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A reappraisal of papillary muscle dysfunction
A Reappraisal Muscle
of Papillary
Dysfunction*
Correla tiue Clinical and Angiographic JAMES C. SHELBURNE,
M.D.,?
DOROTHY
RUBINSTEIN,
M.D.
Stu&
and RICHARD
GORLIN,
M.D.
Boston, Massachusetts Fourteen patients with mitral insufficiency due to papillary muscle dysfunction and fifty control subjects with coronary atherosclerosis but no mitral insufficiency were evaluated clinically and studied by right and left heart catheterization, selective coronary arteriography and left ventricular cineangiography. The murmur of this condition was found to vary in timing from early to late systole or to be holosystolic; the site, radiation and intensity of the murmur were inconstant. These features bore no relation to the degree of angiographically visualized mitral insufficiency, but there was precise correlation between timing of onset of regurgitation by ventriculography and timing of the murmur within systole. Seven of the control subjects who had murmurs clinically indistinguishable from the patient group did not have angiographically demonstrable mitral regurgitation. No characteristic electrocardiographic pattern was found nor could specific papillary muscle group involvement be distinguished angiographically. All patients had three vessel coronary artery disease, but with an increased incidence of severe right coronary artery lesions. Abnormal left ventricular systolic contraction was found in all but one of the patient group. The hemodynamic abnormalities such as markedly reduced cardiac output may be as much due to the left ventricular asynergy as to the mitral incompetence. This factor deserves full consideration if corrective surgery of the valvular lesion is contemplated.
A
correlate with the presence and severity of the mitral insufficiency? (3) What is the pathophysiology of the lesion? (4) What are the associated coronary artery lesions? (5) What is the prognosis of this condition?
LTHOUGH the acute and chronic syndromes of papillary muscle dysfunction have been described before [I-83, there is no report in which the coronary arterial anatomy and the nature of the valvular incompetence have been studied during life by angiographic technics. In this study the clinical, hemodynamic and angiographic findings were analyzed in fourteen patients with mitral insufficiency due to
MATERIAL The fourteen patients here described were seen in our laboratory during the past three years (19651968) because of either angina pectoris or congestive heart failure. The criteria for inclusion in the study were as foIlows: (1) The existence of a systolic murmur and demonstration of mitral insufficiency by angiography. (2) The absence of (a) all stigmata of rheumatic heart disease, (b) congenital
papillary muscle dysfunction. The study was undertaken with the following questions in mind: (1) Are there any characteristic clinical features which allow this diagnosis to be made? (2) How do the characteristics of the murmur
* From the Cardiovascular Unit, Department of Medicine, Peter Bent Brigham Hospital and Harvard Medical School. This study was supported by U. S. Public Health Service Grants 5RO1-HE08591-04, TTOl-HE05679-03, lPOl-HEI 1306-01 and the Kriendler Memorial Foundation. Requests for reprints should be addressed to Richard Gorlin, M.D., Cardiovascular Unit, Peter Bent Brigham Hospital, 721 Huntington Avenue, Boston, Massachusetts 02115. Manuscript received June 17, 1968. t Postdoctoral Trainee, National Heart Institute, U. S. Public Health Service. Present address: Department of Medicine, University of California School of Medicine, The Center for the Health Sciences, I-OS .4ngeles, California 90024.
862
AMERICAN
JOURNAL
OF
MEDICINE
Muscle
Papillary
lIysfunc%iorlTABLE
C.L,NIC:AL
I 2
J.G W.(1.
.i;. ;3,
!bl \I
3 4
L.hl. A.7
52, \I
I’rrarni l’rrsmt 5 VT. Non.?
FEATURES
Norm.11 52 hid
110!70
lf
Normal
Normal
N0n.Z NOW
11 o/70 120/90
Not remarkable Bitid. 4f
Soft Normal
N0rm.Xl Fixed sphl
s1; s, Sr
11.x.
42, F
MR. A.S.
-59, \I ;4. hf
11
R.!V.
4‘,
12
.I.\I.
lJ8.11
13
Y.1 ;.
73, F
14
N \I.
bi. F
2 \7. 3 yr.
NOW
140/90 125/80
Diff
18O,e30 140 ‘90
Not rcmwk., hlr
1+
1 yr.
?
NOX
120,‘70
1+
Normal
Norm.il
None x \r.
2 mo. ?
1 yr. None
lGO/lOO 115/70
Not rcmd.rk,ible Bifid impulsr
Normal Normal
Nnne
2 yr.
2 ?P.
130,‘lOO
3+
Soft
Normal F’aradoxical split with angina attack Reversed split
Ii yr. ’ 2 yr. 6 yr.
2 yr.
7 yr.
120/70
Not remarkable
Normal
Normal
?
None
130,/80
Bilid
N0IIllal
NO~lTl‘Il
5 )r. 2 yr.
3 yr.
None
120/‘70
Nor remarkable
Normal
Normal
Sa, ,5r s:
s,
SI Intermilrenc
SI
mfarcr.
heart disease, (c) bacterial endocarditis, (d) history of chest trauma, (e) idiopathic hypertrophic subaortic stenosis. The diagnosis was confirmed at either operation or necropsy in five patients. The subjects in the series ha\e been followed for six to thirty-two months at the time of writing. Fifty patients studied in similar fashion during the same time period served as controls. Each was shown to have coronarv atherosclerosis but no mitral insufficiency by yen&culography. METHODS
All patients were admitted to the hospital, were seen by one or more of us and underwent left and right heart catheterization. The evaluation of each patient included chest roentgenogram (four views with barium swallow)). electrocardiogram and phonocardiogram. Alurmurs were graded in intensity from 1 to 6. Pressures were inscribed on a Sanborn No. 560 polybeam photographic recorder using a Statham P23D transducer. Cardiac outputs were measured by means of indocyanine green dye and a Gilford densitometer. Selective cineangiography of the coronary arteries was performed in multiple projections by the Soncs technic [9]. IIford Pan F 16 mm. film was used and the angiograms were registered by means of either a 6 inch or a dual-field General Electric image amplifier. The studies were reviewed by at least two of us independently and all films were of high diagnostic quality [lOI. Disease in a coronary arteq was consideied significant when stenosis was greater than 75 per cent of the lumen JCXE
Normal Loud
ixone
9 10
46,
Fixed split Pz loud
6 mo. 3 yr.
R
VOL.
Soft LOWi
?
;v. hl 35. hi
myocardial
2 +
10 yr. ?
A.K.
* Diaptnlgmatic
DYSFUNCTION
N0ll.Z
G.1.. w 1.
Prwnr II \r. Prrwit I, ,r.
MCSCLE
Present ? duration 1 yr. NOW
.5
Pn sent 5 \r. NO”?
PAPILLARY
5 yr. 3 yr.
6 7
\I
I
WITH
10 yr.* 5 yr.
<,I,51 l’rrsmt 14 yr. c \r. 3 yr. 2 7. 5’).51 Pmcnt None 4 w. Prrscn1 Prcsenr 3 yr. Prcsrni 7 \r. K
OF PATIENTS
x0 ?
.YMi~.tr-r/c’rt 01.
1969
diameter. Ventriculography was performed at rest in all patients, with power injections of 40 to 60 ml. of 75 per cent Hypaque@ into the left ventricle via a No. 7 or No. 8 Lehman catheter. Film speed was 60 frames per second and one or two projections were used, including the right anterior oblique. Each ventriculogram was interpreted qualitatively for uniformity of contraction at all points along the inner ventricular surface, as well as for the ventriclelar chamber size, shape and wall thickness [Ill. Only normally conducted beats were selected for study. A qualitative estimate of the severity and time of occurrence of mitral regurgitation was made in each case. RESULTS
The clinical features of the patients are summarized in Tables I, II and III. Eleven of the fourteen patients were male, Clinical
Features.
their ages ranged from thirty-three to sixtyeight years. All but two of our patients gave a history of angina which had been present for up to ten years. Five of the fourteen patients had clinically overt heart failure. Ten gave a definite history of prior myocardial infarction. The murmur had been present, when known, for a period rarqing from two months to ten years. In several patients the murmur was first heard following an acute myocardial infarction.
864
Papillary
Muscle Dysfunction-Shelburne
et al.
TABLE II ELECTROCARDIOGRAPHIC FEATURESOF PATIENTSWITH PAPILLARY MUSCLEDYSFUNCI’ION
ChSe No. Patient
Left Ventricular HyperRhythm
Axis
trophy
Left Atrial EnIargement
NAD
Present
Present
RAD NAD
Present Present
Present
1
J.G.
2 3
W.G. L.M.
NSR PR = 0.22 sec. NSR NSR
4
A.T.
NSR
NAD
5
A.E.
NSR
LAD
6
G.L.
NAD
7 8 9 10 11
W.A. H.K. M.R. A.S. R.W.
LAD NAD LAD NAD NAD
12
J.M.
NSR VPB’s NSR NSR NSR NSR NSR PR = 0.23 sec. NSR
13
F.G.
NSR
LAD
14
N.M.
