Cardiac surgery and pregnancy

CURRENT

DEVELOPMENTS

An evaluation

Cardiac surgery and pregnancy K.

UELAND,

Portland,

M.D.*

Oregon

THE P UR P 0 s E of this paper is to review current techniques and results of cardiac surgery with a view of evaluating the place of these procedures in the management of pregnancy in women with heart disease. The objective of such management should be to increase the safety and success of pregnancy and the subsequent health of both mother and child.

associated with pregnancy and Berger and HaeneP reported a rate of 0.12 per cent (Table I). Rheumatic heart disease accounts for the majority of the organic lesions, reaching between 78 and 95 per cent in this country and Canada (Table I). Congenital cardiac defects appear to be more common in German and Scandinavian experience, with an incidence of 9 to 44 per cent (Table I). Congenital cardiac defects. The incidence of congenital heart disease in newborns ranges between 1 and 2 per 1,000 births. In infants born to women with congenital heart disease there is approximately a tenfold increase. Neil1 and Swanson,‘ov in 1961, reviewed 508 pregnancies in which one parent had congenital heart disease. Of these infants, 1.8 per cent were born with congenital cardiac defects. The authors considered this to be six times the ‘normal” incidence. Furthermore, there was a high rate of spontaneous abortion in the cyanotic mothers, as high as 80 per cent if the mother’s hematocrit was 65 or more, and 60 per cent in the mildly cyanotic group. The live-born babies were small, their mean birth weight being approximately 5f/2 pounds, compared to 7 pounds, 6 ounces for the children born to fathers with cyanotic heart disease. This raises the possibility that the fetus of a cyanotic mother suffers both genetic and en-

incidence

Heart diseasein pregnancy. In this country the recorded incidence of heart disease in pregnancy in several large series varies from 1.2 to 3.7 per cent (Table I). In Scandinavia it appears to be significantly lower. Buemann and Kragelund,16 in 1962, found an incidence of 0.9 per cent in over 22,000 pregnancies. Their review of the Scandinavian literature showed a rate of 0.23 to 1.1 per cent. Similarly, from Germany, Graeff, Jung, and Sto11,57 in 1963, reported a 0.4 per cent incidence of cardiac disease From the Heart Research Laboratory, University of Oregon Medical School. This investigation was supported in part by Public Health Service Training Grant No. 5Tl-HE5499 from the National Heart Institute. *Present address: Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, Washington.

148

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Cardiac

vironmental hazards in utero. Barnes,s in discussion of Cannel1 and Vernon’s report, refers to the incidence of cardiac anomalies in children whose parents had congenital cardiac lesions as being four to six times the normal rate. In the mother with a congenital anomaly producing cyanosis, the severity of the disorder was again reflected by the hematocrit. When the hematocrit was above 60 only one premature infant survived from a group of 12 pregnancies. On the other hand, when the hematocrit was less than 48, 20 infants survived of a total of 26 pregnancies. Virtually all the infants born to mothers with cyanosis weighed less than the normal mean without regard to the duration of the pregnancy. A similar high incidence of fetal loss was recorded by Copeland and co-worker? if the maternal heart disease caused ryanosis or was associated with pulmonary hypertension. Buemann and in 1962, reviewed 202 cases of Kragelund,17

Table I. Incidence

of heart

surgery

and

pregnancy

infants born to patients with all types of organic heart disease. They found a 25 per cent prematurity rate in mothers with acquired heart disease. The tendency to bear premature infants was increased with the degree of decompensation which occurred during pregnancy, reaching 60 per cent in patients deteriorating from Grade 1 to Grade 4. The over-all perinatal mortality was 8 per cent, the rate being only 3 per cent in mothers with congenital heart disease cornpared to 12 per cent in those with acquired heart disease. Part of this difference the alithors attributed to the increased number of premature and mature stillborn infants born to patients with acquired heart disease. Fetal and maternal mortality. In Mendelson’s experience 98 heart disease was found t,o be the leading cause of maternal death. TXfficulty arises, however, in evaluating the exact mortality rate associated with heart disease because it is not included in the offic+al

disease and pregnancy

in the United

States and Canada

Author lJn.ited

and

year

States

Stander and Kuderlzs (1937) Gorenberg and McClearyss (1941) Stromme and Kuderls* ( 1946) Hamilton61 ( 1947 ) VanderVeer and Ku0139 ( 1950) Fitzgerald4s ( 195 1) Burwell and Metcalfel* (1958) Mendelson”s ( 1960) Canada Cannel1

and

Scandinavia Buemann Bjerring Bergban Hansen Crona MalmnIs (1954) Golden Strand Germany Berger Graeff, *Seen

Vernon?’

and Kragelungls (1925) and SjGstedt and Lachman ( 1954) and Nordstrbm

(1963)

( 1962) (1954) (1954)

( 1955 ) ( 1955)

and Haenel7 (1963) Jung, and StolP (1963) in 258 patients.

