The syndrome of papillary muscle dysfunction

Fundamentals of clinical cardiology

The syndrome

of papillary

muscle

dysfunction

G. E. Bwch, M.D. N. P. DePaspuale, M.D. J. H. Phillips, M.D. New Orleans, La.

N

ormal mitral valve function depends upon the anatomic and mechanical integrity of the atrioventricular ring, the valve leaflets, the chordae tendineae, and the papillary muscles, as well as upon proper integration of the time relations between contraction of the papillary muscle and contraction of the free left ventricular wall. Incompetence of the mitral valve due to congenital or acquired disease of the leaflets, the valve ring, the chordae tendineae, and related structures has long been recognized, whereas incompetence due to disease of the papillary muscles has received relatively little attention. Only recently have advances in the knowledge of papillary muscle function been sufficient to provide a more complete understanding of the over-all physiology and pathology of the mitral valve apparatus. As is frequently the case, through the study of disease the processes of normal function become more evident. This has been so in the areas under consideration, and the manifestations of dysfunction of the papillary muscles have been discussed in previous reports from this laboratory.l-3 In these reports, emphasis was placed upon the role of ischemia with or without infarction in the development of papillary From

muscle dysfunction. Although circulatory insufficiency is a major cause of the papillary muscle syndrome, there are many other pathophysiologic states which may result in papillary muscle dysfunction. The purpose of the present paper is to extend concepts previously presented as well as to provide a more comprehensive description of the papillary muscle syndrome. Although only dysfunction of the papillary muscles of the left ventricle is considered in this report, the same concepts may be extended to the papillary muscles of the right ventricle. Functional anatomy of the normal papillary muscle. Normal papillary muscle function has been described in detail elsewhere1-3 and therefore will be discussed only briefly here. There are two groups of papillary muscles in the left ventricle, the anterolateral group and the posteromedial group. The anterolateral papillary muscle arises from the anterolateral wall of the left ventricle and receives its blood supply primarily from marginal tributaries of the circumflex branch of the left coronary artery (Fig. l~!).~ In some hearts, the anterolateral papillary muscle receives a secondary blood supply from the anterior descending branch of the left coronary

the Department of Medicine of the Tulane University School of Medicine, the Charity Hospital and the Veterans Administration Hospital, New Orleans, La. Supported by grants from the United States Public Health Service, the Rudolph Matas Memorial Fund Prewitt Hess Laboratory, and the Rowe11 A. Billups Fund for Research in Heart Disease.

399

of Louisiana, for the Kate

400

lkch,

DePusquule,

Posferior Branch Coronary

trnd PhiLLi$s

Descendho of A

-Circumflex Brunch of Left Coronary Artery

”

Ahior Descending Branch of L eff Coronary Arfery 1;i.g. 1;1. Schematic

representatwn

of blood

supply

to the pap&u-y

artery (Fig. IA). The postevowzedial papillary muscle arises near the junction of the posterior wall of the left ventricle and the interventricular septum and is supplied with blood either by tributaries from the circumflex artery or by posterior descending branches from the right coronary artery (Fig, 1A). Details of the distribution of arterial vessels in the papillary muscles are shown in Figs. 113 and 1C. These small papillary arteries course longitudinally to the apex of the papillary muscle where they terminate in the arterioles, capillaries, venules, and small veins. At times these papillary arteries form arcuate anastomoses near the distal ends of the muscle. In the normal-sized heart, the long axis of the papillary muscle is oriented almost perpendicular to the atrioventricular ring. This orientation of the papillary muscles provides a mechanical advantage in that tension developed by the papillary muscles is applied almost perpendicular to the mitral valve leaflets. On the other hand, with ventricular dilatation the papillary muscles migrate laterally, so that tension developed by the papillary muscles is applied tangentially to the mitral leaflets. The greater the lateral displacement of the papillary muscles the greater the mechanical disadvantage. The function of the papillary muscles and chordae tendineae to restrain the movements of the mitral valve leaflets during ventricular systole is obvious. HOYever, the dynamic nature of this function is not always appreciated. Normal mitral

muscles

of the left

ventrick.

valve function depends upon the maintenance of the proper spatial relationships between the papillary muscles, the chordae tendineae, and the mitral valve leaflets throughout all phases of the cardiac cycle. During the isovolumetric phase of ventricular systole the rapid rise in intraventricular pressure causes the mitral valve leaflets to bulge towards the left atrium and to come into firm surface contact with each other, thus closing the atrioventricular orifice.j-* The movement of the mitral valve leaflets towards the atrium pulls the chordae tendineae taut (Fig. 2). In the interest of completeness, it may be stated that there is evidence that the mitral valve leaflets come into apposition to close the atrioventricular orifice just before the onset of ventricular systole.g Nevertheless, firm apposition of the leaflets probably does not occur until the onset of isovolumetric contraction, at which time the tw;o opposing forces of intraventricular pressure and papillary muscle tension assure that the portions of the mitral leaflets which are in apposition are tightly sealed. It should be understood that the chordae tendineae from each papillary muscle attach to the corresponding halves of both leaflets of the mitral valve. However, for purposes of simplification in illustrating the hemodynamic consequences of papillarymuscle dysfunction, each papillary muscle is shokvn as supplying a single leaflet in Figs. 1 through 6. The papillary muscles and chordae tendineae must support the force acting

Syndrome of papillary

Fig. 13. .-1 longitudinal section through the ventricles of a human hear-t. The arterial vessels have been injected and filled with a linely divided barium sulfate (Micropaqne) suspension in 10 per cent formalin. The whitish globules represent areas of extravasation of the barium. L VC, Left ventricular cavity; R VC, Right ventricular cavity; IVS, Interventricular septum; L;VFTT’, Left ventricular free wall; PM, Papillary muscle; MVL, Mitral valve leaflets; Ba, extravasated barium. The area enclosed by the rectangle represents that portion illustrated in Fig. IC.

the mitral valve, which is equal to the intraventricular pressure times the cross-sectional area of the atrioventricular orifice. In a previous report from this laboratory*O we have estimated, on the basis of certain theoretic considerations, that each papillary muscle of the left ventricle supports a total peak load of 19 tons during a 24 hour period for a heart rate of 70 beats per minute and an arterial blood pressure of 120/80 mm. Hg. During the ejection phase of ventricular systole, the apex of the left ventricle moves towards the atrioventricuIar orifice. Since the moment-to-moment length of the chordae tendineae is fixed, the papillary muscles must shorten during systole to maintain the proper distance between the base of the papillary muscles and the atrioventricular orifice in order to prevent eversion of a portion of the mitral leaflets upon