NSR
LAD
ST-T Abnormalities
Myocardial Infarct*
Conduction Defcctt IVCD
T 1 II,’ ;;I, AVF .I depression in vz-v, T flat I, AVL, V6_V6 T flat throughout tracing ST-T _1I, II, AVL, V4-V,
Present
. Present
IVCD ST 4 I, ;I,’ Vg-VB I&B T -1 II, ;;I.,
AVF
.
NAD
, .
T&I,AVLSTt with V2-V, T _1II, II-I, AVF, Vs-Vs
Old%MI Old .1MI Possible old DMI Old AM1
IVCD
Possible old ASMI
NOTE: NSR = normal sinus rhythm. NAD = normal axis deviation, i.e., $30” to +90”; L:\D = left axis deviation, i.e., +30” to -30“; RAD = right axis deviation, i.e., >+90”. * AM1 = anterior myocardial infarct; DMI = diaphragmatic myocardial infarct; ASMI = anteroseptal myocardial infarct. t IVCD = intraventricular conduction defect; RBBB = right bundle branch block.
The apical impulse was left ventricular in character in nine of fourteen patients and frequently it was diffuse or bifid suggesting ventricular aneurysm. A third or fourth heart sound was heard in six of fourteen patients. Only two patients had a palpable systolic thrill. The systolic murmur was of moderate (grade 3 to 4) intensity in eight patients and grade 2 in the remaining six. In five patients the murmur was holosystolic; in two, late systolic; in seven, either early or mid-systolic in timing. The murmur was usually heard at the apex and lower left sternal border and it radiated to the axilla. In no patient was the murmur heard in the neck. Electrocardiography. The electrocardiographic changes are outlined in Table II. All patients were in normal sinus rhythm. No specific electrocardiographic pattern was seen in this group. Evidence of prior myocardial infarction was noted in six, left ventricular hy-
pertrophy [f2] in five and nonspecific Sl‘-T abnormalities in eight. Roentgenography. The heart was enlarged due to enlargement of the left ventricle in eight patients. The right ventricle was prominent in three. The left atrium was enlarged in only four. The lung fields were unremarkable in all patients. Reflux of dye into the Ventriculography. left atrium from the left ventricle occurred in all patients. In Table III the timing of the murmur during systole is compared with the time of appearance of dye into the left atrium. Although there was no correlation with the radiation or character of the murmur, there was excellent agreement between the appearance time of mitral regurgitation and the clinical timing of the murmurs. There was no uniform correlation between the amount of regurgitation and the intensitv of the murmur. Paradoxical systolic expansion of the opacified left
Muscle Dysfunction-m -,Shrltwnr
Papillary
Lelt I’dtKUI
\‘e”tric~d.rr Motion*
.I.(:.
‘>OTO npiwl
1V.c:
Marked
L.hl.
Diffusr
.~“r,q
Regirgitatio”
~“3
3+,
hypohinesis hypokincsis
4f
.?.I
3f
%.R.
Norm.,1
G.L.
Large
W.A.
Akinesis, ;~“terolateral wall Large apical aneurysm Generalized hypokinesis
1i.K. M.R. A.S.
J.M. F.G. N.M.
Apical aneurysm Apical paradox hypokinesis
=
generalized
with systole systolic
Grade
4
Grade
1
Soft
elirly
Grade
4
Deacend~
Grade
3
severe, systolic moderate,
latesystolic
I to
3 to 4+,
early
Grade
2
Grade
2
Soft
Grade
3
Soft
Grade Grade
2 3
Soft
Grade
2
Grade
4
Ejection
syst0le 2+,
early systole
Grade
4
1 f,
early systole
Grade Grade
2 2
3+, early systolic
inferior
reduction
e.ml)
E.wly
Intensity
3+, mid to late systole 1 to 2+, early to mid systole 3+, “ondiagnostic I+, early systole 2+, early systale I+, early systole
aneurysm
Inferior and apical aneurysm and akinesis Aneurysm, anteroapical B of left ventricle Generalized hypokinesis
R.W.
* l-fypokinesia
contraction apical
early,
onsetof
3+,
in normal
holo-
degree
of contraction;
Soft
nkinesis
TABLE RESULTS
OF CORONARY
ARTERIOGRAPNY
Coronary Patient
Dominance
J.G. W.G. L.M. A.T. A.R.
R R L R R
G.L.
R
W.A.
R
l3.K.
R
M.R.
R
A.S.
I.
* L.41)
=
90 y0 stenosis Proximal 50% stenosis Proximal 90 7: stenosis 90% stenosis 75 y0 stenosis of 1st diagonal branch 75 “ib stenosis of main LCA Narrow 1st diagonal branch 75% stenosis distal to 1st diagonal branch Intramural disease; 100% stenosis of 1st diagonal branch Proximal 100%
R
Proximal
J.M.
R
LCA
1; G.
R
Proximal loo%;, 1st diagonal branch 755 xc“osia 75 cc stenosis
iefr anterior
R
descending:
Artery*
75 y0 stenosis
100%
I.(:F
=
left circomHex:
=
local
absence
of wall
motion.
IV
1N PATIENTS
LAD
R.W.
A.M.
et al.
Lesions
WITH
PAPILLARY
MUSCLE
DYSFUNCI‘ION
C:l&iter&
(Stenosis)
LCF
Proximal 50 Y0 stenosis Proximal 90% stenosis Intramural disease Intramural disease 30y0 stenosis of marginal branch Proximal 907‘ stenosis
Proximal 100%
90%
None Nonr None Non,.
strnosis
,.
NOX”d
95 70 stenosis Mid 1007,
Right
90 yc stenosis
Lefr
LCA calcium nondiagnostic Marginal 90% stenosis
Intramural disease, distal 50% stenosis Proximal 75’“, stenosis
Leh
75y0 stenosis, 1st mxginal circumflex
ProYimnl
8OZ
lOO?E of posterior descending 50% stenosis of 1st marginal circumflex 50 y0 stewxs
Proslmal
loo”;
Mid
90 $
stenosis
Proximal
TU
From
RCA
Proxim.d
RCA
=
nsh~
coromw
100”;
;
Proximal 75 ‘;i, mid 100% marginal 9Opb stenosis Normdl
Proximal
;wterx
loo’:
Smt
stenosib
Left Richt L& Ixtr Riqht
Right Left Right Let-c Right .eft
I
Right Lefr
Left
Right Left
Left Right
I.eT1
866
Papillary
Muscle
et al.
Dysfunction-Shelburne
TABLE v HEMoDYNAMIcsOF PATIENTSWITH PAPILLARY MUSCLE Case NO. __-_ 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Patient J.G. \Y.G. L.M. A.T. AK. G.L. \Y.!\. H.K. M.R. N.S. R.\V. J.M. F.G. N.M.
PA s/d
RV s/d
R.4,
PC,
5;;; 53/2 30/8
1 1 2 5
‘Zj
4;;;9 55/21 25/11 78/34 60/30
7j;13 60/3
‘S 6
‘%
3%
‘.’4
23 10
‘i,
LV s/d 106/25 136/6 99/10 107/12 138,‘20 175/54 127/36 110/12 184/12 120/3 115/12 97/26
72/34 8
133/20 124/15
DYSFUNCTION
sep/SEP
SER
CI
SI
BA s/d
0.24/23 0.25/19 0.24/20 0.32/19 0.32/19 0.30/22 0.22/26 0.28/24 0.30/23 0.40/19 0.20/18 0.22122 0.28/25 0.28/24
79 92 85 97 144 58 68 100 110 74 45 64 153 68
1.8 1.7 2.1 1.8 2.7 1.3 1.6 2.6 32 1.4 .79 1.4 2.4 1.4
19 23 22 31 46 17 14 28 41 29 9 14 25 16
105/72 167/73 103/57 1 lo/64 133/71 174/88 120/90 122/70 190/83 133/72 87/67 119/65 136/80 123/75
NOTE: Pressures are recorded in mm. Hg. PA = pulmonary artery; RV mean; PCm = pulmonary capillary wedge mean; LV = left ventricle; sep beat); SEP = systolic ejection period (seconds per beat per minute). SER = per systolic second per meter squared). CI = cardiac index (L. per minute (cc.per minute per meter squared). B.4 = bra&al artery.
= right ventricle; RAm = right atria1 = systolic ejection period (seconds per systolic ejection rate (cubic centimeters per meter squared). SI = stroke index
atria1 chamber was noted in five of the fourteen patients. Coronary Arteriogra@y. Twelve of the fourteen patients in the study group had right dominant coronary circulation.* The incidence of severe stenosis of each of the coronary arteries is shown in Table IV. The right coronary artery was affected in twelve of fourteen patients, the left anterior descending in ten and the left circumflex in seven. Hemodynamics (Table V). Seven of our fourteen patients had left ventricular enddiastolic pressure (LVedp) greater than 12 mm. Hg; each of these was associated with a prominent “a” wave on the left ventricular pressure curve as illustrated in Figure 1. A similarly elevated LVedp was found in twentysix of fifty or approximately half of the control subjects. Nine of the fourteen patients had a cardiac index below 2.0 L. per minute per Ms. In the control group with coronary disease, the cardiac index was less than 2.0 L. per minute per M2. in only sixteen of fifty. In five of our patients a satisfaotory pulmonary capillary wedge pressure revealed a large 3” wave. Clinical Follow-Up. Four of our patients underwent mitral valve surgery, with survival and clinical improvement in two. Another patient (R.W.) had mitral valve replacement
combined with left ventricular aneurysmectomy, and one (W.A.) had mitral valvuloplasty combined with an anterior internal mammary artery implant. Both of these patients died in the early postoperative period. The condition of the remaining ten patients is relatively unchanged, except that three have had further myocardial infarcts.
