TOTAL MITRAL VALVE REPLACEMENT: LATE RESULT

TOTAL MITRAL VALVE REPLACEMENT: LATE RESULT Viking Olov Bjork, M.D., and Elis Malers, M.D., Uppsala,

Sweden

T

HE total mitral valve replacement by the Starr-Edwards ball valve prosthe­ sis8- 9 is performed only when an annuloplastic procedure has been proved or is thought to be unsuitable. The purpose of this paper is to report the results in 19 patients who were followed up to 2 years after operation. MATERIAL

There were 12 women and 7 men. The oldest patient was 59 years of age and the youngest patient 34 years, the average age was 43 years. The degree of mitral insufficiency was evaluated in all cases by left ventricular angiography. 2 The contrast medium injected into the left ventricle outlined the left atrium before or when the contrast material reached the middle of the ascending aorta (degree I and I I ) in 9 cases, when it reached the arch of the aorta (degree I I I ) in 5 cases, and to the middle of the descending aorta (degree IV) in 5 cases. Aortic insufficiency, preoperatively evaluated also by thoracic aortography, was surgically verified in 5 cases, and tricuspid stenosis and insufficiency in one case each. METHODS AT OPERATION

Surgical Technique.—The right-sided approach was used in most cases, although the left-sided was preferred for re-operation when it was obvious before the operation that a total valve replacement would have to be performed. Both the anterior and the mural leaflets with the two papillary muscles were resected. In the case of contracted fibrous and calcific mitral ostia, it was considered that the pumping function of the heart could not be improved by leaving the papillary muscles. Furthermore, excision of the papillary muscles as well as both cusps facilitated the introduction of a large prosthesis in cases of a combination of mitral insufficiency and stenosis. No. 2 silk sutures were used for fixation of the prosthesis; care was taken to place the sutures so that the knots were buried under the remnant edges of the valvular tissue. The prosthesis was kept incompetent by a special holder during the fixation in order to prevent air embolism. Prom the Departments of Thoracic Surgery (Head: V. O. Bjork, M.D.) and Internal Medi­ cine (Head: E. Ask-Upmark, M.D.), University Hospital, Uppsala, Sweden. Received for publication Jan. 20, 1964. 625

B J 8 K K AND MALEES

626

TABLE I.

J. Thoracic and Cardiovas. Surg.

N I N E P A T I E N T S D I E D OF 19

W H O UNDERWENT TOTAL VALVE PRESSURES

TOTAL (ML.)

RELATIVE (ML./ SQ. M . )

HEART WEIGHT AT AUTOPSY (GRAMS)

1,700

1,000

HEART SIZE

NO.

AGE (YR.)

1

47

M I + MS + AI + TI

2

46

MI + AI

49

1,400

3

48

M I + MS reop.

71

4

44

M I + MS + AI

5

46

6

REST

EXER­ CISE

620

75

100

15

25

950

500

50

85

27

38

1,740

940

700

80

106

29

—

40

4,500

3,200

620

50

—

M I + MS reop.

47

780

560

550

28

40

11

—

47

MI

54

4,000

2,500

930

35

53

16

—

7

38

M I + MS

70

1,690

915

690

38

72

25

30

8

43

M I + MS

53

2,700

1,700

690

31

76

17

25

9

36

M I + MS

80

1,020

550

25

48

15

25

'Legend:

WEIGHT

PULMONARY AR­ PULMONARY ARTERY ( S Y S T . ) TERY ( W E D G E )

DIAGNOSIS*

(go.) 60

EXER­ CISE

—

M 1770 M 1370 M 46 M 73 M 19 M 660 M 29 (780(550(25(500(40(11(253,200) 80) 4500) 930) 29) 38) 106) MI—mitral insuffleiency; MS—mitral stenosis ; AI—aortic insufficiency; TI—tricuspid

Perfusion.—The average perfusion time was 77 minutes (range 61 to 116 minutes). Longer periods of aortic occlusion had to be used in 4 cases (19 to 56 minutes) and for 2 to 3 minutes in 4 cases. Treatment With Anticoagulants After the Operation.—Anticoagulants were not given to 7 patients, all of whom died; 6 died at operation or in the imme­ diate postoperative period, the remaining one later on. Systemic embolism preceded the death of 3 of these patients, one additional patient died from coronary embolism 4 months after the operation. Anticoagulant therapy was given to the 12 remaining patients; it was instituted 1 to 4 months after operation in 3 patients, 15 to 16 days after operation in 2 patients, and 3 to 6 days postoperatively in 7 patients (in one after the occurrence of cerebral embolism). METHODS OF INVESTIGATION

The general clinical investigation included determination of the heart size and physical working capacity (kpm./min.). This was done before operation, at a first follow-up 6 months to 1 year after operation, and at a second follow-up 2 years after operation. Right heart catheterization, with determination of

TOTAL MITRAL VALVE EEPLACEMENT

Vol. 48, N o . 4 October, 1964

627

REPLACEMENT W I T H THE STARR-EDWARDS BALL VALVE P R O S T H E S I S (MM.