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401

into the left atrium. It is of interest that motion pictures of mitral valve moven~e~lt in the intact dog have demonstrated that the mitral valve leaflets move downward into the ventricle during ventricular systole rather than upward toward the atrium.rz Thus, contraction of the papillary muscles takes up the slack which would have been created in the chordae tendineae as a result of the shortening of the distance between the apex of the left ventricle and the atrioventricular orifice during the ejection phase of ventricular systole. Furthermore, the papillary muscles must develop sufficient tension to overcome intraventricular pressure. This latter point is important since the tension in the free wall of the left ventricle decreases or remains constant during the ejection phase of systoIe.r2 Therefore, while the muscle of the free wall of the left ventricle “loafs” during ventricular ejection, the papillary muscles must continue to develop more tension. pathologic

physiology

Significant alteration in the normal spatial relationships between the papillary muscles, chordae tendineae, and atrioventricular orifice at any time during ventricular systole may result in abnormal function of the mitral leaflets manifested by mitral valve incompetence. However, regardless of its etiology, the hemodynamic consequence of papillary inuscle dysfunction, i.e., mitral regurgitation, is always due to alteration in the normal spatial relationships between the various elements of the mitral valve apparatus. AbnormaIIy great tension or restraint on the mitral leaflets may pull the leaflets into the ventricle so that the firm apposition between leaflets necessary for cIosure of the atrioventricular orifice cannot occur. On the other hand, inadequate restraint on the mitral leaflets allows a portion of each leaflet to evert into the atrium, again preventing satisfactory closure of the atrioventricular orifice. As will be discussed later, a number of disease processes may result in too great or too little restraint on the mitral leaflets by the papillary muscles and chordae tendineae. The time course of the mitral insufficiency varies depending upon the nature of the papillary muscle

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Fig. 1C. Stereoscopic presentation of x-ray photographs of barium-filled vessels in the area of the !eft ventricle demarcated by the rectangle in Fig. fB. This figure may be viewed stereoscopically by placing a card between the two portions of the illustration and slowly moving the illustration away or toward one’s eyes until a threedimensional relationship is appreciated. With practice and adjustment of visual distance it is possible to obtain a three-dimensional image of this illustration with the unaided eyes. For those unable to do this, stereoscopic lenses may be employed. In this typical example, note the linear distribution of the papillary arteries coursing up through the papillary muscle and also the arcuate anastomosis of some of these vessels near the muscle tip. With such a vascular distribution as illustrated here, one can readily appreciate the vulnerability of the distal areas of the papillary muscle to ischemic injury.

ISOVOLUMETRIC

CONTRACTION

MAXIMAL EJECTION

Fig. 2. Normal papillary muscle function. For purposes of simplification in this illustration and in Figs. 3 through 6, a single chorda tendinea is depicted as supplying a single mitral leaflet; actually, chordae tendineae from both papillary muscles supply the corresponding half of each mitral leaflet (consult text). During isovolumetric contraction the mitral leaflets are in contact and bulge toward the atrium, pulling the chordae tendineae taut as intraventricular pressure increases. AS the musculature of the ventricle shortens during ejection, contraction of the posteromedial (5’2.) and anterolateral (A.P.) papillary muscles maintains a proper distance between the papillary muscles and valve leaflets, thus keeping the mitral valve closed during systole (From Burch, DePasquale, and Phillips: Arch. Int. Med. 112:112, 1963).

Volsw?w 75 Number 3

Syndrome of papillary

dysfunction, so that the characteristics of the associated murmur often provides a clue to the etiology of the papillary muscle dysfunction. Etiology

As already indicated, papillary muscle dysfunction may be due to a variety of disease processes (Table I); and regardless of whether the papillary muscle dysfunction is due to loss of anatomic or functional integrity, mitral incompetence is always due to alteration in the normal spatial relationships between the papillary muscles, chordae tendineae, and atrioventricular orifice. Diseases involving the chordae tendineae are included among the causes of papillary muscle dysfunction in Table I because the papillary muscles and chordae tendineae function as a unit. However, it should be clear that mitral valve disease with or without involvement of the chordae tendineae should not be considered as an example of the papillary muscle syndrome. Table I. Etiology function

of papillary

muscle dys-

Circulatory insufficiency (ischemia) Angina pectoris Infarction of papillary muscle Acute Chronic (fibrosis) Systemic circulatory disturbances (hypotension, erythrocytosis, anoxia, hematometakinesia, etc.) Left ventricular dilatation Generalized Localized (aneurysm) Nonischemic atrophy of papillary muscle Senile Associated with cachexia Defective development of papillary muscle apparatus Congenitally long or short papillary muscle or chordae tendineae Ectopic origin of papillary muscle Ectopic insertion of chordae tendineae Endocardial disease Endocarditis Endocardial fibroelastosis Endomyocardial fibrosis Heart muscle disease Inflammatory (myocarditis) Degenerative cardiomyopathy Infiltrative (metastatic carcinoma, amyloidosis) Neoplastic (primary tumor of myocardium) Disturbances in the time course of papillary muscle activation and contraction Rupture of papillary muscle or chordae tendineae

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403

Circulatory insuficiency. Probably the most common cause of papillary muscle dysfunction is circulatory insufficiency. The papillary muscles, being subendocardial structures, are supplied by terminal branches of the coronary arteries (Figs. lA, lB, and 1C).4 Moreover, they are the thickest portion of the endocardium. These factors combine to render the papillary muscles particularly vulnerable to ischemia. The papillary muscles may become ischemic not only as a result of narrowing of the coronary arteries but also as a result of disease states associated with diminished coronary artery perfusion. Because of the large amounts of tension which must be developed by the papillary muscles during ventricular systole, they are easily damaged by ischemia. Furthermore, in some hearts the major blood supply to both papillary muscles of the left ventricle is derived from the same artery (circumflex branch of left coronary artery), so that the risk of simultaneous ischemia of both papillary muscles is increased. The great vulnerability of the papillary muscles to ischemic damage is emphasized by the fact that one or both papillary muscles showed evidence of recent or old infarction in 25 per cent of 422 consecutive hearts studied at necropsy.13 During episodes of ischemia or following infarction of a papillary muscle, the muscle is rendered completely or partially incapable of contraction. Providing that the heart is not enlarged, the normal spatial relationships between the elements of the mitral valve apparatus are maintained during isovolumetric contraction and the valve is competent (Fig. 3). However, during ventricular ejection the slack created in the chordae tendineae by the apex-to-base movement of the left ventricle is not taken up because of the inability of the ischemic papillary muscle to shorten (Fig. 3). Thus, a portion of each mitral valve leaflet everts into the left atrium and the valve becomes incompetent. If the ischemia is only transitory, as during an episode of angina pectoris, clinical evidence of mitral valve incompetence rapidly subsides as the ischemic papillary muscle regains the ability to contract. On the other hand, following infarction of a papillary muscle, the clinical