* The distal right coronary artery supplied the inferior portion of the heart via the posterior descending artery in the interventricular groove [Ijr].
FIG. 1. Left %entricuIar and brachial artery pressure tracing of patient J.G. illustrating the elevated LVedp and prominent “a” ware.
COMMENTS
The clinical features of these patients are in general accord with those reported by others [l-8]. ECG
AMERICAN
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Papillary
Muscle
Dysfunction-..She~~,ilrnr
.jngina ib an almost invariable symptom. Thus in twenty cases of papillary muscle dysfunction described by Bashour [?] all but three In our series, twelve of patients had angina. fourt_eeIt patients had this symptom. It cannot IX stated whether this is due to the underlying coronary artery disease or to the left ventricular o\~~load imposed by the mitral regurgitation. I Iyprrtension was not a frequently associated fat tor; onlv two of our patients had an arterial diastolic pl’essure of 100 mm. Hg. .\lthough myocardial infarction is usually an antecedent to this condition, and the murmur m;~y first be detected following such an acute episode, [5,!41], four of our patients did not give a llistory of prior infarction and two of these for~l- h;id no electrocardiographic evidence of infarction at the time of study. Such a history i> not essential because postmortem studies have shown t.hat papillary fibrosis may occur with subendocardial infarction or without infarction at ali and yet produce mitral regurgitiltion [7,15-171. Transient murmurs attributed to papillary muscle dysfunction have been hc,;n-tl during episodes of angina and presumed m)ocardial &hernia [5]. ‘IX murmur had been present, when knowrl, for a period ranging from two months to ten years. This emphasizes the fact that mi~a1 regurgitation due to papillary muscle dysf‘llnction is compatible with long-term survival in contradistinction to actual separation of the papillary muscle from the mitral valve leaflet (papillary muscle of chordae tendineae rupture), in which death usually, although not always, supervenes within days or weeks [18]. All patients were in normal sinus rhythm, in (ontr.lst to mitral incompetence due to rheumatic. valvular heart disease in which atria1 fibrillation is common [19]. Possible explanations for the absence of atria1 fibrillation in this group of patients are (1) the left atria1 size is small, and (2) no process is analogous to the rheutnatic process which involves the left atrium as well as the valve. Whereas the presence of a fourth heart sound was reported to be an invariable finding in patients with flail mitral cusp by Cohen et al. [ZO], a third or fourth heart sound was present in only six of our patients (Fig. 2 and 3). The characteristics of the murmur have been studied and described by various investigators [I-3 81. Bashour described the murmur as holosystolic in all his twenty patients. Philips and Rurch, on the other hand, described a murmur VOI.
46.
,JUNE
1969
ECG II
‘(6”
rf ol.
,
I
FIG. 2. Phonocardiogram and apexcardiogram (AC(;) of patient A.T. demonstrating a prominent atria1 sound (S4) coincident with the large “a” waye on the ACG.
considered to be characteristic of papillary muscle dysfunction as late in systole, often with a diamond shape. Others [21] have reported the murmur as mimicking aortic stenosis, including radiation of the murmur to the neck. In five of our patients the murmur was holosystolic (Fig. 3). The remainder were either early, mid- or late systolic. An example of an early systolic murmur is shown in Figure 4. It is thus apparent that papillary muscle dysfunction does not produce a single characteristic murmur. The time of onset of the murmur was compared with time of onset of regurgitation studied by a fratne analysis of the cineventriculogram. The two coincided in each instance (Table 111) so that an early systolic murmur meant early regurgitation, etc.
FIG. 3. Phonocardiogram of patient J.M. There is a prominent sound in mid-diastole interpreted as a summation sound (S, and SS. The murmur, which extends throughout the whole of sl-srole, is diamontl-shaped.
868
Papillary
Muscle Dysfunction-S%elburne
et al.
ECG
PCG
ACG FIG. 4. Phonocardiogram and apexcardiogram of patient W.A. The murmur which starts with the first heart sound ceases before the second sound.
-1
RCA
m
--..
ksteromediai Pap#ary Muscle
FIG. 5. The schematic representation of the papillary muscle groups of the left ventricle with this blood supply in a right dominant coronary circulation. The insert from Estes et al. (Am. Heart J., 71: 356, 1966) [22] demonstrates the arrangement of the lesser order arteries supplying the papillary muscle in cascades.
dl
F
FIG. 6. The phonocardiogram of a patient in the control group illustrating the presence of a systolic murmur for which no explanation was found at the time of cardiac catheterization. AMERICAN
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Papillary
Muscle
Dysfunction-~~~~She/bllrne
Consideration of the mechanism of mitral val\re closure, and the part that the papillary muscles play in this, offers a possible explanation for the variation in time of occurrence of mitral regurgitation during systole. Although the exact mechanism of mitral valve closure is still not known, normal functioning of the papillary muscles is required. In the left ventricle tllere are usually two groups of papillary muscle,, the anterolateral and posteromedial. Chordae from each valve cusp are attached to each muscle group. The blood supply to these structures (Fig. 5) has been studied at postmorteln by special technics [22] and an orderly arrangement of two different sized arteries supplying the inner and outer portions of the muscles h;rs been demonstrated. In subjects with (oronary artery disease obvious deviations from the normal are found, often in association with scarring or infarction of the muscle [Z?]. Normal functioning of these muscles requires ll~althv myocardial fibers which shorten and a normal directional axis of pull upon shortening. Ei thel- of these may be affected in coronary at tery disease. Infarction with healing, i.e., fibrosis, may produce thinning and foreshortelling of the papillary muscle \vhich would result in mitral regurgitation of varying de
4 6,
JUNE
1969
P! a/.
800
nonfunctioning papillary muscle is adequate to keep the mitral valve closed during thrh Lovolumic phase of ventricular systole, but a5 llw ventricle gets smaller during ejection the ntitral valve is free to balloon up into the \3lve ring because the papillary muscle did not shorten adequately or at all to hold the cusp in place. However, one can visua1il.e the situation in which not only the papillary must le is danIaged but also its orientation is distorted so Lh;rt it renders the valve incompetent tlirougliout the whole of systole. Again, if the base ot rl~e papillary niuscle is an aneurysm which mo\‘es paradoxically during systole, the timing of t lie mitral incompetent murmur will coincide wit II the time of paradoxical expansion of 1tic aneurysm. These different types of papillar) muscle dysfunction may explain the differcsnt types of murmur observed. -4s is generally appreciated, systolic murmurs are sometimes found in patients with no good explanation for their presence. In our control grou I-’ seven of fifty patients had a systolic murmllr but no angiographically demonstrable mitral regurgitation. These murmurs were indistinguishable in timing, intensity, rharacter or radiation from those of our patient group (Fig. 6). It is interesting that all these seven patients had abnormal contrartion patterns on tile tine left ventriculograms but llle relation, if any, of asynergy to production of murmur cannot be stated at the present time. One can also postulate that they all had some aberration of mitral valve closure, permitting a degree of mitral reflux not detectable nngiographicallv. ElPctror/lrdiogram. There was no specific electrocardiographic finding in this ,group in contradistinction to other reports [h,24]. Onl! one of our patients showed J point depression in leads V, and V, as reported by Burch et al. [h]. Inferior or infero-lateral myocardial infai-ction was present in twelve of twenty patirnts reported by Bashour [?I. Anterior or lateral myocardial infarctions were seen in an additional four. In our group evidence of prior inyocartlial infarction was present in onlv Six patients, xvitli no consistent locus of infarction. Roentgcnographic Findings. Despite moderate to severe mitral incompetence the left atrium is not enlarged in patients with mitral insufficiency due to papillary muscle rupture. in contrast to patients with mitral insufficient\
870
Papillary
Muscle
Dysfunction-Shelburne
due to chronic rheumatic heart disease [25,26]. In our series the left atrium was enlarged in only four of fourteen patients. The murmur in these patients was known to have been present for ten, three, three and two years, respectively. This would support the previously offered suggestion that the left atria1 size may be related to the acuteness of the development of mitral insufficiency. Thus, in papillary muscle rupture when this is an acute event, the left atrium is small but in papillary muscle dysfunction in which the patient may survive for years, the left atrium enlarges as in rheumatic mitral incompetence. Hemodynamics. Although the left ventricular end diastolic pressure was elevated in approximately the same number of patients as control subjects, the cardiac index was clearly lower in our patient group (Table v). The effective cardiac output is probably compromised by the accumulation of many factors in addition to mitral insufficiency, i.e., severe three vessel coronary artery disease and left ventricular asynergy. Of note is the somewhat shorter systolic ejection period in our patient group as opposed to the control group, compatible with a lower resistance to ventricular emptying due to the mitral regurgitation. In three of our patients there was an apparent diastolic gradient across the mitral valve measured as a difference between the pulmonary wedge mean pressure and left ventricular diastolic mean. In each of these patients there was in the pulmonary a large “v” wave inscribed wedge and pulmonary artery pressure tracings. One of these patients (J.M.) was examined at autopsy and no evidence of mitral valve obstruction was found. Coronary Arteriography. As described by Gross [27] and Estes et al. [22,23], the anterolateral papillary muscle group is supplied via the left circumflex marginal artery and terminal branches of the left anterior descending artery (Fig. 5). The posteromedial muscle group may be supplied by these same arteries in a left dominant circulation but in the more common right dominance it is supplied by the distal branches of right coronary artery in the interventricular sulcus. Our patient group did not differ from the control
et al.