Hg)

L E F T ATRIAL ( M E A N ) AT OPERATION

WORKING CAPACITY (KPM./ MIN.)

ANGIOGRAPHIC DEGREE

OP M I

COMMENTS

55

27

150

II

Died after 1 day, myocardial failure

48

—

250

II

Died on table, myocardial failure; A I impaired ball valve function

44

22

150

IV

34

25

150

II

42

30

250

II

Died after 4 mo. from coronary embolism, thrombosis on atrial side of prosthesis; no anticoagulant treatment

36

24

50

II

Died 7th day after hemiplegia occurred 1st day postop.; thrombosis on atrial side of prosthesis

25

16

150

I

Died after 36 days with hemiplegia and multiple embo­ lism during effective anticoagulant treatment

38

30

200

III

Died after 2 days of multiple embolisms, thrombosis on atrial side of prosthesis

9

14

600

IV

Cerebral embolism with a partial hemiplegia, 2 days postop., then died after 8 mo. from a recurrent em­ bolism treated with anticoagulant

M 37 (9-48)

M 24 (14-30)

Died on table, myocardial failure + pulmonary fibrosis Died 7th day, myocardial failure

M 216 (50600)

insufficiency.

pressures and flows, was performed at rest and, as a rule, during exercise as well in all patients before operation and at the first re-examination 6 months to 1 year postoperatively. Left ventricular catheterization was done in all patients preoperatively with pressure measurements and angiocardiography. This investigation was repeated at the second re-examination (2 years after operation) in only 5 patients. In 2 of these 5 patients, the left atrial and left ventricular pressures were recorded simultaneously in order to detect a possible diastolic gradient over the mitral orifice at rest. Left ventricular angiocardi­ ography was then added in order to study the left ventricular function and the competence of the Starr-Edwards ball valve prosthesis. The 10 surviving patients were also examined with regard to a possible intravasal hemolysis caused by the ball valve prosthesis. Values of hemoglobin, reticulocytes, bilirubin, haptoglobin, and serum iron were determined in the blood. Coombs' test was also performed. RESULTS

Deaths.—Nine of 19 patients had died before the time of the re-examination. There were 7 hospital deaths and 2 late deaths. The clinical, hemodynamic, and

628

BJoRK AND

MALERS

J. Thoracic and Cardiovas, Surg.

angiocardiographic findings in these cases are summarized in Table I. Four patients died from myocardial failure, one on the operating table and one each on the first, second, and seventh postoperative days. The patient who died on the operating table had a significant aortic insufficiency which pushed the mitral ball backward during diastole with a resulting functional mitral stenosis. The remaining 5 patients died from systemic embolism originating from thrombosis over the base of the prosthesis in the left atrium. Two patients (Nos. 6 and 8) died on the second and seventh day after the operation; neither of these had been treated with anticoagulants. The patient who died on the thirty-sixth day after operation (No. 7) had been treated with anticoagulants and, in spite of thrombotest values varying from 10 to 25 per cent during 10 days previously, embolism to most organs occurred. The patient who died after 8 months (No. 9) from a recurrent cerebral embolism was also treated with anticoagulants but only under the guidance of the prothrombin index. Her first embolic episode occurred 2 days postoperatively before anticoagulant treatment had been given. The patient who died after 4 months (No. 5) from a coronary embolism had never been treated with anticoagulants. As a rule, all of the 7 patients who died in the hospital showed higher values of heart volume and pressures than those who survived (see Tables I and I I I ) . They all had very large hearts, more than 900 ml. per square meter of body surface area; the largest was 3,200 ml. per square meter because of a giant left atrium. Complications.—The most frequent complication encountered was systemic embolism which occurred in more than half of the patients (one had two embolic episodes), that is, 10 of 19 cases (Table I I ) . Five patients died from embolism as just mentioned, 2 are living with severe symptoms of hemiplegia, 1 with slight cerebral symptoms, and 2 without sequelae. Two of the 5 surviving patients (Nos. 10 and 12) experienced this com­ plication before they had received anticoagulants. The 3 remaining patients were on this therapy, which in 2 cases (Nos. 13 and 17) proved to be inadequate; thrombotest values in both cases was between 46 to 35 per cent. The treatment was only guided by the prothrombin index in the last patient (No. 16). Patients With No Improvement.—The findings at the follow-up examina­ tions in the 10 surviving patients are listed in Table III. Two patients (Nos. 16 and 17) were on the whole as much incapacitated after operation as before because of severe remaining symptoms of hemiplegia. The heart function showed significant improvement in one of these cases (No. 16). One additional patient (No. 10) was slightly improved at the first follow-up 6 months after operation, but was not improved 2 years after operation because of a significant myocardial factor present before and after the operation. Patients With Improvement.—Seven of the 10 surviving patients are con­ sidered to be much improved. The findings before and after operation are summarized in Table I I I . An apical systolic murmur (Grade 3) could be heard in one case (No. 18) and was verified by left ventricular angiocardiography as due to a very slight mitral insufficiency. This was the only patient in our series who showed mitral insufficiency after operation. The heart volume had decreased

