Echocardiographic studies of the mitral valve in patients with congestive cardiomyopathy and mitral regurgitation

Fundamentals of clinical cardiology

Echocardiographic studies in patients with congestive and mitral regurgitation

of the mitral valve cardiomyopathy

David K. Millward, M.D. Lambert P. McLaurin, M.D. Ernest Craige, M.D. Chapel Hill, N. C.

E

chocardiograms of the normal mitral valve (Fig. 1) demonstrate that both the anterior and posterior leaflets come together in early systole and remain approximated until the valve abruptly opens in early diastole.1 Prolapse of the mitral valve leaflet into the left atrium may be diagnosed from a typical echocardiographic finding of separation of the anterior and posterior mitral valve leaflets during ventricular systole*-4 (Fig. 2). This echocardiographic abnormality is found in patients with the systolic click-late systolic murmur syndrome,*p3 or with ruptured chordae tendineae,4a5 but is not found in mitral regurgitation resulting from rheumatic heart disease,‘j or in normal patients. Patients with nonhypertrophic or “congestive” cardiomyopathy commonly have mitral regurgitation, ‘t8 the etiology of which is obscure. In an attempt to provide further understanding of the pathogenesis of mitral regurgitation in this type of cardiomyopathy, ultrasound recordings from the mitral

valve were made and compared with similar recordings from patients with chronic mitral regurgitation caused by rheumatic heart disease and acute mitral regurgitation secondary to ruptured chordae tendineae. A group of patients with dilated left ventricles from severe aortic regurgitation were also studied. The echocardiographic finding of systolic separation of the mitral leaflets was observed in 16 of 17 patients with cardiomyopathy and 5 of 5 patients with acute mitral regurgitation due to ruptured chordae tendineae. This finding was absent in all patients with chronic rheumatic mitral regurgitation and in those with left ventricular dilatation secondary to aortic regurgitation. This evidence suggests that the mitral regurgitation in cardiomyopathy is not due to “dilatation of the mitral valve annulus” as is commonly thought,s~10 but is more likely due to systolic separation of the mitral valve leaflets or prolapse of one of them into the left atrium during ventricular systole.

From

the C. V. Richardson Laboratory and the Department of Medicine of the University of North of Medicine. Chapel Hill, N. C. 27514. Supported by National Heart and Lung Institute Grant No. HE05727 and No. HE05486, the North Association. and the Henry A. Fescue Professorship at the University of North Carolina. Received for publication April 28. 1972. Reprint requests to: Lambert P. McLaurin, M.D., North Carolina Memorial Hospital, Chapel Hill,

Vol.

85, No.

3, pp. 413-421

March,

1973

American

Carolina, Carolina

N.

Heart Journal

School Heart

C. 27514.

413

Millward, McLaurin,

414

Am. Heart I. March, 1973

and Craige

ANTERIOR LEAFLET POSTER1 OR LEAFLET

Fig. 1. Normal mitral valve echogram. The valve is closed at point C. During systole the closed mitral valve moves anteriorly until point D at which time the valve abruptly opens to its most anterior position (23). .4 indicates the peak open valve position as ;I result of atria1 contraction. Mitral valve excursion was measured as the vertical distance between D and E. The posterior leaflet is less well seen clue to its lower excursion. It is apparent, however, that both leaflets merge at point C‘ and remain in apposition throughout systole (C to D). The vertical distance between the white dots represents one centimeter of tissue.

ANTERIOR LEAP LET

Fig. 2. the mid showing leaflets (merked leaflets. represents

Mitral valve echogram from a patient with systolic click-late systolic murmllr syndrome prolapsed mitral leaflet. In early systole the approximate each other but soon separate by arrow) indicating prolapse of one of the The vertical distance between the white dots one centimeter of tissue.