them the incidence of greater than 75 per cent stenosis of the right coronary artery was 60 per cent, of the left anterior descending artery 73 per cent and left circumflex artery 4T per cent. There was, however, a striking difference in the incidence of right coronary artery lesions in patients with papillary muscle dysfunction. Twelve of the fourteen (85 per cent) had stenoses greater than 75 per cent of the lumen and of the twelve right coronary artery lesions, six were complete occlusions. In Proudfit et al’s series [28] only seventy-seven of 293 right coronary artery lesions (26 per cent) were completely occluded. It would be interesting to know how often a complete occlusion of the right coronary artery is followed by the appearance of papillary muscle dysEunction. In our control group eight of fifty (16 per cent) had a complete occlusion of the right coronary artery and two of these had a systolic murmurof mitral insufficiency. Heikkila [5] found a high incidence of posterior papillary muscle involvement in an autopsy survey of patients who died with the murmur of mitral insufficiency. Because of its blood supply the posterior papillary muscle may be peculiarly susceptible to damage if the right coronary artery is suddenly compromised. The variations in the blood supply to the anterior papillary muscle may well protect it from profound ischemia and/or infarction. Ventriculography. It is tempting to extrapolate from a high incidence of right coronary artery lesions, and probable involvement of the posterior papillary muscle group, to mitral insufficiency of a specific type and radiation. In fact, left ventriculography in our patient group did not reveal anything unique about patients with right coronary lesions. A comparison of a motion analysis [II] of the ventriculo,grams of our patient group with ventriculo
JOURNAL
OF
MEDICINE
Papillary
Muscle
Dysfunction-
Our studies confirm this impression and emphasize that a frank, paradoxicallypulsating aneurysm is not necessary but rather sllbtle changes in ventricular contraction may be more common. As mentioned earlier, 93 per cent of our patients had either frank left ventricular aneurysms or less obvious forms of ventricular asynergy. The contribution of these abnormalities to the production of mitral insufficiency is clear: the role these abnormalities play in the total myocardial impairment-in and of themselves-should be emphasized. II’hen evaluating these patients for possible mitral valve sur$gery, one should be aware of theye considerations; indeed, surgery is probably only indicated when mitral regurgitation is severe and left ventricular contraction only rninimallv impaired. tl?-ilunc
tioll.
REFERENCFS
I BURGH, C;. E., DEPASQUALE, N. P. and PHILLIPS, J. H. 2.
3.
4.
5.
6.
7.
8.
9.
IO.
11.
Clinical manifestations of papillary muscle dysfunction. Arch. I&. Med., 112: 112, 1963. PHILLIPS, J. H., BURCH, G. E. and DEPASQUALE, N. P. The syndrome of papillary muscle dysfunction, its clinical recognition. Ann. Int. Med., 59: 508, 1963. BASIIOUR, F. A. Mitral regurgitation following myocardial infarction: the syndrome of papillary miteal regurgitation. Dis. Chest, 48: 113, 1965. BURNS, J. M. Papillary muscle dysfunction: a cause of mitral incompetence. Minnesota Med., 48: 1458, 1965. HEIKKIL4, 1. Mitral incompetence complicating acute myocardial infarction. &it. Heart J., 29: lfi’, 1!)67. BURCH, G. E., DEPASQUALE, N. P. and PHILLIPS, J. H. 7 he syndrome of papillary muscle dysfunction. Am. Heart J., 75: 399, 1968. Lorry, I... ZUCKER, I. R. and BERNSTEIN, A. Clinical and pathological observations in acute papillary muscle infarction (report of five cases). Vast. Dk., 3: 168. 1966. ORLANDO, M. D., WOOLEY, C. F., SCORPELLI, D. and RYAN, J. M. Mitral valve regurgitation caused by infarcted muscles: a report of fifteen cases. (Abstract.) Ann. ht. Med., 61: 801, 1964. SONES, F. M., JR. and QHIREY, E. K. Cinecoronary arteriographv. Mod. Concepts Cordiorjasc. Dis., 31: 7:15, 1962. Kehrp, H. G., E\ANS, H., ELLIOTT, W. C. and GORLIN, R. Diagnostic accuracy of selective coronary cinearteriography. Circulation, 36: 526, 1967. KI.TIN, M. D., HERMAN, M. V. and GORLIN, R. A hemodynamic studv of left ventricular aneurysm. C’irctclntion, 35: 614, 1967.
VOL.
46,
JUNE
1969
-. .S/te/hurnt~ rf N/.
12. SOKOLO~, M. and LYON, ‘1‘. I’. The venlriculal (onplex in left ventricular hypcrtrophy as obtained by unipolar precordial and limb leads. ,1 !?l. Hecr,-t J., .37: 161, 1949. 13. JAMES, T. The Anatomy of the Coronarv Ar~(.ries. A’trw York, 1961. Paul B. Hoeber, Inc. 14. GOKLLN, 1~. Pain in the chest of sudden onset ~s\otinted with a cardiac murmur. MPT(~Englnnd 1. Med., 275: 1244, 1966. 15. DEPASQUz\LE, N. P. and BURCH, G. E. The necropsy incidence of gross scars and acute infarction of the papillary muscles of the left ventricle. rlln I. Casdiol., 17: 169, 1966. 16. HIRER, C. F., TAYLOR, D. E. M. and WADE, J. I). The effect of papillary muscle damage on atrioventricular valve function in the left heart. Jjunrt. 1. &per. Physiol., 50: 15, 1965. 17. TAYLOR, D. E. M., WADE, J. M. and HIDER, C. 1;. Heart valve lesions following papillarv nruucle damage. Nature, 207: 530, 1965. 18. HELLER, J. A., JR. and MORROW, A. G. Experimental mitral insufficiency. Szhrgery, 38: 518, 1955. 19. WOOD, P. Disease of the Heart and Circulation. I’_ 514. London, 1961. Eyre & Spottiswood. 20. COHEN, L. S., MASON, D. T. and BRAUNWALD, E Signilicance of an atria1 gallop sound in mitral regurgitation: a clue to the diagnosis of rupturc%tl chordae tendineae. Circulation, 35: 112,1967. 21. MERCER, E. N. and WALTERS, M. B. Mitral regurgitation simulating aortic stenosis. Cnnada :!4. .,I. 1.. 93: 413, 1965. 22. ESTES, E. H., DALTON, F. M., ENTMAN, M. C., DIXON, H. B. and HACKEL, D. B. The anatomy and blood supply of the papillary muscles of the left yentricle. .4m. Heart J., 71: 356, 1966. 23. ESTES, E. I-l., ENTMAN, M. L., DIXON, H. I%. ;md HACKEI., D. B. The vascular supply of the left ventricular wall. Ant. Heal-t I.. 71: 58, 1966. 24. PHILLIPS, J. H., DEPASQUALE, N. P. and BURGH, G. E. The elcctrocardiogTam in infarction of the anterolateral papillary muscle. AT)!. Heor/. 1.. 66: :138. 1963. 25. ROISFRTS, IV. C., BRAUNWALD, E. and MORROW. ,\. (;. Acute severe mitral regurgitation secondary to ruptured chordae tendineae: clinical hemodvnamic and pathologic considerations. Ci,-ccllntion. 33: 58, 1966. 26. SANDERS, C. A., AUSTEN, W. G., HARTI~ORNE, J, IV., DINshIoRE, R. E. and SCANNELL, J, G. Diagnosis and surgical treatment of mitral regurgitation secondary to ruptured chordae tendinrar. New England J. Med., 276: 943, 1967. 27. GROSS, L. The Blood Supply to the Heart in its Anatomical and Clinical Aspects. New \‘ork, 1!121. Paul B. Hoeber, Inc. 28. PROCDFIT, W. L.. CAIRLEY, E. K. and SONES, F. M., JR. Distribution of arterial lesions demonstrn ret1 by cinecoronary arteriogaphv. Circu/ation. 36: 54. 1967.
of Papillary
Dysfunction*
Correla tiue Clinical and Angiographic JAMES C. SHELBURNE,
M.D.,?