149

14,157 28,750

2.9 1.2

23,858 78,530 26,628 55,938 15,434 99,478

3.0 1.7 1.5 1.3 2.3 3.7

Not

312*

0.48 giwn

80+ 95

4.3 5.2 4.4 0.9 14 3

91.2 93 80 92.6 84 93

19

ia

22,293 9.800 29jlOl 37,569 6,900 56,652 60,000

0.9 1.1 0.6 0.6 0.9 0.36 0.23

44 Not available

48 60+

9.3 36 9 22.6

83.4 38 71 58

10,324 30,482

0.4 0.28

28 14.9

59 78

22,474 14,962

0.12 0.4

Not

19 available

60 Not available

Not

available

May

1.50 Ueland

maternal mortality statistics. Eastman and “It is not classified by the Hellman write National Office’ of Vital Statistics as maternal death because the pregnant state was not a direct cause of death but acts through intermediary pre-existing heart disease.” In the maternal mortality statistics from Chicago between 1956 and 1960TB 131 deaths were considered as obstetric. The leading causes of death were listed in order of decreasing frequency as hemorrhage, toxemia, infection, and heart disease. Similarly, in the Minnesota Maternal Mortality Study between 1950 and 195g6 there were 493 maternal deaths, heart disease again being the fourth leading cause. Cardiac disease is certainly responsible for the greatest number of “indirect” or nonobstetric deaths. It appears to be becoming more prominent because of the reduction in deaths from hemorrhage, infection, and toxemia.64. I15 The severity of the heart disease appears to be the most important clinical guide to prognosis. Table II presents the maternal mortality associated with the functional classifications established by the New York Heart Association. In the asymptomatic patient with heart disease the mortality is only twice the over-all incidence in this country reported for 1958 (2.6 deaths per 10,000 live births) .36 On the other hand, in symptomatic and severely ill pregnant cardiac patients there is over a one hundred fold increase in the maternal death rate. History

of cardiac

1, 1!Jb.5

Am. J. Obst. & Gynr~r

surgery

The first surgical attempt at the correction of a heart lesion in the human was probably performed by Tuffier13* in 1913, when he attempted to alleviate aortic stenosis by invaginating the aortic wall with his fingertip. Prior experimental work had been done on dog heart valves in this country in 1906 by MacCallum and McClure.90 In 1923, Cutler and Levine2” performed the first operation for the relief of rheumatic mitral stenosis. They used a transventricular approach passing a knife through the wall of the left ventricle. The patient survived but a large amount of regurgitation was pro-

duced and the technique was abandoned in favor of a transatrial route. In 1925, Souttarlz5 successfully “dilated” a stenosed mitral valve with an index finger inserted through the left auricular appendage. This was the technique that was adopted when operations for mitral stenosis were resumed in the 1940’s. Bailey2 performed a successful mitral commissurotomy in 1948. That same year Brock, Baker, and CampbelP5 used digital pressure to accomplish commissural separation and, in 1950, he reported 6 successfully treated cases. As experience was accumulated it became apparent that adequate commissurotomy could not be accomplished in many patients by digital fracture alone. Valvulotomes and dilators of various types were developed and used. The surgical techniques were modified and refined by many authorities 9, 10, 47, 103, 112, 120 Several large centersspa 73, lo53 Ilo have now adopted the open technique for mitral commissurotomy either routinely or in selected cases. This operation aims at complete opening of the valve and a restoration of functional to nearly normal flow capacity. It is felt that this will prevent re-stenosis which is now being recognized as occurring at an alarmingly high rate. Other advantages of the open technique are the reduction in the incidence of fatal emboli and the abihty of the surgeon to simultaneously correct associated or surgically created mitral regurgitation. Operative correction of mitral insufficiency evolved more slowly, most likely because of the prohibitive mortality rate which was associated with initial attempts at correction, and with the technically more difficult problems of reconstructing deformed valves. Since the advent of open-heart surgery in 1957, however, several technically acceptable procedures have been developed. Mitral valve reconstruction has been performed by some surgeons with encouraging results7’~ 7fi, In. I32 For severely damaged valves several authorities have recently used the technique of total mitral valve replacement. The StarrEdwards ball valve is the most satisfactory prosthesis developed to date. The first successful mitral valve replacement with this