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DePusqmle, and Phillips

ISOVOLUMETRIC

CONTRACTION

MAXIMAL EJECTION

Fig. 3. Papillary muscle dysfunction following infarction or &hernia of the anterolateral papillary muscle. Although the papillary muscle cannot contract (shorten), the mitral valve leaflets remain closed during isovolumetric contraction. However, failure of the papillary muscle to shorten during ejection creates a situation in which the portion of each mitral leaflet supplied by chordae tendineae from the noncontracting papillary muscle everts toward the atrium. The murmur, in this instance, begins after isovolumetric contraction. Ventricular dilatation may modify the characteristics of the murmur (see Fig. 5) (From Burch, DePasquale, and Phillips: Arch. Int. Med. 112:112, 1963).

ISOVOLUMETRIC

CONTRACTION

Fig. 4. Fibrosis and atrophy of the anterolateral papillary valve into the ventricle during isovolumetric contraction atrium during ventricular ejection. The resulting murmur the state of the myocardium (From Burch, DePasquale,

signs of mitral incompetence usually regress slowly as the papillary muscle gradually recovers. The changing characteristics of the murmur associated Jvith papillary muscle dysfunction as a result of infarction of the muscle will be discussed later. It should be pointed out, however, that the sudden development of an apical systolic murmur after myocardial infarc-

tion

is much

more

often

due

to papillary

MAXIMAL EJECTION

muscle is depicted as pulling a portion of the mitral and allowing a portion of the valve to evert into the is variable depending upon the degree of fibrosis and and Phillips: Arch. Int. Med. 112:112, 1963).

muscle dysfunction than to rupture of a papillary muscle or perforation of the interventricular septum. When ischemia and/or infarction results in diffuse scarring, degeneration, and atrophy of a papillary muscle, the retracted muscle pulls a portion of each mitral leaflet into the ventricle so that the valve is incompetent even during isovolumetric contraction (Fig. 4). During

Syndrome of papillary

EARLY SYSTOLE

muscle dysfunction

40.5

LATE SYSTOLE

Fig. 5. Left ventricular dilatation results in centrifugal migration of the papillary muscle away from the atrioventricular orifice with retraction of the mitral leaflets into the ventricle. In addition, both papillary muscles are at a mechanical disadvantage because they must exert tension against intraventricular pressure more tangentially than normally. The murmur begins immediately after the Hurst heart sound because the valve is incompetent during- isovoiumetric contraction. However, it may decrease in intensity during ventricular ejection because of better approximation of the valve leaflets.

ISOVOLUMETRIC

Fig. into

6. Papillary an aneurysm

the

ejection movement permit better

base

CONTRACTION

muscle dysfunction of the left ventricle

resulting (consult

MAXIMAL EJECTION

from the incorporation text) (Arch. Int. Med.

phase of systole, the apex-toof the left ventricle may apposition

of

the

mitral

valve leaflets so that the degree of valve incompetence decreases. Left ventricular dilatation. Left ventricular dilatation is a frequent cause of papillary muscle dysfunction. Under such circumstances the papillary muscles may contract normally, but the spatial relationships between the papillary muscles, the chordae i tendineae, and the A-V orifice ..

of the 112:158,

anterolateral 1963).

papillary

muscle

are altered by the downward and lateral or centrifugal migration of the wall of the left ventricle away from the A-V orifice (Fig. 5). The valve leaflets are thus pulled downward into the left ventricle so that they are incompetent. In addition, the axis of the papillary muscles becomes more oblique with respect to the atrioventricular orifice. Under such circumstances the papillary muscles exert tension on the mitral valve leaflets more tangentially than normally, an obvious me-

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chanical disadvantage. Thus, even when ventricular dilatation is associated with compensatory elongation of the chordae tendineae,i” mitral incompetence may occur. The blowing apical systolic murmur which is often heard in patients with left ventricular dilatation is frequently considered to be due to dilatation of the annulus of the mitral valve. However, because (1) the annulus of the mitral valve consists of dense fibrous tissue which is not easily distended, (2) the surface area of the mitral valve leaflets is about 2.5 times the area of the atrioventricular orifice,5 and (3) the mitral annulus contracts during systole,r5 it would appear unlikely that simple dilatation of the mitral annulus would result in mitral regurgitation. In our opinion, papillary muscle dysfunction is a much more likely explanation for the apical systolic murmur associated with left ventricular dilatation than is dilatation of the mitral annulus. Since the mitral valve leaflets are pulled downward into the left ventricle in the dilated heart, the valve is incompetent during isovolumetric contraction. However, as the left ventricle contracts, the valve leaflets may be brought into better apposition, so that the degree of mitral incompetence decreases as systole progresses (Fig. 5). An exception to the above exists when the papillary muscle is incorporated in an aneurysm of the ventricle. Because of paradoxical movement of the aneurysm outwards during ventricular contraction, the degree of mitral incompetence increases rather than decreases as systole progresses (Fig. 6). Nonischemic atrophy of papillary muscle. Atrophy of a papillary muscle due to ischemic degeneration with fibrosis is a fairly common finding at necropsy., In addition, it is not uncommon to observe atrophy of one or both papillary muscles of the left ventricle in the absence of ischemia in hearts of older patients or in patients who have died of debilitating disease. We have observed many hearts at autopsy in which an atrophic papillary muscle was no larger than the trabeculae carneae. The atrophic papillary muscle exerts excessive traction on the mitral valve leaflets, pulling them downward into the left ventricle so that the mitral