DOROTHY
RUBINSTEIN,
M.D.
Stu&
and RICHARD
GORLIN,
M.D.
Boston, Massachusetts Fourteen patients with mitral insufficiency due to papillary muscle dysfunction and fifty control subjects with coronary atherosclerosis but no mitral insufficiency were evaluated clinically and studied by right and left heart catheterization, selective coronary arteriography and left ventricular cineangiography. The murmur of this condition was found to vary in timing from early to late systole or to be holosystolic; the site, radiation and intensity of the murmur were inconstant. These features bore no relation to the degree of angiographically visualized mitral insufficiency, but there was precise correlation between timing of onset of regurgitation by ventriculography and timing of the murmur within systole. Seven of the control subjects who had murmurs clinically indistinguishable from the patient group did not have angiographically demonstrable mitral regurgitation. No characteristic electrocardiographic pattern was found nor could specific papillary muscle group involvement be distinguished angiographically. All patients had three vessel coronary artery disease, but with an increased incidence of severe right coronary artery lesions. Abnormal left ventricular systolic contraction was found in all but one of the patient group. The hemodynamic abnormalities such as markedly reduced cardiac output may be as much due to the left ventricular asynergy as to the mitral incompetence. This factor deserves full consideration if corrective surgery of the valvular lesion is contemplated.
A
correlate with the presence and severity of the mitral insufficiency? (3) What is the pathophysiology of the lesion? (4) What are the associated coronary artery lesions? (5) What is the prognosis of this condition?
LTHOUGH the acute and chronic syndromes of papillary muscle dysfunction have been described before [I-83, there is no report in which the coronary arterial anatomy and the nature of the valvular incompetence have been studied during life by angiographic technics. In this study the clinical, hemodynamic and angiographic findings were analyzed in fourteen patients with mitral insufficiency due to
MATERIAL The fourteen patients here described were seen in our laboratory during the past three years (19651968) because of either angina pectoris or congestive heart failure. The criteria for inclusion in the study were as foIlows: (1) The existence of a systolic murmur and demonstration of mitral insufficiency by angiography. (2) The absence of (a) all stigmata of rheumatic heart disease, (b) congenital
papillary muscle dysfunction. The study was undertaken with the following questions in mind: (1) Are there any characteristic clinical features which allow this diagnosis to be made? (2) How do the characteristics of the murmur
* From the Cardiovascular Unit, Department of Medicine, Peter Bent Brigham Hospital and Harvard Medical School. This study was supported by U. S. Public Health Service Grants 5RO1-HE08591-04, TTOl-HE05679-03, lPOl-HEI 1306-01 and the Kriendler Memorial Foundation. Requests for reprints should be addressed to Richard Gorlin, M.D., Cardiovascular Unit, Peter Bent Brigham Hospital, 721 Huntington Avenue, Boston, Massachusetts 02115. Manuscript received June 17, 1968. t Postdoctoral Trainee, National Heart Institute, U. S. Public Health Service. Present address: Department of Medicine, University of California School of Medicine, The Center for the Health Sciences, I-OS .4ngeles, California 90024.
862
AMERICAN
JOURNAL
OF
MEDICINE
Muscle
Papillary
lIysfunc%iorlTABLE
C.L,NIC:AL
I 2
J.G W.(1.
.i;. ;3,
!bl \I
3 4
L.hl. A.7
52, \I
I’rrarni l’rrsmt 5 VT. Non.?
FEATURES
Norm.11 52 hid
110!70
lf
Normal
Normal
N0n.Z NOW
11 o/70 120/90
Not remarkable Bitid. 4f
Soft Normal
N0rm.Xl Fixed sphl
s1; s, Sr
11.x.
42, F
MR. A.S.
-59, \I ;4. hf
11
R.!V.
4‘,
12
.I.\I.
lJ8.11
13
Y.1 ;.
73, F
14
N \I.
bi. F
2 \7. 3 yr.
NOW
140/90 125/80
Diff
18O,e30 140 ‘90
Not rcmwk., hlr
1+
1 yr.
?
NOX
120,‘70
1+
Normal
Norm.il
None x \r.
2 mo. ?
1 yr. None
lGO/lOO 115/70
Not rcmd.rk,ible Bifid impulsr
Normal Normal
Nnne
2 yr.
2 ?P.
130,‘lOO
3+
Soft
Normal F’aradoxical split with angina attack Reversed split
Ii yr. ’ 2 yr. 6 yr.
2 yr.
7 yr.
120/70
Not remarkable
Normal
Normal
?
None
130,/80
Bilid
N0IIllal
NO~lTl‘Il
5 )r. 2 yr.
3 yr.
None
120/‘70
Nor remarkable
Normal
Normal
Sa, ,5r s:
s,
SI Intermilrenc
SI
mfarcr.
heart disease, (c) bacterial endocarditis, (d) history of chest trauma, (e) idiopathic hypertrophic subaortic stenosis. The diagnosis was confirmed at either operation or necropsy in five patients. The subjects in the series ha\e been followed for six to thirty-two months at the time of writing. Fifty patients studied in similar fashion during the same time period served as controls. Each was shown to have coronarv atherosclerosis but no mitral insufficiency by yen&culography. METHODS
All patients were admitted to the hospital, were seen by one or more of us and underwent left and right heart catheterization. The evaluation of each patient included chest roentgenogram (four views with barium swallow)). electrocardiogram and phonocardiogram. Alurmurs were graded in intensity from 1 to 6. Pressures were inscribed on a Sanborn No. 560 polybeam photographic recorder using a Statham P23D transducer. Cardiac outputs were measured by means of indocyanine green dye and a Gilford densitometer. Selective cineangiography of the coronary arteries was performed in multiple projections by the Soncs technic [9]. IIford Pan F 16 mm. film was used and the angiograms were registered by means of either a 6 inch or a dual-field General Electric image amplifier. The studies were reviewed by at least two of us independently and all films were of high diagnostic quality [lOI. Disease in a coronary arteq was consideied significant when stenosis was greater than 75 per cent of the lumen JCXE
Normal Loud
ixone
9 10
46,
Fixed split Pz loud
6 mo. 3 yr.
R
VOL.
Soft LOWi
?
;v. hl 35. hi
myocardial
2 +
10 yr. ?
A.K.
* Diaptnlgmatic
DYSFUNCTION
N0ll.Z
G.1.. w 1.
Prwnr II \r. Prrwit I, ,r.
MCSCLE
Present ? duration 1 yr. NOW
.5
Pn sent 5 \r. NO”?
PAPILLARY
5 yr. 3 yr.
6 7
\I
I
WITH
10 yr.* 5 yr.
<,I,51 l’rrsmt 14 yr. c \r. 3 yr. 2 7. 5’).51 Pmcnt None 4 w. Prrscn1 Prcsenr 3 yr. Prcsrni 7 \r. K
OF PATIENTS
x0 ?
.YMi~.tr-r/c’rt 01.
1969
diameter. Ventriculography was performed at rest in all patients, with power injections of 40 to 60 ml. of 75 per cent Hypaque@ into the left ventricle via a No. 7 or No. 8 Lehman catheter. Film speed was 60 frames per second and one or two projections were used, including the right anterior oblique. Each ventriculogram was interpreted qualitatively for uniformity of contraction at all points along the inner ventricular surface, as well as for the ventriclelar chamber size, shape and wall thickness [Ill. Only normally conducted beats were selected for study. A qualitative estimate of the severity and time of occurrence of mitral regurgitation was made in each case. RESULTS
The clinical features of the patients are summarized in Tables I, II and III. Eleven of the fourteen patients were male, Clinical
Features.
their ages ranged from thirty-three to sixtyeight years. All but two of our patients gave a history of angina which had been present for up to ten years. Five of the fourteen patients had clinically overt heart failure. Ten gave a definite history of prior myocardial infarction. The murmur had been present, when known, for a period rarqing from two months to ten years. In several patients the murmur was first heard following an acute myocardial infarction.
864
Papillary
Muscle Dysfunction-Shelburne
et al.
TABLE II ELECTROCARDIOGRAPHIC FEATURESOF PATIENTSWITH PAPILLARY MUSCLEDYSFUNCI’ION
ChSe No. Patient
Left Ventricular HyperRhythm
Axis
trophy
Left Atrial EnIargement
NAD
Present
Present
RAD NAD
Present Present
Present
1
J.G.
2 3
W.G. L.M.
NSR PR = 0.22 sec. NSR NSR
4
A.T.
NSR
NAD
5
A.E.
NSR
LAD
6
G.L.
NAD
7 8 9 10 11
W.A. H.K. M.R. A.S. R.W.
LAD NAD LAD NAD NAD
12
J.M.
NSR VPB’s NSR NSR NSR NSR NSR PR = 0.23 sec. NSR
13
F.G.
NSR
LAD
14
N.M.