Material

and methods

Thirty patients with mitral regurgitation from various causes and twelve patients with aortic regurgitation and greatly increased end-diastolic left ventricular volumes were selected for study. All patients had a mitral valve’ and a left ventricular volume echocardiogram.11-14 The clinical and echocardiographic diagnosis n-as confirmed by cardiac catheterization and left

ventricular cineangiography in 17 patients. Echo signals from the anterior and posterior leaflets of the mitral valve were obtained by previously described techniques’ using an Ekoline 20 diagnostic ultrasonoscope with a 2.25 XIHz transducer of 0.50 inch diameter. The minor axis dimension of the left ventricle was determined by ultrasound (Fig. 3) and the left ventricular end-systolic (ESV) and enddiastolic volumes (EDV) were determined from regression equations derived in our laboratory and previously reported.” From these volume measurements stroke volume (SV) and ejection fraction (EF) were computed. The anterior leaflet mitral valve excursion (hl\;E) was measured in millimeters as the vertical distance between points D and E on the mitral valve echogram (Fig. 2‘1. The rate of the initial diastolic mitral valve leaflet downslope (ARIVD) was measured in millimeters per second. All measurements were made by a technician \\:ho had no knowledge of the patients. The 42 patients were divided into four clinical groups (Table I). Group I consisted of 17 patients with “congestive” cardiomyopathy diagnosed using the criteria suggested I)y Perloff’” and Fowler.‘6 Each patient had congestive heart failure, cardiomegaly, and an abnormal ECG. All patients had a typical apical holosystolic murmur with either a left ventricular diastolic

Echocardiographic

J.W.

studies of mitral valve

415

A.G.

POST LV WALL

Fig. 3. Volume echocardiogram comparing aortic regurgitation (J. W.) and “congestive” cardiomyopathy (A. G.). DD represents the diastolic minor axis dimension measured at the peak of the R wave on the ECG. Ds represents the systolic minor axis dimension measured at the peak of the posterior wall inward movement at the end of the T wave on the ECG. Note the decrease in minor axis shortening in congestive cardiomyopathy (A. G.) indicating a decreased ejection fraction. The vertical distance between the white dots represents one centimeter of tissue.

gallop or a mid-diastolic rumble, and on this basis a diagnosis of mitral regurgitation was made. Five of the 17 patients underwent cardiac catheterization, and mitral regurgitation was confirmed angiographitally in all. None of these patients had a history of or a clinical course compatible with rheumatic heart disease, hypertension, or coronary atherosclerotic heart disease. In several patients alcoholism, infection, or the peripartum state suggested a possible etiology for the cardiomyopathy. In others, no cause for the cardiomyopathy was apparent. Group II included nine patients with chronic mitral regurgitation and a dilated left ventricle. Each of the nine patients had a history of rheumatic fever. All patients had a typical high frequency holosystolic apical murmur which was also heard in the axilla. Although none of these patients underwent cardiac catheterization, none had mitral stenosis by clinical or echocardiographic criteria.’ Group III included 12 patients with severe aortic regurgitation. Seven of these patients underwent cardiac catheterization, and four of them had clinically suspected mitral regurgitation demonstrated by left ventricular cineangiography. Each patient was found to have an end-diastolic left ventricular volume that, determined from

the echocardiogram, was at least 30 per cent greater than normal. Group IV consisted of five patients with acute mitral regurgitation. All of these patients had severe mitral regurgitation demonstrated angiographically as well as hemodynamic findings typical of acute nonrheumatic mitral regurgitation.” The diagnosis of ruptured chordae tendineae was confirmed at the time of mitral valve surgery in four of the five patients. Results

In 16 of 17 patients with “congestive” cardiomyopathy the mitral valve echogram was abnormal in that the two mitral valve leaflets never completely approximated one another during ventricular systole. This echo pattern is illustrated in Fig. 4. Both leaflets move toward each other at the end of diastole, but they never completely merge and thereby produce two echoes rather than one during systole. None of the patients with rheumatic niitral regurgitation (Group I I) or with severe volume overload due to aortic regurgitation (Group III) demonstrated separation of the valve leaflets during systole. All of the patients with acute mitral regurgitation due to ruptured chordae tendineae (Group IV) showed systolic separation of the anterior and posterior leaflets (Fig. 5).

Millward,

416

Table 1. Principal

Mclaurin,

and Craige

cl,inical and echocardiographic I

sex

data of study patients

Etiology

I Group R. B. E. H.

16 28

M M

‘,B. M. L. c. hl. A. B. R. A. J. C. A. H. B.