valve is incompetent. Thus, atrophy of one or both papillary muscles must be considered among the causes of mitral incompetence, a fairly frequent finding in older patients. Defective development of the papillary muscle apparatus. We have had little experience with defective development of the papillary muscle apparatus as a cause of the papillary muscle syndrome. Nevertheless, it is obvious that congenitally short or long chordae tendineae, ectopic insertion of the chordae tendineae, or ectopic origin of a papillary muscle would result in alteration of the normal spatial relationships between the various elements of the mitral valve apparatus and in an incompetent mitral valve.n-rs However, as judged from a personal study of over 3,000 hearts at autopsy during the past ten years at the Veterans Administration Hospital in New Orleans, defective development of the papillary muscle apparatus must be a rare cause of mitral incompetence, at least in adult men. Endocardial disease. In endocardial sclerosis of the left ventricle mitral incompetence may develop as a result of involvement of the chordae tendineae and papillary muscles in the fibrotic process so that excessive retraction of the mitral leaflets prevents closure of the atrioventricular orifice during systole.rg It is well known that apical systolic murmurs occur frequently in children with subendocardial fibroelastosis. Levy and Edwardsi have suggested that the mitral incompetence in children with subendocardial fibroelastosis is due to short papillary muscles and chordae tendineae which exert excessive restraint upon the mitral valve leaflets rendering them incapable of firm apposition. Since subendocardial fibroelastosis is often associated with left ventricular dilatation, lateral migration of the papillary muscles must also contribute to the development of mitral incompetence. Heart muscle disease (cardiomyopathy). There is increasing awareness among clinicians and perhaps even among pathologists that there are a group of diseases which involve the heart muscle without affecting other cardiovascular structures. Such diseases have been categorized as primary myocardial disease, heart muscle

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Syndrome of papillary

Fig. 7. Direct fluorescent antibody stain of a papillary muscle of a mouse inoculated with Coxsackie virus Bd. The light areas identify the presence of viral antigen throughout the papillary muscle.

disease, or cardiomyopathy.20v21 Although there is no general agreement on which diseases should be classified as heart muscle disease, some of the diseases presently included in this category may be associated with papillary muscle dysfunction. As already indicated, the papillary muscles perform a great deal of mechanical and metabolic work. It may be for this reason that they are so vulnerable to inflammatory disease. For example, viral myocarditis, which usually has a patchy, often extensively infocal distribution, volves the papillary muscles. Fig. 7 shows the papillary muscle of a mouse inoculated with Coxsackie virus Bq in which viral antigen, demonstrated by direct fluorescent antibody staining, can be identified throughout the muscle. Whether or not a portion of the papillary muscle as shown in Fig. 7 is capable of contraction is unknown. However, it is well known that apical systolic murmurs are often audible during episodes of myocarditis and that such murmurs frequently subside after recovery from the myocarditis.22 Other primary myocardial diseases such as amyloidosis, sarcoidosis, and glycogen storage disease may result in impaired contraction of a papillary muscle for obvious reasons. Disturbances in the time course of papillary muscle activation and contraction. In order to maintain the proper spatial relationships between the various elements of the mitral valve apparatus and the papillary muscle system, not only must

muscle dysfunction

407

the papillary muscles be structurally and functionally normal, but they must also be activated in proper time sequence relative to activation of the free wall and other parts of the left ventricle. The papillary muscles are richly supplied with Purkinje fibers and are activated before the muscle of the free left ventricular wa11.23*24Thus, they are already in a state of tension when the intraventricular pressure increases during isovolumetric contraction so that they are prepared to support the force acting upon the mitral valve. There is a critical relationship between papillary muscle activation and activation of the free wall of the left ventricle. Activation of a papillary muscle too early or too late will result in mitral incompetence. For example, asynchronous contraction of a papillary muscle probably contributes to the mitral incompetence observed during premature ventricular contractions or disturbances in intraventricular conduction of the activating impulse. There are many possible variations in. the timing during the cardiac cycle and the degree of mitral regurgitation, depending upon the time course of papillary muscle activation. Indeed, alterations in the timing of papillary muscle activation relative to free wall activation may be responsible for at least some of the peculiar apical midsystolic sounds which are difficult to explain at present on the basis of the known hemodynamic facts. Rupture of papillary muscle or chordae tendineae. Rupture of a papillary muscle or one or more chordae tendineae results in severe mitral regurgitation because of loss of restraint of the mitral leaflets and eversion of the leaflets into the atrium. However, rupture of a papillary muscle or chorda tendinea is a relatively rare event. Papillary muscle rupture usually occurs in the posteromedial papillary muscle as a result of myocardial infarction and necrosis.25r26 Rupture of a chorda tendinea may occur secondary to bacterial endocarditis, trauma, rheumatic heart disease, or various connective tissue disorders, such as Marfan’s syndrome. Clinicul

manifestations

As already indicated, the time course of mitral regurgitation in patients with the papillary muscle syndrome depends upon

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the nature of the dysfunction. In the discussion of clinical manifestations to follow, emphasis will be given to papillary muscle dysfunction due to ischemic heart disease. However, with knowledge of normal mitral valve function and the underlying disease, the auscultatory manifestations associated with each type of papillary muscle dysfunction can be readily understood. Symptomatology. In general, the papillary muscle syndrome is not associated with specific symptoms, symptomatology being related more to the disease responsible for the papillary muscle dysfunction than to the dysfunction per se. However, particularly in patients with ruptured papillary muscle or chordae tendineae, symptoms related to left ventricular failure may develop directly as a result of the papillary muscle dysfunction. Since ischemic heart disease is one of the most common causes of papillary muscle dysfunction, most patients with the syndrome are past the fourth decade in age. Obviously, any of the manifestations of ischemic heart disease may accompany the papillary muscle dysfunction, including angina pectoris, myocardial infarction, and congestive heart failure, all of which play an important role in the determination of the auscultatory findings. Physicd @zdings. Failure of a papillary muscle to contract during ventricular systole in a patient with a normal or only slightly dilated heart is associated with an apical systolic murmur, the characteristics of which are often unlike those of mitral insufficiency of rheumatic origin. The murmur of rheumatic mitral regurgitation is typically pansystolic and tends to be of uniform intensity (plateau) with possibly minimal late systolic accentuation.27,28 On the other hand, the murmur associated with a “mechanically silent” papillary muscle due to failure of the muscle to contract is often delayed in onset, crescendo-decrescendo in quality (diamondshaped) with midsystolic accentuation (Fig. 8). Thus, it frequently appears to have the qualities of an “ejection” murmur. The tnurmur is soft to moderately loud in intensity and tends to be somewhat “blowing” in quality. It is heard best at the apex, radiates to the axilla, and is only rarely associated with a thrill. The mur-