NSR
LAD
ST-T Abnormalities
Myocardial Infarct*
Conduction Defcctt IVCD
T 1 II,’ ;;I, AVF .I depression in vz-v, T flat I, AVL, V6_V6 T flat throughout tracing ST-T _1I, II, AVL, V4-V,
Present
. Present
IVCD ST 4 I, ;I,’ Vg-VB I&B T -1 II, ;;I.,
AVF
.
NAD
, .
T&I,AVLSTt with V2-V, T _1II, II-I, AVF, Vs-Vs
Old%MI Old .1MI Possible old DMI Old AM1
IVCD
Possible old ASMI
NOTE: NSR = normal sinus rhythm. NAD = normal axis deviation, i.e., $30” to +90”; L:\D = left axis deviation, i.e., +30” to -30“; RAD = right axis deviation, i.e., >+90”. * AM1 = anterior myocardial infarct; DMI = diaphragmatic myocardial infarct; ASMI = anteroseptal myocardial infarct. t IVCD = intraventricular conduction defect; RBBB = right bundle branch block.
The apical impulse was left ventricular in character in nine of fourteen patients and frequently it was diffuse or bifid suggesting ventricular aneurysm. A third or fourth heart sound was heard in six of fourteen patients. Only two patients had a palpable systolic thrill. The systolic murmur was of moderate (grade 3 to 4) intensity in eight patients and grade 2 in the remaining six. In five patients the murmur was holosystolic; in two, late systolic; in seven, either early or mid-systolic in timing. The murmur was usually heard at the apex and lower left sternal border and it radiated to the axilla. In no patient was the murmur heard in the neck. Electrocardiography. The electrocardiographic changes are outlined in Table II. All patients were in normal sinus rhythm. No specific electrocardiographic pattern was seen in this group. Evidence of prior myocardial infarction was noted in six, left ventricular hy-
pertrophy [f2] in five and nonspecific Sl‘-T abnormalities in eight. Roentgenography. The heart was enlarged due to enlargement of the left ventricle in eight patients. The right ventricle was prominent in three. The left atrium was enlarged in only four. The lung fields were unremarkable in all patients. Reflux of dye into the Ventriculography. left atrium from the left ventricle occurred in all patients. In Table III the timing of the murmur during systole is compared with the time of appearance of dye into the left atrium. Although there was no correlation with the radiation or character of the murmur, there was excellent agreement between the appearance time of mitral regurgitation and the clinical timing of the murmurs. There was no uniform correlation between the amount of regurgitation and the intensitv of the murmur. Paradoxical systolic expansion of the opacified left
Muscle Dysfunction-m -,Shrltwnr
Papillary
Lelt I’dtKUI
\‘e”tric~d.rr Motion*
.I.(:.
‘>OTO npiwl
1V.c:
Marked
L.hl.
Diffusr
.~“r,q
Regirgitatio”
~“3
3+,
hypohinesis hypokincsis
4f
.?.I
3f
%.R.
Norm.,1
G.L.
Large
W.A.
Akinesis, ;~“terolateral wall Large apical aneurysm Generalized hypokinesis
1i.K. M.R. A.S.
J.M. F.G. N.M.
Apical aneurysm Apical paradox hypokinesis
=
generalized
with systole systolic
Grade
4
Grade
1
Soft
elirly
Grade
4
Deacend~
Grade
3
severe, systolic moderate,
latesystolic
I to
3 to 4+,
early
Grade
2
Grade
2
Soft
Grade
3
Soft
Grade Grade
2 3
Soft
Grade
2
Grade
4
Ejection
syst0le 2+,
early systole
Grade
4
1 f,
early systole
Grade Grade
2 2
3+, early systolic
inferior
reduction
e.ml)
E.wly
Intensity
3+, mid to late systole 1 to 2+, early to mid systole 3+, “ondiagnostic I+, early systole 2+, early systale I+, early systole
aneurysm
Inferior and apical aneurysm and akinesis Aneurysm, anteroapical B of left ventricle Generalized hypokinesis
R.W.
* l-fypokinesia
contraction apical
early,
onsetof
3+,
in normal
holo-
degree
of contraction;
Soft
nkinesis
TABLE RESULTS
OF CORONARY
ARTERIOGRAPNY
Coronary Patient
Dominance
J.G. W.G. L.M. A.T. A.R.
R R L R R
G.L.
R
W.A.
R
l3.K.
R
M.R.
R
A.S.
I.
* L.41)
=
90 y0 stenosis Proximal 50% stenosis Proximal 90 7: stenosis 90% stenosis 75 y0 stenosis of 1st diagonal branch 75 “ib stenosis of main LCA Narrow 1st diagonal branch 75% stenosis distal to 1st diagonal branch Intramural disease; 100% stenosis of 1st diagonal branch Proximal 100%
R
Proximal
J.M.
R
LCA
1; G.
R
Proximal loo%;, 1st diagonal branch 755 xc“osia 75 cc stenosis
iefr anterior
R
descending:
Artery*
75 y0 stenosis
100%
I.(:F
=
left circomHex:
=
local
absence
of wall
motion.
IV
1N PATIENTS
LAD
R.W.
A.M.
et al.
Lesions
WITH
PAPILLARY
MUSCLE
DYSFUNCI‘ION
C:l&iter&
(Stenosis)
LCF
Proximal 50 Y0 stenosis Proximal 90% stenosis Intramural disease Intramural disease 30y0 stenosis of marginal branch Proximal 907‘ stenosis
Proximal 100%
90%
None Nonr None Non,.
strnosis
,.
NOX”d
95 70 stenosis Mid 1007,
Right
90 yc stenosis
Lefr
LCA calcium nondiagnostic Marginal 90% stenosis
Intramural disease, distal 50% stenosis Proximal 75’“, stenosis
Leh
75y0 stenosis, 1st mxginal circumflex
ProYimnl
8OZ
lOO?E of posterior descending 50% stenosis of 1st marginal circumflex 50 y0 stewxs
Proslmal
loo”;
Mid
90 $
stenosis
Proximal
TU
From
RCA
Proxim.d
RCA
=
nsh~
coromw
100”;
;
Proximal 75 ‘;i, mid 100% marginal 9Opb stenosis Normdl
Proximal
;wterx
loo’:
Smt
stenosib
Left Richt L& Ixtr Riqht
Right Left Right Let-c Right .eft
I
Right Lefr
Left
Right Left
Left Right
I.eT1
866
Papillary
Muscle
et al.
Dysfunction-Shelburne
TABLE v HEMoDYNAMIcsOF PATIENTSWITH PAPILLARY MUSCLE Case NO. __-_ 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Patient J.G. \Y.G. L.M. A.T. AK. G.L. \Y.!\. H.K. M.R. N.S. R.\V. J.M. F.G. N.M.
PA s/d
RV s/d
R.4,
PC,
5;;; 53/2 30/8
1 1 2 5
‘Zj
4;;;9 55/21 25/11 78/34 60/30
7j;13 60/3
‘S 6
‘%
3%
‘.’4
23 10
‘i,
LV s/d 106/25 136/6 99/10 107/12 138,‘20 175/54 127/36 110/12 184/12 120/3 115/12 97/26
72/34 8
133/20 124/15
DYSFUNCTION
sep/SEP
SER
CI
SI
BA s/d
0.24/23 0.25/19 0.24/20 0.32/19 0.32/19 0.30/22 0.22/26 0.28/24 0.30/23 0.40/19 0.20/18 0.22122 0.28/25 0.28/24
79 92 85 97 144 58 68 100 110 74 45 64 153 68
1.8 1.7 2.1 1.8 2.7 1.3 1.6 2.6 32 1.4 .79 1.4 2.4 1.4
19 23 22 31 46 17 14 28 41 29 9 14 25 16
105/72 167/73 103/57 1 lo/64 133/71 174/88 120/90 122/70 190/83 133/72 87/67 119/65 136/80 123/75
NOTE: Pressures are recorded in mm. Hg. PA = pulmonary artery; RV mean; PCm = pulmonary capillary wedge mean; LV = left ventricle; sep beat); SEP = systolic ejection period (seconds per beat per minute). SER = per systolic second per meter squared). CI = cardiac index (L. per minute (cc.per minute per meter squared). B.4 = bra&al artery.
