve prolapse: correlation with echocardiography, Am. J, Cardiol. 40~165, 1977. Crawford, M. H.: Mitral valve prolapse due to coronary artery disease, Am. J. Med. 62:447, 1977.

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35.

36.

37.

38.

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