32 34 41 25 31 58 61 57 51 43 77 40 23 54 50

F” F F M F 31 ItI hl F M hl M M M

‘V. P. N. D. 11. S. S. \V. \V. P. h’I. E. G. I<. M.

I-Cardiomyopathy

Post myocarditis Alcoholic Alcoholic Postpartum Postpartum Postpartum Post myocarditis Idiopathic Idiopathic Idiopathic Idiopathic Idiopathic Idiopathic Idiopathic Idiopathic Idiopathic Alcoholic

Group P. .T. J. v. \v. I... A. G. F.

F. B. L. 0. H. >I. R. G. I,.

32 17 22 61 17 16 25 16 30

F hl hl ?a 31 hl h’I F F

D. P. Da. C. H. .4. H. W. Q’. F.

23 18 15 22 64 37 2.5 22 16 63

51 F M 41 RI M F F hl

2 1 1 2 2 2 1 1 3

III-Xortic

S. W. A. E. F.

30 51 59 70 23

M M M %I M

MR; ;E;

180 336 223 388 342 295 183 498 231 218 187 370 240 331

135 2.54 130 252 245 171 108 360 146 161 140 270 185 212

Mitral ,324 131 223 200 232 225 114 147 206

Mitral

3 3 3 4 3

190 260 356 318 534

lleart .\ssociation: excursion: AMVD = subacute bacterial

I

A MVD (mni./ser.)

: leaflet keparatiox

0.25 0.24 0.44 0.35 0.28 0.41 0.24 0.28 0.24 0.26 0.25 0.28 0.23 0.27

11 7 14 33 8 20 2.5 10 21 8 20 17 11 17 14 9 15

350 155 93 222 98 96 235 176 187 93 224 130 185 288 69 73 138

0 50 0.49 0.36 0.50 0.46 0.55 0.65 0.63 0.48

26 29 13 12 17 33 11 28 18

112 136 110 83 75 186 100 136 140

No

No

Regurgitation 163 67 143 88 \?5 101 44 45 106

and a dilated

IV-Acute

M J-E (mm.)

I j .systolic

Regurgitation 0.29 0.29

478 310 236 376 284 262 277 327 290 461

SBE

Mitral 300 200

3 2 3 1 3 1 2 I 2 3

RCT RCT

zIbbreviations: A.H..A. = American fraction; MVE = mitral valve :\R = aortic regurgitation; SBE

with 427 283

Regurgitation

SBE, .4R AR, MR; RHD AR, MR; RHD AR, MR; RHD Idiopathic ,4R: RHD AR: RHD Idiopathic .4R; RHD AR; syphilis

Group R. J. G. B. T.

II-Chronic

RHD RHD RHD Unknown RHD RHD RHD RHD RHD

Group L. S. I,. R. G. D. E. J. P. W.

4 3 3 3 3 3 3 4 3 4 2 3 4 4 4 4 3

I

!

204 176 139 156 175 102 158 182 140 216

h‘0 h-0 NO NO NO h-0 NO No

left Lcntricle 0.57 0.43 0.4 I 0.59 0.38 0.61 0 4.1 (1 4.i 0 52 0. 5.3

14 19 '9 21 22 17 23 19 12 15

136 147 96 77 150 192 120 81 69 103

0.53 0.52 0.39 0.59 0.53

18 13 38 17 26

142 92 158 68 112

NO

lh0 NO NO NO

No No NO

Regurgitation 90 125 206 129 213

Yes Yes \-es Yes l-es

EDV = end-diastolic volome; I’S;\’ = end-cyitolic volume. IF = ejection = anterior mitral valre leaflet downslo~~e; RHD = rheumatic heart divase; endocarditis; MR = n~itral regurgitation; RCT = ruptured chordae tendineae.

Echocardiographic

studies of mitral

valve

417

ANTERKJFZ LEAFLET p”L~E% POST LV WALL

Fig. 4. Mitral valve echogram from two patients with documented ruptured chordae tendineae. The increased excursion of the anterior leaflet is seen. During systole the leaflets fail to merge completely and multiple echo signais persist. The vertical distance between the white dots represents one centimeter of tissue.

G. A.

B.G.