= right ventricle; RAm = right atria1 = systolic ejection period (seconds per systolic ejection rate (cubic centimeters per meter squared). SI = stroke index
atria1 chamber was noted in five of the fourteen patients. Coronary Arteriogra@y. Twelve of the fourteen patients in the study group had right dominant coronary circulation.* The incidence of severe stenosis of each of the coronary arteries is shown in Table IV. The right coronary artery was affected in twelve of fourteen patients, the left anterior descending in ten and the left circumflex in seven. Hemodynamics (Table V). Seven of our fourteen patients had left ventricular enddiastolic pressure (LVedp) greater than 12 mm. Hg; each of these was associated with a prominent “a” wave on the left ventricular pressure curve as illustrated in Figure 1. A similarly elevated LVedp was found in twentysix of fifty or approximately half of the control subjects. Nine of the fourteen patients had a cardiac index below 2.0 L. per minute per Ms. In the control group with coronary disease, the cardiac index was less than 2.0 L. per minute per M2. in only sixteen of fifty. In five of our patients a satisfaotory pulmonary capillary wedge pressure revealed a large 3” wave. Clinical Follow-Up. Four of our patients underwent mitral valve surgery, with survival and clinical improvement in two. Another patient (R.W.) had mitral valve replacement
combined with left ventricular aneurysmectomy, and one (W.A.) had mitral valvuloplasty combined with an anterior internal mammary artery implant. Both of these patients died in the early postoperative period. The condition of the remaining ten patients is relatively unchanged, except that three have had further myocardial infarcts.
* The distal right coronary artery supplied the inferior portion of the heart via the posterior descending artery in the interventricular groove [Ijr].
FIG. 1. Left %entricuIar and brachial artery pressure tracing of patient J.G. illustrating the elevated LVedp and prominent “a” ware.
COMMENTS
The clinical features of these patients are in general accord with those reported by others [l-8]. ECG
AMERICAN
JOURNAL
OF
MEDICINE
Papillary
Muscle
Dysfunction-..She~~,ilrnr
.jngina ib an almost invariable symptom. Thus in twenty cases of papillary muscle dysfunction described by Bashour [?] all but three In our series, twelve of patients had angina. fourt_eeIt patients had this symptom. It cannot IX stated whether this is due to the underlying coronary artery disease or to the left ventricular o\~~load imposed by the mitral regurgitation. I Iyprrtension was not a frequently associated fat tor; onlv two of our patients had an arterial diastolic pl’essure of 100 mm. Hg. .\lthough myocardial infarction is usually an antecedent to this condition, and the murmur m;~y first be detected following such an acute episode, [5,!41], four of our patients did not give a llistory of prior infarction and two of these for~l- h;id no electrocardiographic evidence of infarction at the time of study. Such a history i> not essential because postmortem studies have shown t.hat papillary fibrosis may occur with subendocardial infarction or without infarction at ali and yet produce mitral regurgitiltion [7,15-171. Transient murmurs attributed to papillary muscle dysfunction have been hc,;n-tl during episodes of angina and presumed m)ocardial &hernia [5]. ‘IX murmur had been present, when knowrl, for a period ranging from two months to ten years. This emphasizes the fact that mi~a1 regurgitation due to papillary muscle dysf‘llnction is compatible with long-term survival in contradistinction to actual separation of the papillary muscle from the mitral valve leaflet (papillary muscle of chordae tendineae rupture), in which death usually, although not always, supervenes within days or weeks [18]. All patients were in normal sinus rhythm, in (ontr.lst to mitral incompetence due to rheumatic. valvular heart disease in which atria1 fibrillation is common [19]. Possible explanations for the absence of atria1 fibrillation in this group of patients are (1) the left atria1 size is small, and (2) no process is analogous to the rheutnatic process which involves the left atrium as well as the valve. Whereas the presence of a fourth heart sound was reported to be an invariable finding in patients with flail mitral cusp by Cohen et al. [ZO], a third or fourth heart sound was present in only six of our patients (Fig. 2 and 3). The characteristics of the murmur have been studied and described by various investigators [I-3 81. Bashour described the murmur as holosystolic in all his twenty patients. Philips and Rurch, on the other hand, described a murmur VOI.
46.
,JUNE
1969
ECG II
‘(6”
rf ol.
,
I
FIG. 2. Phonocardiogram and apexcardiogram (AC(;) of patient A.T. demonstrating a prominent atria1 sound (S4) coincident with the large “a” waye on the ACG.
considered to be characteristic of papillary muscle dysfunction as late in systole, often with a diamond shape. Others [21] have reported the murmur as mimicking aortic stenosis, including radiation of the murmur to the neck. In five of our patients the murmur was holosystolic (Fig. 3). The remainder were either early, mid- or late systolic. An example of an early systolic murmur is shown in Figure 4. It is thus apparent that papillary muscle dysfunction does not produce a single characteristic murmur. The time of onset of the murmur was compared with time of onset of regurgitation studied by a fratne analysis of the cineventriculogram. The two coincided in each instance (Table 111) so that an early systolic murmur meant early regurgitation, etc.
FIG. 3. Phonocardiogram of patient J.M. There is a prominent sound in mid-diastole interpreted as a summation sound (S, and SS. The murmur, which extends throughout the whole of sl-srole, is diamontl-shaped.
868
Papillary
Muscle Dysfunction-S%elburne
et al.
ECG
PCG
ACG FIG. 4. Phonocardiogram and apexcardiogram of patient W.A. The murmur which starts with the first heart sound ceases before the second sound.
-1
RCA
m
--..
ksteromediai Pap#ary Muscle
FIG. 5. The schematic representation of the papillary muscle groups of the left ventricle with this blood supply in a right dominant coronary circulation. The insert from Estes et al. (Am. Heart J., 71: 356, 1966) [22] demonstrates the arrangement of the lesser order arteries supplying the papillary muscle in cascades.
dl
F
FIG. 6. The phonocardiogram of a patient in the control group illustrating the presence of a systolic murmur for which no explanation was found at the time of cardiac catheterization. AMERICAN
JOURNAL
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Papillary
Muscle
Dysfunction-~~~~She/bllrne
Consideration of the mechanism of mitral val\re closure, and the part that the papillary muscles play in this, offers a possible explanation for the variation in time of occurrence of mitral regurgitation during systole. Although the exact mechanism of mitral valve closure is still not known, normal functioning of the papillary muscles is required. In the left ventricle tllere are usually two groups of papillary muscle,, the anterolateral and posteromedial. Chordae from each valve cusp are attached to each muscle group. The blood supply to these structures (Fig. 5) has been studied at postmorteln by special technics [22] and an orderly arrangement of two different sized arteries supplying the inner and outer portions of the muscles h;rs been demonstrated. In subjects with (oronary artery disease obvious deviations from the normal are found, often in association with scarring or infarction of the muscle [Z?]. Normal functioning of these muscles requires ll~althv myocardial fibers which shorten and a normal directional axis of pull upon shortening. Ei thel- of these may be affected in coronary at tery disease. Infarction with healing, i.e., fibrosis, may produce thinning and foreshortelling of the papillary muscle \vhich would result in mitral regurgitation of varying de
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nonfunctioning papillary muscle is adequate to keep the mitral valve closed during thrh Lovolumic phase of ventricular systole, but a5 llw ventricle gets smaller during ejection the ntitral valve is free to balloon up into the \3lve ring because the papillary muscle did not shorten adequately or at all to hold the cusp in place. However, one can visua1il.e the situation in which not only the papillary must le is danIaged but also its orientation is distorted so Lh;rt it renders the valve incompetent tlirougliout the whole of systole. Again, if the base ot rl~e papillary niuscle is an aneurysm which mo\‘es paradoxically during systole, the timing of t lie mitral incompetent murmur will coincide wit II the time of paradoxical expansion of 1tic aneurysm. These different types of papillar) muscle dysfunction may explain the differcsnt types of murmur observed. -4s is generally appreciated, systolic murmurs are sometimes found in patients with no good explanation for their presence. In our control grou I-’ seven of fifty patients had a systolic murmllr but no angiographically demonstrable mitral regurgitation. These murmurs were indistinguishable in timing, intensity, rharacter or radiation from those of our patient group (Fig. 6). It is interesting that all these seven patients had abnormal contrartion patterns on tile tine left ventriculograms but llle relation, if any, of asynergy to production of murmur cannot be stated at the present time. One can also postulate that they all had some aberration of mitral valve closure, permitting a degree of mitral reflux not detectable nngiographicallv. ElPctror/lrdiogram. There was no specific electrocardiographic finding in this ,group in contradistinction to other reports [h,24]. Onl! one of our patients showed J point depression in leads V, and V, as reported by Burch et al. [h]. Inferior or infero-lateral myocardial infai-ction was present in twelve of twenty patirnts reported by Bashour [?I. Anterior or lateral myocardial infarctions were seen in an additional four. In our group evidence of prior inyocartlial infarction was present in onlv Six patients, xvitli no consistent locus of infarction. Roentgcnographic Findings. Despite moderate to severe mitral incompetence the left atrium is not enlarged in patients with mitral insufficiency due to papillary muscle rupture. in contrast to patients with mitral insufficient\
870
Papillary
Muscle
Dysfunction-Shelburne
due to chronic rheumatic heart disease [25,26]. In our series the left atrium was enlarged in only four of fourteen patients. The murmur in these patients was known to have been present for ten, three, three and two years, respectively. This would support the previously offered suggestion that the left atria1 size may be related to the acuteness of the development of mitral insufficiency. Thus, in papillary muscle rupture when this is an acute event, the left atrium is small but in papillary muscle dysfunction in which the patient may survive for years, the left atrium enlarges as in rheumatic mitral incompetence. Hemodynamics. Although the left ventricular end diastolic pressure was elevated in approximately the same number of patients as control subjects, the cardiac index was clearly lower in our patient group (Table v). The effective cardiac output is probably compromised by the accumulation of many factors in addition to mitral insufficiency, i.e., severe three vessel coronary artery disease and left ventricular asynergy. Of note is the somewhat shorter systolic ejection period in our patient group as opposed to the control group, compatible with a lower resistance to ventricular emptying due to the mitral regurgitation. In three of our patients there was an apparent diastolic gradient across the mitral valve measured as a difference between the pulmonary wedge mean pressure and left ventricular diastolic mean. In each of these patients there was in the pulmonary a large “v” wave inscribed wedge and pulmonary artery pressure tracings. One of these patients (J.M.) was examined at autopsy and no evidence of mitral valve obstruction was found. Coronary Arteriography. As described by Gross [27] and Estes et al. [22,23], the anterolateral papillary muscle group is supplied via the left circumflex marginal artery and terminal branches of the left anterior descending artery (Fig. 5). The posteromedial muscle group may be supplied by these same arteries in a left dominant circulation but in the more common right dominance it is supplied by the distal branches of right coronary artery in the interventricular sulcus. Our patient group did not differ from the control
et al.