Vol. 48, No. 4

TOTAL MTTRAL VALVE R E P L A C E M E N T

October, 1964

TABLE I I .

COMPLICATION

OF EMBOLISM AFTER TOTAL MITRAL VALVE REPLACEMENT P A T I E N T S OF 19 TIME OF

NO. CASES

° ^

TOTAL

(ML./ SQ. M.)

629

TION AFTER OPERATION

T Y P E OF EMBOLUS

THROM-

ANTICO-

PROSTHESIS

TREATMENT

IN

10

RESULT

1 day

Cerebral

+

-

36 days

Cerebral

+

+

Died

1 day

Renal + Mesenteric

+

-

Died (2nd day)

550

2 days + 8 mo.

Cerebral

+

Died after 8 mo., recurrent cerebral embolism

1,120

680

Immedi­ Cerebral ately af­ ter opera­ tion

12

1,270

660

4 mo.

Cerebral

-

Living 2 % yr. without symptoms

13

930

590

21 days

Cerebral

-

Living 2 yr. with hemiplegia

16

810

580

4 mo.

Cerebral

+

Living 1% yr. with slight cerebral symptoms

17

1,410

810

1 mo.

Cerebral

+

Living 1% yr. with hemiplegia

5

780

560

6

4,000

2,500

7

1,690

915

8

2,700

1,700

9

1,020

10

4 mo.

Coronary

+

Died Died (7th day)

Living 2 yr. with­ out sequelae

in these patients; the decrease was significant in most of them. The physical working capacity was improved, with corresponding subjective improvement of the heart function. The hemodynamic findings, obtained at the first follow-up (6 months to 1 year after operation), were, as a rule, quite normal at rest. The pulmonary artery wedge mean pressure, recorded in 5 of the 7 improved patients, was normal at rest in 4 cases and slightly elevated (15 mm. Hg) in the remaining case (No. 18). Some degree of myocardial dysfunction was considered to be present in this case as judged from clinical findings. During exercise, however, this pressure was increased (18 to 28 mm. Hg) in the 4 improved patients, 3 of whom showed normal values at rest. The pulmonary arterial pressure at rest was normal in 6 of the 7 improved patients. The increase during exercise was, as a rule, less at the re-examination than before operation, the flow values as a rule were higher. In 2 of the 7 improved patients, the left atrial and left ventricular pressures were recorded simultaneously in order to determine a possible diastolic pressure gradient over the mitral orifice. The left atrial pressure at rest, measured just before the atrial contraction (a wave), was 15 mm. Hg, and the left ventricular end-diastolic pressure, measured just before the presystolic pressure rise, was 12 mm. in one case (No. 16) of sinus rhythm. This patient exhibited ventricular

BJOEK AND MALERS

630

J. Thoracic and Cardiovas. Surg. TABLE III.

PRESSURES (MM. H g )

HEART SIZE

NO.

10 11

12

AGE

DIAGNOSIS

M I + MS + 50 calcium 2U yr. follow-up MI 34 2 yr. follow-up 49

M I + MS + calcium

M I + MS 40 2 yr. follow-up

M I + MS + calcium reop. 2 yr. follow-up 15 45 M I + MS 2 yr. follow-up 14

16

51

M I + MS + 37 AI 1% yr. follow-up

M I + MS + hyperten17 59 sion 1% yr. follow-up 18

M I + MS 44 1 yr. follow-up

M I + MS + TS + A I 19 38 reop. 1 yr. follow-up Mean before

Mean after

PULM. ART. SYST.