Fig. 5. Mitral valve echogram in three separate patients with congestive cardiomyopathy and angiographically proved mitral regurgitation. Both anterior and posterior mitral valve leaflet echoes are seen throughout the cardiac cycle. During systole the leaflets fail to completely merge and two signals persist. Note the decreased excursion of the anterior leaflet. The vertical distance between the white dots represents one centimeter of tissue. The mitral valve echogram had a second abnormality in eleven of the sixteen patients in Group I (Patient J. W. was excluded in the analysis because of incomplete data). The average mitral valve excursion (SlVE) as measured from points D to E (Fig. 2) in this group was decreased (15 & 7 mm.) when compared to previously reported normal valves (20 to 32 mm.)18~1g or to the patients in Group II (p = 0.06) and in Group IV (p = 0.05). There was no significant difference in hlVE between Group I (cardiomyopathy) and Group 111 (severe aortic regurgitation). In an effort to explain the decreased

excursion of the mitral valve in patients with cardiomyopathy, Group I was further subdivided into 2 groups: A, I\IVE less than 20 mm., and B, JIVE more than 20 mm. The end-diastolic volume and the anterior mitral valve downslope were not significantly different between groups A and B but the ejection fraction (EF) was 0.26 f 0.05 in group A and 0.35 f 0.03 in group B (p = 0.005). The decrease in the mitral valve excursion appeared to be greatest, therefore, in the group with the most severely compromised ventricular function as measured by ejection fraction. The excursion of the anterior leaflet

418

Millward,

McLaurin,

Table I I. Group comparison

and Craige

of echo data

(

Group I Cardiomyopathy (n = 16) II

III

IV

%‘;*

1

F2.Y

;:z

) (:fl:., 170 80

51 9 0.0001

21 8 0.06

120 34 0.045

165 33 N.S.

49 8 0.0001

19 Its.

117 39 0.03

158 63 N.S.

51 7 0.0001

22 10 0.05

114 36 0.07

206 71

Chronic mitral regurgitation (n = 9)

mean S.D.* Pt

200 64

98 41

Aortic regurgitation and volume overload (n = 10)

mean SD.* Pt

330 82 N.S.

Ruptured chordae tendineae (n = 5)

mean S.D.* Pt

331 129 N.S. as in Table

1

15 7

296 94

*S.D. = standard deviation; other abbreviations t = p value comparisons with Group I.

i; 29 6

mean SD.*

,015

(

0002

I.

(RIVE) was excessive in three patients in Group IV in contrast to the situation in Group I. This finding is consistent nith angiographic observations by Wexler and associateszO showing excessive mitral valve motion in patients with ruptured chordae tendineae. Previous reports have described an increased mitral valve excursion (1\2VE) in patients with rheumatic valvulitis and mitral insufficiency, I9 but our data do not support this finding. The difference may be explained by the fact that we measured &lVE as the vertical distance between points D and E according to the method of Edler’ rather than from points C to E (Fig. 2). The initial rate of the anterior mitral valve downslope (ARIVD) was increased in mitral regurgitation associated with cardiomyopathy (Group 1) and was found to be significantly greater than in any of the other patient groups. Left ventricular end-diastolic volume, stroke volume, and ejection fraction Ivere determined in each patient by means of the echocardiographic technique (Table I). Group comparisons are shown in Table II. All of the patients \vith cardiomyopathy (Group I) had increased end-diastolic volumes and very low ejection fractions when compared to normals. The end-diastolic volumes of the patients with chronic mitral regurgitation (Group II), aortic regurgitation (Group III), and acute mitral regurgitation (Group IV) were also increased but

the ejection fractions in these patients were normal or slightly decreased (Table I). The echocardiographic measurement of the ejection fraction proved to be the best parameter for discrimination between Group I and the other groups of patients (p < 0.0001). Discussion

The echocardiographic finding of systolic separation of the mitral valve leaflets has been shown to be a characteristic sign for prolapse of one of the leaflets.2-5This observation has also been recently reported in patients with flail leaflets due to ruptured chordae tendineae.5 In both instances the echocardiographic findings have been substantiated by correlation with angiographic studies.3,5WC also found systolic separation of the mitral valve leaflets utilizing echocardiography in each of five patients with ruptured chordae tendineae supporting the above conclusion. Similarly patients with non-hypertrophic or “congestive” cardiomyopathy demonstrated a failure of the anterior and posterior mitral valve leaflet echoes to come together during systole. This observation strongly suggests that valve leaflet separation or even prolapse is the cause of mitral regurgitation in these patients. All of the conditions previously associated with mitral valve prolapse have had an abnormality of the mitra1 valve supporting structures-either in the papillary muscles,