Fig. 8. Schematic representation of a type of murmur frequently caused by failure of the papillary muscle to contract in the ,absence of left ventricular dilatation or other disturbances of the mitral valve system. Because the spatial relationships among the various elements of the mitral valve apparatus are normal during isovolumetric contraction, the valve is competent during this phase of ventricular systole. However, with the onset of ejection, failure of the papillary muscle to contract results in eversion of a portion of each mitral leaflet into the atrium and mitral insufficiency. Kate that the murmur is “diamond-shaped” or ejection in quality. In this instance, the murmur is depicted as ending before the second heart sound. However, the murmur may be holosystolic depending upon whether or not left ventricular decompensation and/or left ventricular dilatation are present. If the ventricle is significantly dilated, the murmur is earlier in onset, beginning immediately after the first heart sound.

mur is also occasionally xv-e11 transmitted to the aortic area, a finding which when evaluated in the light of the ejection qualities of the murmur may cause some difficulties in differential diagnosis. It should be emphasized that failure of a papillary muscle to contract is not invariably associated with the murmur described above. Myocardial infarction is a frequent cause of a noncontracting papillary muscle and this combination of lesions is commonly accompanied by left ventricular dilatation and congestive heart failure. Under these circumstances the mitral valve leaflets are retracted downward into the left ventricle, so that the murmur begins with the first heart sound. Furthermore, as the ventricles contract, failure of the papillary muscle to contract may actually compensate for the altered spatial relationships between the elements of the mitral valve apparatus so that the valve leaflets come into better apposition as systole progresses and the murmur has a decrescendo quality. A disordered sequence of activation of the

Syndrome

papillary muscles in relation to the other muscles of the left ventricle may also contribute to alterations in the characteristics of the associated murmur. The constancy of the physical findings in a given patient with a noncontracting papillary muscle depends upon the activity of the underlying disease. The murmur accompanying healed infarction or fibrosis of the papillary muscles tends to be constant even over extended periods of observation. In some patients the murmur has been noted to remain virtually unchanged over periods of two to three years. In contrast, during the course of acute myocardial infarction involving the papillary muscles or during episodes of prolonged but fluctuating coronary insuficiency, the murmur may be present for several hours or days, only to disappear completely as the coronary circulation improves and then to return with exacerbation of the coronary insufficiency. The characteristic auscultatory findings of a noncontracting papillary muscle may be present even during transient episodes of angina pectoris. These findings tend to disappear as the attack subsides spontaneously or through the use of carotid sinus pressure or glyceryl trinitrate. Thus, papillary muscle dysfunction due to failure of the muscle to contract and the associated mitral regurgitation may be present as a fixed lesion or may exist as a changing disorder. With the exception of the auscultatory findings, no other physical findings are consistently associated with the papillary muscle syndrome. As might be expected, signs of cardiac enlargement and gallop rhythm (both ventricular and atrial) are frequently observed but are nonspecific with respect to the syndrome. Moderately wide splitting of the two components of the second heart sound at the pulmonic area, which may possibly be related to the degree of mitral regurgitation, is occasionally noted. To the present time, late systolic clicks have not been observed as a feature of the papillary muscle syndrome secondary to acquired ischemic disease. Differentinl diagnosis. The murmur of papillary muscle dysfunction due to failure of the muscle to contract properly

of papillary

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409

must be distinguished from the following entities: (1) mitral regurgitation due to rheumatic valvulitis, (2) aortic stenosis, (3) rupture of the papillary muscle or chordae tendineae; (4) the so-called “late sysand (5) rupture of the tolic murmur,” interventricular septum. It should be pointed out that the demonstration of the rather typical electrocardiographic findings of papillary muscle fibrosis or infarction to be described below is of considerable value in differential diagnosis. Mitral regurgitation due to rheumatic valvulitis may occasionally cause some difficulty in differential diagnosis. A past history of rheumatic fever and a history of onset of the murmur at an early age are of obvious importance in differential diagnosis. As noted above, the murmur of rheumatic mitral insufficiency is characteristically pansystolic and does not have a “diamond-shaped” configuration. It is frequently louder and much more frequently associated with a thrill than the murmur of papillary muscle dysfunction. Helpful ancillary findings in differential diagnosis are the facts that rheumatic mitral insufficiency is associated with a much greater degree of left atria1 enlargement as detected electrocardiographically and roentgenographically and is much more likely to be associated with mitral valve calcification than is mitral insufficiency secondary to papillary muscle dysfunction. It is well established that murmurs of aortic stenosis and mitral insufficiency may masquerade as one another.2g Because the murmur of papillary muscle dysfunction may have an “ejection” quality and may radiate to the aortic area, confusion with the murmur of aortic stenosis can occur. However, the murmur of aortic stenosis tends to be harsher than that of papillary muscle dysfunction. Furthermore, in aortic stenosis the two components of the second heart sound may be only narrowly split or display paradoxical variation with respiration and the aortic component may be reduced in intensity, whereas in papillary muscle dysfunction the two components of the second heart sound are normally or even widely split and the aortic sound is of normal intensity. In the presence of atria1 fibrillation, the