PULM. ART. WEDGE

WEIGHT (KG.)

TOTAL (ML.)

RELA­ TIVE (ML./ SQ M.)

53

1,120 1,075

680 630

37 28

90 60

22 14

—

60

1,300 1,190

790 680

21 15

60 50

10 6

18

60

1,270

660

47

70

21

54

REST

EXERCISE

REST

EXER­ CISE

1,120

610

22

54

930 620

590 430

35 30

56

1,180

700

57

2 yr. follow-up 13

P A T I E N T S W H O SURVIVED

110

43

LEFT ATRIAL BEFORE AFTER

35

36

—

—

25

24

32

36

21

9

20

—

—

15

—

35

25

20

—

40

31

1,060

630

40

75

10

25

—

—

58

800 660

480 390

25 30

50 55

10 12

23

30

24

45

810 935

580 550

25 24

—

45

10 7

.—.

45

33

65

1,410 1,330

810 910

48 38

75

15 18

—

—

—

62

980 850

610 540

22 29

47 50

9 15

28 28

24

20

—

—

50

7

37

34

1,270 1,130 1,110 (8001,410)

830 690 675 (480830)

39 (2170)

72 (47110)

17 (934)

33 (2043)

1,070 (6602,300)

655 (3901,420)

28 (1540)

56 (4575)

11 (618)

20 (728)

70

—

36

14

—

32 (1445)

31

20

—

27 (2036)

♦Pressures and flow measured % to 1 yr. after operation; clinical data are from last follow-up.

extrasystoles in bigemina during this investigation, which probably caused an increase in the pressures (the left atrial mean pressure at regular sinus rhythm was 13 mm. Hg, and during arrhythmia was 22 mm. H g ) . The values of left atrial and left ventricular pressures were 9 mm. Hg (mean pressure being 13 mm.) and 8 mm. Hg, respectively, in the second patient (No. 14) with atrial fibrillation (left atrial pressure being measured just before the c wave, left ventricular pressure measured just before the isometric contraction of the left

TOTAL MITRAL VALVE REPLACEMENT

Vol. 4 8 , N o . 4 October, 1964 TOTAL MITRAL VALVE

REPLACEMENT*

CARDIAC OUTPUT (L./MIN.) REST

631

EXERCISE

WORKING CAPACITY (KPM./ MIN.)

ANGIOGRAPHIC DEGREE OP M I

—

IV

Not improved; myocardial disease, cerebral embolism without sequelae

4.6 3.4

6.4 4.3

500 250

4.4 7.3

8.6 14.1

900 750

I

Excellent objective and subjective improve­ ment

4.2

5.1

450

III

3.2

—

Cerebral embolism 4 mo. postop. without re­ maining symptoms; now working full time, much improved

6.1

650

2.9 4.1

6.4

50 150

II

Hemiplegia with depression; can walk, heart improved

3.5

5.1

250

II

Excellent after 2 yr.

4.2

5.8

400

—

3.7 3.7

6.1 6.1

300 350

IV

Excellent after 2 yr.

3.8 2.6

4.2

50 300

III

Hemiplegia 4 mo. postop., under anticoagu­ lant treatment; slow cerebration remaining, other symptoms disappeared, heart improved

4.2 3.3

5.3

150

III

Hemiplegia postop., under anticoagulant treat­ ment; slightly improved, ischemie heart disease

3.7 5.1

5.4 5.0

150 200

IV VII

Improved but remaining systolic murmur

300 400

III

Excellent improvement after reop. for recur­ rent M I after annuloplasty

4.2 3.9 (2.94.6) 4.1 (2.67.3)

6.0 (5.18.6) 6.5 (4.214.1)

310 (50-900) 380 (150-750)

ventricle). Thus, there was no significant diastolic pressure gradient present over the mitral orifice at rest in these 2 cases. Test for Hemolysis.—The laboratory findings with regard to intravasal hemolysis in the 10 surviving patients are listed in Table IV. The values for bilirubin given are the mean values of duplicate determinations. Low haptoglobin values, as a rule below 10 mg. per cent (normal values 30 to 190 mg. per cent), were noted in all patients except one. Increased values of reticulocytes

632

BJOEK AND MALERS

TABLE IV.

CASE NO.