Echocardiographic

the chordae tendineae, or in both.*-” There are several pathophysiologic mechanisms to be considered as potential causes for the malfunction of the mitral apparatus in congestive cardiomyopathy. These include: (1) a mechanical derangement of the mitral supporting structures due to ventricular dilatation,21~22 (2) a pathologic abnormality of the papillary muscles due to a disease process,6J3-z6 and (3) papillary muscle dysfunction caused by subendocardial ischemia. The common explanation for mitral regurgitation in cardiomyopathy is dilatation of the mitral valve annulus.9Jn Measurements of the mitral valve annulus in patients with nonhypertrophic cardiomyopathy are not available, but it is our impression from examining a small number of hearts that the mitral annulus is not dilated in this condition. Robertsz’ is also of the opinion that dilatation of the mitral annulus occurs very infrequently if not rarely in “congestive” cardiomyopathy. Burch and associateP also have questioned the explanation that simple dilatation of the annulus accounts for mitral regurgitation in conditions associated with left ventricular dilatation. They point out that the dense fibrous tissue comprising the mitral annulus is not easily distended, that the surface area of the valve leaflets is approximately 2.5 times greater than the area of the valve orifice, and that during systole the annulus is contracted?* The same authors22 state that papillary muscle dysfunction arises from an abnormal spatial orientation of the papillary muscles, and that this is the probable cause of mitral regurgitation in cardiomyopathy. The absence of echocardiographic features of mitral valve leaflet systolic separation in patients with high left ventricular end-diastolic volumes due to aortic regurgitation suggests that ventricular dilatation alone is not sufficient to produce papillary muscle dysfunction. This finding, however, does not exclude the possibility that ventricular dilatation in “congestive” cardiomyopathy contributes to the functional papillary muscle abnormality. Levy and EdwardP have found that in aortic regurgitation the left ventricle enlarges predominantly along its long axis. This is in contrast to the situation in “congestive”

studies of mitral valve

419

cardiomyopathy, where the ventricle dilates in all planes and assumes a more spherical configuration.21f28 The result of this difference is that in aortic regurgitation the papillary muscles are pulled down away from the mitral valve, but the advantageous longitudinal orientation is partly maintained. Fibrosis or any other pathologic process that affects the myocardium should involve the papillary muscles, since these structures are extensions of the left ventricular muscle. This has been shown to be true in coronary atherosclerosis23-25~2s~30 and in a variety of cardiomyopathic conditions.36 The blood supply of the papillary muscles has been shown to be an extension of the subendocardial blood ~upply.~~ In patients with cardiomyopathy and left ventricular dysfunction, the left ventricular end-diastolic volume and pressure are severely elevated,31a32 leading to an increase in intramyocardial tension or diastolic wall stress31 which, in turn, decreases the coronary blood flow to the subendocardial areas, particularly the papillary muscles.33 It would therefore not be surprising if, in states of cardiac decompensation with increased left ventricular diastolic volume and pressure, the papillary muscles failed to contract properly. None of the above processes is mutually exclusive of the others, and it is probable that in different patients several or all of the above mechanisms may be operative. Delineation of the specific functional abnormality in all the types of mitral regurgitation is beyond the scope of this investigation, but it appears from our echocardiographic data that the mitral regurgitation in “congestive” cardiomyopathy results from an abnormality of papillary muscle function and is not simply due to dilatation of the mitral valve annulus. In ruptured chordae tendineae the echocardiogram shows systolic separation of the mitral leaflets which is consistent with leaflet prolapse. This echocardiographic sign was not seen in those patients lvith chronic mitral regurgitation where the abnormality is in the leaflets rather than in the supporting structures. Angiographic studies support these echocardiographic observations.3,“,19 Because this echocardiographic sign lacks specificity, an effort was made to find other mitral valve abnormali-