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murmur of aortic stenosis tends to be more accentuated following a long diastolic pause30 than is the murmur of mitral insufficiency due to papillary muscle dysfunction. The amyl nitrate tesP may be of value in distinguishing between the murmur of aortic stenosis and that of mitral regurgitation In this test, careful auscultation and/or phonocardiography is carried out while and immediately after the patient inhales amyi nitrate. The murmur of papillary muscle dysfunction becomes softer during and approximately 20 seconds after inhalation of amyl nitrate, whereas the murmur of aortic stenosis becomes louder, reaching a peak intensity approximately 30 to 4.5 seconds after inhalation. Additional clinical data such as onset of the murmur at an early age, exertional syncope, narrow pulse pressure, slow rising pulse of small volume, demonstration of calcium in the aortic valve or root, and poststenotic dilatation of the aorta favor the diagnosis of aortic stenosis rather than papillary muscle dysfunction. Rupture of the mitral valve, of the chordae tendineae, or of a papillary muscle results in a loud apical systolic murmur which is often of ejection type or “diamond-shaped. “B-~~ This murmur may radiate to the aortic area where it may be confused with the murmur of aortic stenosis. It is most important to distinguish between the murmur of papillary muscle dysfunction due to rupture of the mitral valve, chordae tendineae, or papillary muscle and the murmur of papillary muscle dysfunction due to infarction or ischemia of a papillary muscle without loss of continuity among the various elements of the mitral valve apparatus. Under both sets of circumstances, the murmur may be loud, ejection in type, and associated with wide splitting of the second heart sound. In addition, infarction of a papillary muscle with rupture results in electrocardiographic alterations similar to those of infarction of a papillary muscle without rupture. Thus, distinction between mitral insufficiency due to papillary muscle dysfunction with and without loss of continuity among the various elements of the mitral valve apparatus may occasionally be difficult. Nevertheless, rupture of either a papillary muscle or the chordae tendineae

usually results in rapid deterioration of the clinical state of the patient, with congestive heart failure and death often occurring within 24 hours. Such a sudden and dramatic demise does not occur in the papillary muscle syndrome. Although the murmur associated with rupture of a papillary muscle or of chordae tendineae may be “diamond-shaped” and have a midsystolic accentuation, unlike the murmur of papillary muscle dysfunction without loss of continuity, it tends to be early in onset, may be associated with a thrill,3S and is usually very loud and holosystolic. The so-called late apical systolic murmur has been a source of great interest recently.36-46 These murmurs are mostly confined to the latter part of systole, at which time they assume a crescendo or crescendo-rapid decrescendo configuration. They are frequently but not invariably associated with one or more mid-to-late systolic clicks (nonejection type). Their origin was originally thought to be extracardiac, perhaps from old pericarditis38z43; but more recently it has generally been agreed that most, if not all, are associated with some degree of mitral insufficiency.3g-41 The exact defect involved is not yet well delineated, but abnormalities of the papillary muscle, chordae tendineae, and/or mitral leaflets have been suggested. There is good evidence that, in some instances, the defect responsible for the murmur is congenital in origin with familial propagation.36 The occurrence of such a murmur in Marfan’s syndrome has been noted.36s44s45 The typical murmur has been shown to be temporally related to angiocardiographicallydemonstratedmitralregurgitation.36~3g~41 It has been suggested that the systolic click frequently associated with the late systolic murmur is due to sudden tensing of slack chordae tendineae (“chordal Snap”)36’46 and hence the term “nonejection” click. Angiocardiography in patients with the late apical systolic murmur has not only demonstrated mitral regurgitation but has also displayed abnormal “doming” or “bulging” of the posterior (septal) mitral leaflet40~41 and even aneurysmal protrusion of the leaflet.36 It is of interest that a number of patients with late systolic murmurs have chest pain and electrocardiographic ab-

Volume Number

75 3

Syndrome of papillary

normalities consisting of ST-segment depression and T-wave inversion in Leads II, III, aVF, V5, and Vg, and peaked, tall T waves in the midprecordial leads (V, to VJ.36J*,4r It is in this group, especially, that the possibility of ischemic papillary muscle dysfunction as an etiologic factor might be raised. However, Barlow and Bosman36 have suggested that abnormal mitral valve function is more likely the cause of the murmur than ischemic disease.36 Although it is yet to be demonstrated, these authors postulated that aneurysmal dilatation of the posterior mitral leaflet distorts the circumflex coronary artery, thereby resulting in the ischemic features of the disorder. Although there are superficial similarities, mitral insufficiency of the type associated with the late systolic murmur should not be confused with the insufficiency due to ischemic papillary muscle dysfunction. For, in the latter, the murmur is usually (but not invariably) loudest in midsystole and typically is not associated with systolic clicks. Because of its occurrence in association with acute myocardial infarction, rupture of the interventricular septum must be considered in the differential diagnosis of papillary muscle dysfunction. Septal rupture is not an extremely rare complication of myocardial infarction.47-51 Rupture of the interventricular septum usually leads rapidly to congestive heart failure and early death. There is usually both left and

Fig.

9. ECG

displaying

Type

I alterations

in ischemic

muscle dysfunction

411

right ventricular failure, frequently with evidence of tricuspid insufficiency. The associated systolic murmur may be accompanied by a thrill and is most intense in the fourth left intercostal space close to the sternum. Although the murmur may be “diamond-shaped” in configuration, it is usually holosystolic in timing and duration. If the above characteristics are kept in mind, confusion with papillary muscle dysfunction can usually be avoided. Electrocardiographic differences may be of further aid in differential diagnosis. Electrocardiography

Although papillary muscle dysfunction may be the result of a number of disease (ECG) processes, the electrocardiogram has been studied in detail only in papillary muscle dysfunction secondary to circulatory insufficiency.3 Electrocardiographic criteria for the recognition of infarction and/or fibrosis of the papillary muscles have been confirmed at autopsy. The criteria for diagnosis of anterolateral papillary muscle involvement have been presented in detail elsewhere,3 and preliminary data on the recognition of posteromedial muscle involvement have been mentioned.2 Since these publications, additional data have been accumulated. Studies of infarction or fibrosis of the anterolateral papillary muscle have delineated electrocardiographic changes of three basic types with some overlapping between types. Type I consists of mod-

disease

of the

papillary

muscle

(consult

text).

erate depression of junction J, with concavity-upward or slight convexity-downward deformity of the ST-T interval (Fig. 9). Type II consists of slight to moderate depression of junction J but with a prominent convexity-upward deformity of the ST-T interval and terminal inversion of the T wave (Fig. 10). Type III consists of marked depression of junction J, usually associated with a slight convexity-upward (occasionally concavity-upward) deformity of the initial ST-T interval (Fig. 11). In general, the Type I pattern is associated with chronic fibrosis of the papillary muscle, Type II with prolonged ischemia of the papillary muscle, and Type III with

Fig.

IO. ECG

displaying

Fig.