J. Thoracic and Cardiovas. Surj.'.

LABORATORY F I N D I N G S AT RE-EXAMINATION W I T H REGARD TO H E M O L Y S I S IN P A T I E N T S W I T H TOTAL MITRAL VALVE REPLACEMENT HEMO­ GLOBIN (GM./ 100 ML.)

RETICULOOYTES

(%)

BILIRUBIN (MG./ 100 ML.)

HAPTOGLOBIN (MG./

10

SERUM IRON

W

COOMBS'

TEST 100 ML.) 100 ML.) Neg. 48 88 ]() M 14.9 1.4-2.4 0.4 15.2 0.4 8 70 Neg.* 11 M 0.8-2.4 Neg. 12 14.2 1.4-2.0 0.5 7-10 99 M 12.0 0.6-0.6 0.5 9 85 Neg. 13 F 14.2 0.5 6-6 Neg. 14 M 1.2-1.4 — 14.2 0.5 Neg. 15 F 2.0-3.2 7-8 75 16 12.8 1.6 1.1 0 83 Neg. F 13.7 0.5 10-11 Neg. 17 F 0.6-1.0 — 13.6 0.5 Neg. 18 F 1.0-2.4 6-0 40 19 11.6 1.4-3.4 0.8 8-7 40 Neg. F * Coombs' test was transient positive at the first re-examination (% year after operation) ; a transient autoantibody red cell formation (auto-c) was noted (HJelm, M., et al., Vox Sanguinis). (In press.) SEX

in blood were present in five single determinations in 5 patients. In Case 11 there was a transient positive Coombs' test (Table I V ) . All the other laboratory data were normal. DISCUSSION

Annuloplasty is the surgical method to be recommended in the treatment of mitral insufficiency whenever it is possible. However, it is necessary to have a prosthesis for total valve replacement at hand. The Starr-Edwards ball valve prosthesis is so far the best available. The mortality rate of 9 of 19 patients, dead one year after operation, was somewhat higher in our series when compared with that reported by others. 4-6 ' 10 The explanation for this is probably that our series included patients in a more advanced stage of disease. Thus, 3 patients who did not survive had a giant left atrium with a total heart volume varying between 2,500 and 4,500 ml. (1,700 to 3,200 ml. per square meter body surface area). The late results (2 years follow-up) were similar to those reported by Starr. 10 The risk of systemic embolism was very high; that is, 10 (5 of whom died) of 19 patients showed this complication. The findings reported earlier in an experimental series in animals have demonstrated this risk. 8 This complication seems to be difficult to avoid when it occurs at operation or in the immediate postoperative period. It occurred within 2 days after operation in 4 of the 10 patients, before the anticoagulant therapy had been started. The incidence of late systemic embolism may be easier to lessen by adequate anticoagulant therapy. 1 ' 3 ' 7 There were 7 late systemic embolisms (recurrent in one case), 5 of which occurred during anticoagulant treatment. This therapy was proved to be adequate in only one of these 5 patients. In 2 additional patients it proved to be inadequate, which probably was the factor also in the 2 remaining patients, the dosage being guided only by the prothrombin index. Thus, there were 11 embolic episodes in the whole series in 10 patients, only one of whom had been adequately treated with anticoagulants. As a result,

TOTAL MITRAL VALVE R E P L A C E M E N T

Vol. 48, No. 4 October, 1964

633

TABLE V. VALUES OF PULMONARY ARTERY WEDGE M E A N PRESSURE ( P A W ) AND F L O W S AT R E S T AND DURING EXERCISE IN P A T I E N T S W I T H TOTAL VALVE REPLACEMENT

OBSERVATION MADE

At rest

During

exercise

NO. OF CASES

PAW MEAN PRESSURE (MM. H g )

FLOW VALUES (L./MIN.)

5

Mean 9 Range 6-12

Mean 4.2 Range 2.6-7.3

3*

Mean 16 Range 14-18

Mean 3.9 Range 3.3-5.1

1

7

4.2

Mean 7.6 Mean 23 Range 5.4-14.1 Range 18-28 ♦This group includes 2 patients (Nos. 19 and 17) with a significant myocardial factor diagnosed before operation; in the remaining patient (No. 18) it was only suspected. tThis group includes 2 patients (Nos. 12 and 18) with a suspected myocardial dysfunction preoperatively. 4t