them the incidence of greater than 75 per cent stenosis of the right coronary artery was 60 per cent, of the left anterior descending artery 73 per cent and left circumflex artery 4T per cent. There was, however, a striking difference in the incidence of right coronary artery lesions in patients with papillary muscle dysfunction. Twelve of the fourteen (85 per cent) had stenoses greater than 75 per cent of the lumen and of the twelve right coronary artery lesions, six were complete occlusions. In Proudfit et al’s series [28] only seventy-seven of 293 right coronary artery lesions (26 per cent) were completely occluded. It would be interesting to know how often a complete occlusion of the right coronary artery is followed by the appearance of papillary muscle dysEunction. In our control group eight of fifty (16 per cent) had a complete occlusion of the right coronary artery and two of these had a systolic murmurof mitral insufficiency. Heikkila [5] found a high incidence of posterior papillary muscle involvement in an autopsy survey of patients who died with the murmur of mitral insufficiency. Because of its blood supply the posterior papillary muscle may be peculiarly susceptible to damage if the right coronary artery is suddenly compromised. The variations in the blood supply to the anterior papillary muscle may well protect it from profound ischemia and/or infarction. Ventriculography. It is tempting to extrapolate from a high incidence of right coronary artery lesions, and probable involvement of the posterior papillary muscle group, to mitral insufficiency of a specific type and radiation. In fact, left ventriculography in our patient group did not reveal anything unique about patients with right coronary lesions. A comparison of a motion analysis [II] of the ventriculo,grams of our patient group with ventriculo
JOURNAL
OF
MEDICINE
Papillary
Muscle
Dysfunction-
Our studies confirm this impression and emphasize that a frank, paradoxicallypulsating aneurysm is not necessary but rather sllbtle changes in ventricular contraction may be more common. As mentioned earlier, 93 per cent of our patients had either frank left ventricular aneurysms or less obvious forms of ventricular asynergy. The contribution of these abnormalities to the production of mitral insufficiency is clear: the role these abnormalities play in the total myocardial impairment-in and of themselves-should be emphasized. II’hen evaluating these patients for possible mitral valve sur$gery, one should be aware of theye considerations; indeed, surgery is probably only indicated when mitral regurgitation is severe and left ventricular contraction only rninimallv impaired. tl?-ilunc
tioll.
REFERENCFS
I BURGH, C;. E., DEPASQUALE, N. P. and PHILLIPS, J. H. 2.
3.
4.
5.
6.
7.
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IO.
11.
Clinical manifestations of papillary muscle dysfunction. Arch. I&. Med., 112: 112, 1963. PHILLIPS, J. H., BURCH, G. E. and DEPASQUALE, N. P. The syndrome of papillary muscle dysfunction, its clinical recognition. Ann. Int. Med., 59: 508, 1963. BASIIOUR, F. A. Mitral regurgitation following myocardial infarction: the syndrome of papillary miteal regurgitation. Dis. Chest, 48: 113, 1965. BURNS, J. M. Papillary muscle dysfunction: a cause of mitral incompetence. Minnesota Med., 48: 1458, 1965. HEIKKIL4, 1. Mitral incompetence complicating acute myocardial infarction. &it. Heart J., 29: lfi’, 1!)67. BURCH, G. E., DEPASQUALE, N. P. and PHILLIPS, J. H. 7 he syndrome of papillary muscle dysfunction. Am. Heart J., 75: 399, 1968. Lorry, I... ZUCKER, I. R. and BERNSTEIN, A. Clinical and pathological observations in acute papillary muscle infarction (report of five cases). Vast. Dk., 3: 168. 1966. ORLANDO, M. D., WOOLEY, C. F., SCORPELLI, D. and RYAN, J. M. Mitral valve regurgitation caused by infarcted muscles: a report of fifteen cases. (Abstract.) Ann. ht. Med., 61: 801, 1964. SONES, F. M., JR. and QHIREY, E. K. Cinecoronary arteriographv. Mod. Concepts Cordiorjasc. Dis., 31: 7:15, 1962. Kehrp, H. G., E\ANS, H., ELLIOTT, W. C. and GORLIN, R. Diagnostic accuracy of selective coronary cinearteriography. Circulation, 36: 526, 1967. KI.TIN, M. D., HERMAN, M. V. and GORLIN, R. A hemodynamic studv of left ventricular aneurysm. C’irctclntion, 35: 614, 1967.
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12. SOKOLO~, M. and LYON, ‘1‘. I’. The venlriculal (onplex in left ventricular hypcrtrophy as obtained by unipolar precordial and limb leads. ,1 !?l. Hecr,-t J., .37: 161, 1949. 13. JAMES, T. The Anatomy of the Coronarv Ar~(.ries. A’trw York, 1961. Paul B. Hoeber, Inc. 14. GOKLLN, 1~. Pain in the chest of sudden onset ~s\otinted with a cardiac murmur. MPT(~Englnnd 1. Med., 275: 1244, 1966. 15. DEPASQUz\LE, N. P. and BURCH, G. E. The necropsy incidence of gross scars and acute infarction of the papillary muscles of the left ventricle. rlln I. Casdiol., 17: 169, 1966. 16. HIRER, C. F., TAYLOR, D. E. M. and WADE, J. I). The effect of papillary muscle damage on atrioventricular valve function in the left heart. Jjunrt. 1. &per. Physiol., 50: 15, 1965. 17. TAYLOR, D. E. M., WADE, J. M. and HIDER, C. 1;. Heart valve lesions following papillarv nruucle damage. Nature, 207: 530, 1965. 18. HELLER, J. A., JR. and MORROW, A. G. Experimental mitral insufficiency. Szhrgery, 38: 518, 1955. 19. WOOD, P. Disease of the Heart and Circulation. I’_ 514. London, 1961. Eyre & Spottiswood. 20. COHEN, L. S., MASON, D. T. and BRAUNWALD, E Signilicance of an atria1 gallop sound in mitral regurgitation: a clue to the diagnosis of rupturc%tl chordae tendineae. Circulation, 35: 112,1967. 21. MERCER, E. N. and WALTERS, M. B. Mitral regurgitation simulating aortic stenosis. Cnnada :!4. .,I. 1.. 93: 413, 1965. 22. ESTES, E. H., DALTON, F. M., ENTMAN, M. C., DIXON, H. B. and HACKEL, D. B. The anatomy and blood supply of the papillary muscles of the left yentricle. .4m. Heart J., 71: 356, 1966. 23. ESTES, E. I-l., ENTMAN, M. L., DIXON, H. I%. ;md HACKEI., D. B. The vascular supply of the left ventricular wall. Ant. Heal-t I.. 71: 58, 1966. 24. PHILLIPS, J. H., DEPASQUALE, N. P. and BURGH, G. E. The elcctrocardiogTam in infarction of the anterolateral papillary muscle. AT)!. Heor/. 1.. 66: :138. 1963. 25. ROISFRTS, IV. C., BRAUNWALD, E. and MORROW. ,\. (;. Acute severe mitral regurgitation secondary to ruptured chordae tendineae: clinical hemodvnamic and pathologic considerations. Ci,-ccllntion. 33: 58, 1966. 26. SANDERS, C. A., AUSTEN, W. G., HARTI~ORNE, J, IV., DINshIoRE, R. E. and SCANNELL, J, G. Diagnosis and surgical treatment of mitral regurgitation secondary to ruptured chordae tendinrar. New England J. Med., 276: 943, 1967. 27. GROSS, L. The Blood Supply to the Heart in its Anatomical and Clinical Aspects. New \‘ork, 1!121. Paul B. Hoeber, Inc. 28. PROCDFIT, W. L.. CAIRLEY, E. K. and SONES, F. M., JR. Distribution of arterial lesions demonstrn ret1 by cinecoronary arteriogaphv. Circu/ation. 36: 54. 1967.