11. ECG

displa)

Type

ilxg Type

II alterations

111 alterations

in ischemic

in ischemic

acute circulatory insufficiency or infarction of the papillary muscle. It should be emphasized that prolongation of the QT interval and T-U segment or U wave abnormalities are extremely common in each of the three electrocardiographic types. In anterolateral papillary muscle the electrocardiographic involvement, changes described above occur predominately in Leads I, a\;1 , 175, and Vg; whereas in posteromedial papillary muscle involvement, these changes are found predominately in Leads II, III, aVF, and/or 111 through Vq. Because involvement of both is not unusual, there papillary muscles may be overlapping of the findings. Fur-

disease

d;sease

of the papillary

of the

papillary

muscles

muscles

(consult

(consult

text’).

test).

Syndrome of papillury

thermore, it should be noted that detailed electrocardiographic studies have been carried out only in ischemic papillary muscle dysfunction, and there is a need for such studies in other types of papillary muscle involvement. Although the electrocardiographic changes described above are not pathognomonic of ischemic disease of the papillary muscles, their predictive value, as determined at autopsy, has proved to be remarkably accurate. As pointed out before, 1iowever,3 one or especially a combination of the following could lead to difficulty in interpretation: left ventricular hypertrophy, the shock syndrome (especially if treated with potent vasopressor agents), subendocardial infarction or hemorrhage not necessarily involving a papillary muscle, digitalis and quinidine (or procaine amide) effect, post-tachycardia syndrome, coronary insufficiency, severe disturbance of intraventricular condition, and electrolyte imbalance. Somewhat surprisingly, these factors have rarely proved troublesome except in the presence of extreme left ventricular hypertrophy associated with either severe diastolic hypertension or severe aortic valvular insufficiency. In these clinical states the Type I or Type II electrocardiographic pattern of papillary muscle involvement may be simulated. Electrocardiographic evidence of severe left ventricular hypertrophy and dilatation is usually superimposed, however, and is of aid in differential diagnosis. It should be noted that only a little more than half of the patients with typical electrocardiographic findings of papillary muscle fibrosis or infarction will have the characteristic auscultatory features of the syndrome. Furthermore, there is no doubt that the physical findings of papillary muscle dysfunction may occur in the absence of typical electrocardiographic changes, but the frequency of this occurrence has not yet been tabulated. Other

luborutory

data

Phonocardiography has confirmed the auscultatory features of papillary muscle dysfunction as outlined above. Because a large majority of patients with this disorder have serious ischemic heart disease, few hemodynamic studies are available.

muscle dysfunction

413

Holloway and associates”” recently reported data obtained by right and left heart catheterization in two patients with papillary muscle dysfunction. Of course, of great interest was their confirmation of mitral insufficiency by cinefluorography and indicator dilution studies. Summary The function of the papillary muscles to restrain the mitral valves is obvious. However, the dynamic nature of this function is not always appreciated. Failure of one or both papillary muscles to shorten during the ejection phase of ventricular systole, fibrosis, and atrophy of a papillary muscle or centrifugal migration of the papillary muscles due to left ventricular dilatation result in mitral incompetence. Depending upon the etiology of the papillary muscle dysfunction, apical systolic murmurs of varying characteristics may be heard. In general, a noncontracting papillary muscle in a normal-sized heart is associated with a murmur which is late in onset and crescendo-decrescendo in quality, whereas in the dilated heart the murmur is early, beginning with the first heart sound, and may be decrescendo, plateau, or crescendo-decrescendo in quality. Obviously, the murmurs of papillary muscle dysfunction may vary considerably depending upon the nature of the dysfunction and time course of activation of the muscle and other portions of the ventricular musculature. Associated electrocardiographic abnormalities may also ocMitral insufficiency due to acquired or congenital valvular disease has been exhaustively studied. On the other hand, mitral insufficiency secondary to disease of the papillary muscles has been almost completely neglected. Nevertheless, since our description of the papillary muscle syndrome in 1963,l more than 20 papers dealing directly or indirectly with this syndrome have appeared. In the present review we have extended the original description of the papillary muscle syndrome to include a number of diseases which either clinically or at necropsy have been implicated in the production of papillary muscle dysfunction in the hope that attention will be focused on those

414

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Burch, DePasquale, and Phillips

diseases, in addition to circulatory insufficiency, which may result in papillary muscle dysfunction. REFERENCES Burch, G. E., DePasquale, N. P., and Phillips J. H.: Clinical manifestations of papillary muscle dysfunction, Arch. Int. Med. 112:112, 1963. J. H., Burch, G. E., and DePasquale, 2. Phillips, N. P.: The syndrome of papillary muscle dysfunction. Its clinical recognition, Ann. Int. Med. 59:508, 1963. J. H., DePasquale, N. P., and Burch, 3. Phillips, G. E.: The electrocardiogram in infarction of the anterolateral papillary muscle, An{. HEART J. 66:338, 1963. 4. Estes, E. H., Jr., Dalton, F. M., Entman, M. L., Dixon, H. B., II, and Hackel, D. B.: The anatomy and blood supply of the papillary muscles of the left ventricle, AA~. HEART J. 71:356, 1966. R. C.: The surgical and pathological 5. Brock, anatomy of the mitral valve, Brit. Heart J. 14:489, 1952. M. A., Lees, W. M., and Thompson, 6. Chiechi, R.: Functional anatomy of the normal mitral valve, J. Thoracic Surg. 32:378, 19.56. R. F., Finlayson, B. L., and Nash, 7. Rushmer, A. A.: Movements of the mitral valve, Circulation Res. 4~337, 1956. 8. Davila, J. C., and Palmer, T. E.: The mitral valve, Arch. Surg. 84:174, 1962. S. K.: Mechanism of the movements 9. Brockman, of the atrioventricular valves, .4m. J. Cardiol. 17:682, 1966. G. E., and DePasquale, N. P.: Time 10. Burch, course of tension in papillary muscles of the heart, J.A.M.A. 192:701, 1965. 11. Puff, von A., Barrenberg, M., and Goerttler, T.: Rijntgenkinematographische Untersuchungen iiber den Bewegungsmechanismus der Mitralklappe, Fortschr. Geb. RGntgenstrahlen. 102: 607, 1965. 12. Burch, G. E., Ray, C. T., and Cronvich, J. A.: The George Fahr Lecture: Certain mechanical peculiarities of the human cardiac pump in normal and diseased states, Circulation 5:504, 1952. N. P., and Burch, G. E.: The 13. DePasquale, necropsy incidence of gross scars or acute infarction of the papillary muscles of the left ventricle, Am. J. Cardiol. 17:169, 1966. 14. Edwards, J. E., and Burchell, H. B.: Pathologic anatomy of mitral insufficiency, Proc. Staff Meet. Mayo Clin. 33:497, 1958. 1.5. Smith, H. L., Essex, H. E., and Baldes, E. J.: A study of the movements of heart valves and of heart sounds, Ann. Int. Med. 33:13.57, 1950. 16. Actis-Dato, A., and Milocco, I.: Anomalous attachment of the mitral valve to the ventricular wall, Am. J. Cardiol. 17:278, 1966. M. J., and Edwards, J. E.: Anatomy of 17. Levy, mitral insufficiency, Progr. Cardiovas. Dis. 5:119, 1962. 18. Shone, J. D., Seller, R. D., Anderson, R. C.,