the treatment with anticoagulants, effective in preventing systemic embolism according to clinical experience, 1 ' 7 should be instituted as soon as possible after operation. The thrombotest method, being more reliable, should be used in the control of the treatment, with the values kept between 10 and 25 per cent. The hydraulic function of the ball valve prosthesis was found to be satis­ factory in patients who survived the operation. No significant diastolic gradient over the mitral orifice was noted at rest in 2 patients 2 years after operation, in whom measurements of the left atrial and left ventricular pressures were performed simultaneously. However, increased pulmonary artery wedge mean pressures were noted at rest and during exercise in some patients who had undergone operation. A comparison between the pressure and flow values ob­ tained 6 months to 1 year after operation is made in Table V in order to assess the role of the left ventricular function and that of the ball valve prosthesis in this connection. Normal pressures are found at flow values up to 7.3 L. per minute, i.e., the ball valve prosthesis causes no diastolic gradient over the mitral orifice at flows of these values. All the patients with slightly increased pulmonary artery wedge pressures at rest and at lower flow values had or were considered to have a significant myocardial factor already before the operation. The pulmonary artery wedge pressure was recorded in 5 patients during exercise, and was elevated in 4 of them. The cardiac output was lower than 7.3 L. per minute in 3 of these 4 cases. Thus, some degree of left ventricular failure was probably present in these 3 patients (in 2 of whom it had already been suspected to be present preoperatively). In the remaining case of only a slight elevation of this pressure (18 mm. Hg) at a high cardiac output (14.1 L./min.), this pressure increase may have been caused either by some degree of left ventricular failure during exercise or by the ball valve prosthesis giving a diastolic pressure gradient at this high flow value. There was no proved hemolysis present 1 to 2 years after operation in any patients with a ball valve prosthesis. However, 9 of the 10 surviving patients showed low haptoglobin values which may signify a slight subclinical hemolysis. If present, such a slight hemolysis will probably not be of significance in the future welfare of these patients.

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J. Thoracic and Cardiovas. Surg.

In conclusion, the indications for the use of the ball valve prosthesis must at the present time be very strict. The incidence of systemic embolism is very high. The function of the prosthesis is good, but it may cause a diastolic pressure gradient over the mitral valve during exercise in the presence of a high cardiac output. SUMMARY

Total valve replacement with the Starr-Edwards ball valve prosthesis is at present the best method available for the surgical treatment of a severely damaged mitral valve in instances in which the surgical method of annuloplasty cannot give a good functional result. The mortality is high in this group of patients, especially in those with a very large heart. The high incidence of embolic complications necessitates strict limitation to patients in whom it is judged that annuloplasty would fail. It is, however, encouraging that a good valvular function has been obtained in patients surviving for periods up to 2 years. Significant intravasal hemolysis caused by the ball valve prosthesis has not been observed. REFERENCES 1. Askey, J . M.: Embolism and Atrial Fibrillation, Am. J . Cardiol. 9: 491, 1962. 2. Bjork, V. O., Lodin, H., and Malers, E . : The Evaluation of the Degree of Mitral Insufficiency by Selective Left Ventricular Angiocardiography, Am. Heart J . 60: 691, 1960. 3. Borehgrevink, C. F . : Long-Term Anticoagulant Therapy in Angina Pectoris and Myocardial Infarction, Acta med. scandinav. Suppl. 359, 1960. 4. Effler, D. B . : Defects of the Mitral Valve: Current Concepts of Surgical Treatment, Cleveland Clin. Quart. 29: 167, 1962. 5. Effler, D. B., and Groves, L. K . : Mitral Valve Beplacement: Clinical Experience With the Ball-Valve Prosthesis, Progr. Cardiovas. Surg. 4 3 : 529, 1963. 6. Ellis, F . H., McGoon, D. C , Brandenburg, R. D., and Kirklin, J . W.: Clinical Experience With Total Mitral Valve Replacement With Prosthetic Valves, J . THORACIC & CARDIOVAS. SURG. 46: 482,

1963.

7. Maurice, P., Acar, J., Rulliere, R., and Lenegre, J . : Traitement part la quinidine de 390 cas de fibrillation auriculaire, Arch. mal. coeur 49: 615, 1956. 8. Starr, A., and Edwards, M. L . : Mitral Replacement: The Shielded Ball Valve Prosthesis, J.

THORACIC & CARDIOVAS. SURG. 42:

673,

1961.

9. Starr, A., and Edwards, M. L . : Mitral Replacement: Clinical Experience With a BallValve Prosthesis, Ann. Surg. 154: 726, 1961. 10. Starr, A., Edwards, M. L., and Griswold, H . : Mitral Replacement: Late Results With a Ball-Valve Prosthesis, Progr. Cardiovas. Dis. 5: 298, 1962.