420

k?illward,

McLu~in,

rind Craige

ties that might separate those patients with cardiomyopathp from those with ruptured chordae tendineae. Cardiomyopathy patients were found to have an almormall>low mitral valve excursion (lI\‘E) and an increased anterior mitral valve diastolic do\\-nslope (A>I\‘D) \\hen compared to the other groups (Tables I and II). The quantitative left ventricular volume measurements and estimates of ejection fraction using the echocardiogram &on-ed that the patients with cardiomyopathy all had significantly increased left ventricular enddiastolic volumes and diminished ejection fractions (Tables I and II). This was in contrast to those patients with ruptured chordae tendineae, all but one of whom had normal ejection fractions. Decreased excursion of the mitral valve leaflet was associated with a low ejection fraction in the cardiomyopathy patients. A possible explanation for this association could lie that there Iv-as incomplete opening of the valve due to the large residual diastolic volume. Although the valve leaflets appear to prolapse beyond the usual plane of the closed mitral valve, total excursion of the leaflets is reduced in the cardiomyopathy patients as compared to the patients \vith ruptured chordae tendineae. The increase in anterior mitral valve leaflet downslope in this group of patients may IX accounted for l)y the inability of the papillary muscles to retard the rate of closure during earlv diastole. Such a mechanism has been previously proposed to account for a similar observation in patients with myocardial infarction and papillary muscle dysfunction .34 These echocardiographic findings-systolic separation of the mitral valve leaflets, a decreased mitral valve excursion, and an increased anterior mitral valve donnslope together are strongly suggestive of a diagnosis of “congestive” cardiomyopathy. The mitral valve abnormalities, together with a decreased echo ejection fraction are positive ol)jective findings that can be simplv obtained in order to make a diagnosis of cardiomyopathy. Echocardiography, therefore, is a useful technique in the differential diagnosis of conditions affecting the mitral complex. Summary This echocardiographic strated that the finding

study has demonof systolic separa-

tion of the mitral leaflets is not specific for those patients with the late systolic clicklate systolic murmur syndrome l>ltt is also seen with ruptured chordae tendineae and in cardiomyopathy patients lvith mitral regurgitation. From these observations and with the help of 01,servations of others, ne have reasoned that the mitral regurgitation associated \\-itll cardiomyopathy is not due to mitral annulus dilatation Ijut to papillary muscle dysfunction. The authors would like to thank Sally hloos and Gwen Garner for technical assistance, Elizabeth Phillips for typing the manuscript, and Dr. Nicholas J. Fortuin for his review of the paper. REFERENCES 1. Edler, I.: Utrasoundcardiography, Actn Med. Scand. 170 (Suppl.) :370, 1961. 2. Kerber, R. E., Isaeff, P. RI., and Hancock, E. {VI’.: Echocardiographic patterns in patients with the syndrome of systolic click and late systolic murmur, N. Engl. J. Med. 284:691, 1971. L7 Dillon, J, C., IHaine, C. L., Chang, S., and FeiKenbnum, H.: Use of echocardiography in patients with prolapsed mitral valve, Circulation 43:503, 1971. 4. Shah, P. M., and Gramiak, Ii. : Echocardiographic recognition of mitral valve prolapse, Circulation 42 (Suppl. II I) :&5, 1970. 5. Duchak, J. RI., Chang, S., and Feigenbaum, H.: Echocardiographic features of torn chordae tendineae, (Abstr.)Am. J. Cardiol. 29:260, 1972. 6. Joyner, C. R., Reid, J. M., and Bond, J, P.: Reflected ultrasound in the assessment of mitral valve disease, Circulation 27:503, 1963. 7. Massumi, 11. A., Rios, J. C., and Gooch, A. 5.: Primary myocardial disease. Report of fifty cases and review of the subject, Circulation 31:19, 1965. 8. Dye, C. I .,., Rosenbaum, D., Lowe, J. C., Behnke, R. H., and Genovese, I’. D.: Primary myocnrdial disease, Ann. Intern. Med. S8:426. 1963. 9. Friedberg, C. K.: Diseases of the heart, Philadelphia, 1970, W. B. Saunders Company, p. 1030. 10. Hursl, J. IV., and Logue, R. B.: The heart, New York, 1970, McGraw-Hill Book Company, p, 814. 11. Fortuin, N. J., Hood, W. P., Sherman, IV. E., and Craige, E.: Determination of left ventricular volumes by ultrasound, Circulation M:575, 1971. 12. Popp, R. I.., U’olfe, S. B., Hinnto, ‘I‘., and FeiKenbaum, H.: Estimation of right and left . ventricular size of ultrasound, Am: J. Cardiol. 24:523, 1969. 13. Feiqenbaum. H., Wolfe, S. B., Popp. K. L., et al.: Correlation of ultrasound with angiography in measuring left ventricular dias%oiic volume, Am. J. Cardiol. 23:111, 1969. 14. Pombo, J. F., Troy, B. L., and Russell, R. 0.:

Echocardiographic

15. 16.

17.

18.

19.

20.

21.

22.

23.

24.

Measurement of left ventricular volumes and ejection fraction by echocardiography, Circulation 43:480, 1971. Perloff, J. K.: The cardiomyopathies-current perspectives, Circulation 44:942, 1971. Fowler, N. 0.: Differential diagnosis of cardiomyopathies, Progr. Cardiovasc. Dis. 14:113, 1971. Klughaupt, M., Flamm, M. D., Hancock, E. LV., and Harrison, D. C.: Nonrheumatic mitral insufficiency, Circulation 39:307, 1969. Segnl, B. I,., Likoff, W., and Kingsley, B.: Echocardiography: Clinical application in mitral regurgitation, Am. J. Cardiol. 19:50, 1967. \Vharton, C. F. P., and Bescos, L. L.: Mitral valve movement: A study using an ultrasound technique, Br. Heart J. 32:344, 1970. \Vexler, L., Silverman, J. F., DeBusk, R. F., and Harrison, D. C.: Angiographic features of rheumatic and nonrheumatic mitral regurgitation, Circulation 44:1080, 1971. Levy, M. J., and Edwards, J. E.: Anatomy of mitral insufficiency, Progr. Cardiovasc. Dis. 5:119, 1962. Burch, G. E., DePasquale, N. P., and Phillips, J. H.: The syndrome of papillary muscle dysfunction, ALI. HEART J. 75:399, 1968. DePasquale, N. P., and Burch, G. E.: The necropsies incidence of gross scars or acute infarction of the papillary muscles of the left ventricle, Am. J. Cardiol. 17:169, 1966. Arosemena,E.,Moller, J.H., and Edwards, J.E.: Scarring of the papillary muscles in left ventricular hypertrophy, AM. HEART J. 74:446, 1967.

25.

26.

27. 28.

29.

30.

31.

32.

33.

34.

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Cohen, L. S., and Roberts, R’. C.: The clinical spectrum of mitral regurgitation caused by malfunction of the papillary muscles or fibrosis of the left ventricular free wall, Circulation 38 (Suppl. 6):57, 1968. Marcus, F. I., Gomez, L., Glancy, D. L., Ewy, G. A., and Roberts, \V. C.: Papillary muscle fibrosis in primary myocardial disease, AM. HEART J. 77:681, 1969. Roberts, IV. C.: Personal communication, 1972. Hood, W. P., Jr., and Rolett, E. L.: Patterns of contraction in the human left ventricle, Circulation 40 (Suppl. 111):109, 1969. Burch, G. E., DePasquale, N. P., and Phillips, J. H.: Clinical manifestations of papillary muscle dvsfunction. Arch. Intern. Med. 112:112. 1963: 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, AM. HEART J. 71:356, 1966. Hood, \I’. P., Jr., Rackley, C. E., and Rolett, E. L.: Wall stress in the normal and hypertrophied human left ventricle, Am. J. Cardiol. 22:550, 1968. Rackley, C. E., Hood, W. P., Jr., Rolett, E. L., and Young, D. T. : Left ventricular end-diastolic pressure in chronic heart disease, Am. J. Med. 4‘8:310, 1970. Salisbury, P. F., Cross, C. E., and Rieben, P. A.: Acute ischemia of inner layers of ventricular wall, Aal. HEART J. 66:650, 1963. Tallury, V. K., DePasquale, N. P., and Burch, G. E.: The echocardiogram in papillary muscle dysfunction, A&f. HEART J. 83:12, 1972.