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Adams, P.? Jr., Lillehei, C. W., and Edwards, J. E.: The developmental complex of “parachute mitral valve,” supravalvular ring of left atrium, subaortic stenosis, and coarctation of aorta, Am. J. Cardiol. 11:714, 1963. Van Buchem, F. S. P., Arends, A., and Schroder, E. A. : Endocardial fibroelastosis in adolescents and adults, Brit. Heart J. 21:229, 1959. Burch, G. E., and Walsh, J. J.: Cardiac insufficiency in chronic alcoholism, Am. J. Cardiol. 6:864, 1960. Mattingly, T. W.: Clinical features and diagnosis of primary myocardial disease, Mod. Cont. Cardiovas. Dis. 30:677, 1961. Burch, G. E., and DePasquale, N. P.: Viral myocarditis, in Ciba Foundation Symposium on Cardiomyopathies, London, 1964, J. & A. Churchill, Ltd:, p. 376. Durrer, D., and Tweel, L. H. van der: Excitation of the left ventricular wall of the dog and goat, Ann. New York Acad. SC. 65:779, 1957. Lev, M. : The normal anatomy of the conduction system in man and its pathology in atrioventricular block, Ann. New York Acad. SC. Ill:81 7, 1964. Smith, J. C.: Rupture of a papillary muscle of the heart; report of two cases, Circulation 1:766, 1950. Robinson, J. S., Stannard, M. M., and Long, M.: Ruptured papillary muscle after acute myocardial infarction, Afir. HEART J. 70:233, 1965. Leatham, A.: Aurcultation of the heart, Lancet 2:703, 1958. Phillips, J. H., and Burch, G. E.: Selected clues in cardiac auscultation, A&I. HEART J. 63:1, 1962. Burch, G. E., and Phillips, J. H.: Murmurs oi aortic stenosis and mitral insufficiency masquerading as one another, A&t. HEART J. 66:439, 1963. Henke, R. P., March, H. W., and Hultgren, H. N. : An aid to identification of the murmur of aortic stenosis with atypical localization, AX HEART J. 60:354, 1960. Vogelpoel, L., Nellen, M., Swanepoel, A., and Schire, V.: The use of amyl nitrate in the diagnosis of systolic murmurs, Lancet 2:810, 1959. Shapiro, H. A., and Weiss, D. R.: Mitral insufficiency due to ruptured chordae tendineae simulating aortic stenosis, New England J. Med. 261:272, 1959. Case records of Massachusetts General Hospital, New England J. Med. 267:1033, 1962. Osmundson, P. J., Callahan, J. A., and Edwards, J. E.: Mitral insufficiency from ruptured chordae tendineae simulating aortic stenosis, Proc. Staff Meet. Mayo Clin. 33:235, 1958. Holloway, D. H., Whalen, R. E., and McIntosh, H. D.: Systolic murmur developing after myocardial ischemia or infarction, J.A.M.A. 191: 888, 1965. Barlow, J. B., and Bosman, C. K.: Aneurysmal protrusion of the posterior leaflet of the mitral valve. An auscultatory-electrocardiographic syndrome, AM. H&ART J. 71:166, 1966. Barlow, J. B.: Conjoint clinic on the clinical

Syndrome of pupillauy

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44.

significance of late systolic murmurs and nonejection systolic clicks, J. Chronic Dis. 18:665, 1965. Humphries, J. O., and McKusick, V. A.: The differentiation of organic and “innocent” systolic murmurs, Progr. Cardiovas. Dis. 5:152, 1962. Barlow, J. B., Pocock, W. A., Marchand, P., and Denny, M.: The significance of late systolic murmurs, Au. HEART J. 66:443, 1963. Segal, B. L., and L&off, W.: Late systolic murmur of mitral regurgitation, AM. HEART J. 67:757, 1964. Tavel, M. E., Campbell, R. W., and Zimmer, J. F. : Late systolic murmur and mitral regurgitation, Am. J. Cardiol. X:719, 1966. Leatham, A.: The value of auscultation in cardiology, Arch. Int. Med. 105:349, 1960. McKusick, V. A. (ed.): Symposium on cardiovascular sound. II. Clinical aspects, Circulation 16:414, 19.57. Segal, B., Kasparian, H., and Likoff, W.: Mitral regurgitation in a patient with the Mar-fan syndrome, Dis. Chest 41:457, 1962.

4.5.

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Bowers, D. : An electrocardiographic pattern associated with mitral valve deformity in Marfan’s syndrome, Circulation 23:30, 1961. Reid, J. V. 0.: Mid-systolic clicks, South African M. J. 35:353, 1961. Bond, V. F., Jr., Wefare, C. R., Lide, T. N., and McMillan, Ii. L.: Perforation of interventricular septum following myocardial infarction, Ann. Int. Med. 38~706, 1953. Harrison, R. J., Shillingford, J. P., Allen, G. T. and Teare, I).: Perforation of interventricular septum after myocardial infarction, Brit. M. J. 1:1066, 1961. Sanders, R. J., Kern, W. H., and Blount, S. G., Jr.: Perforation of interventricular septum complicating my-ocardial infarction, AAS. HEART J. 51:736, 1956. Lee, W. Y., Cardon, L., and Slodki, S. J.: Perforation of infarcted interventricular septurn, Arch. Int. Med. 109:731, 1962. ^ Pavne. W. S.. Hunt. T. C.. and Kirklin. T. W.: Surgical repair of ventricular septal defect due to myocardial infarction, J.A.M.A. 183:603, 1963.