Cardiac

rigid ball valve was performed in September, 1960. Since that time numerous reports of its use have appeared in the literature.38, 43, 46, 33, 104, 127, 129 Ellis and co-workers,42 in 1963, discussed two types of valvular prostheses, the Starr-Edwards ball valve and a flexible monocusp valve. They found no difference in operative or late mortality between the two types of prosthetic valves in a limited number of cases. At this time (February, 1964) the Starr-Edwards valve is most commonly employedzO in cases where total mitral valve replacement is mandatory. The ideal valve has not yet been found. The leaflet valves tend to stiffen and wear out with use probably secondary to the deposition of fibrin, The Starr-Edwards valve has demonstrated its usefulness but its insertion results in hemodynamically significant stenosis as shown by Morrow and Braunwald.lo” These authors reviewed the development of mitral valve prostheses up to 1963.12 Surgical techniques for the correction of acquired aortic valve disease were extensively reviewed by McGoon,g5 in 1963. He distinguished two principal types of acquired aortic valve disease: calcific aortic stenosis and aortic insufficiency. The varied surgical techniques applied to both lesions were critically appraised and their complications discussed. In summing up the state of knowledge, he said, “It is apparent that techniques for the relief of acquired aortic valve disease are new and results are not definite. It is clear that dehiscence of prosthetic valves, bacterial infection in such valves, embolization, and even breakdown of the substance of the valve are hazards which have already been experienced clinically by most pioneers in this field.“ He further stated, “Whenever possible, therefore, surgical treatment should he deferred until more reliable methods can be selected.” McGoon felt that the two preferred methods for correction of aortic stenosis at that time were: ( 1) debridement and (2) excision and prosthetic replacement of one or possibly two of the diseased cusps. For primary aortic incompetence the treatment of choice depended upon the valvular disease. For simple dilatation of the aortic

surgery

and

pregnancy

1.51

root he preferred conversion of the tricuspid aortic valve into a bicuspid valve. If destruction of cusp substance was extensive, patching or prosthetic cusps were recommended as the methods of choice. Since February, 1963, this approach has been altered because of his discovery of a 20 per cent late failure rate folIowing the utilization of Teflon ~usps.~‘~ Starr-Edwards valves are now exclusively employed when prosthetic replacement is necessary and debridement of calcified valves is seldom performed. In 1952 Hufnagel, Villegas, and Nah&” clinically employed for the first time a ball valve prosthesis in the descending aorta of a patient with aortic insufficiency. This valve has now been supplanted by a modification of the Starr-Edwards mitral valve.‘2”. “” Scvera1 authorities have employed this prosthetic aortic valve with increasing success.“‘. ‘!I. 40, 02, 96, 1(17, 108.122Experience with ]eafjyt replacement of the aortic valve has heen accumulated by others in the past.‘, “I. ‘-‘. 74. Q7!lZ1 Opinion is divided, the ideal technique and prosthesis has yet to be discoverrd. and long-term results are not available for rvaluation. Again problems following operation have been encountered. The cusps ultimately become thickened by fibrin and protein deposition, and tissue ingrowth with resultant decrease mobility, stiffening. and treat ion of a pressure gradient across the aortic orifice. Late failures due to dehiscence of yuture lines? fracture of the cloth substance of the endocarditis have: also CUSP,and bacterial been noted.*, s3, 85 Bristow and co-w-orkers’” in 1963 demonstrated gratifying lrrmodynamic results with the aortic valve rrplacement. However, a small but significant transvalvular pressure gradient was observed along with abnormalities in left ventricuIar function with exercise. Late complications have consisted of emboli and dehiscence of cutlu-e lines. Prosthetic valvular replacements and i/or valvular reconstruction procedures art: now being performed with increasing frequency. The mortality rate is high, ranging from 10 to 30 per cent depending on such factors as the type of procedure used, the tape of

152

Ueland

May 1: 1963 Am. J. Obst. & Gynec.

lesion encountered, and the condition of the patient. For multivalvular surgery, this rate is doubled.22xIS1 Again, as experience has been accrued, the mortality and the complication rates have declined.‘“, 38, 39, 40, 42, 71, 72, 74, 75, 83, 95, 96, 97, 108, 111,

121,

1221 l”l I30313’ The majority of patients operated upon, especially for prosthetic replacement, have been gravely ill. The immediate postoperative resultshave been very encouraging, most authorities reporting good results in 70 per cent of those patients who survive surgery. But follow-up is limited to 1 to 2 years. The entire field of prosthetic valvular surgery is in a state of flux and it is difficult to summarize or express current trends. Cooley and co11eaguePfeel that the Starr-Edwards prosthesishas opened a promising field for treatment of acquired valve disease. They believe it provides an effective means of valve substitution which is currently replacing all other techniques for surgery of deformed valves. Before development of extracorporeal circulation surgery for congenital defects was limited to the less complex lesions such as pure pulmonary stenosisand atria1 septal defects because these could safely be repaired under hypothermia alone. Several large series have recently been reported in which cardiac surgery was performed in children for a variety of congenital cardiac defects. The over-all operative mortality has steadily improved. In Gross’ series,59in 1959, in approximately 200 casesthe mortality rate was 22 per cent. In the series of 679 casesreported in 1963 by Riker”’ and Smith,lZ3 the Table II.

Maternal mortality

Strommeand Hamilton61

and

KudeG* (1947)

Vander Veer and Ku0139 Friedberg4* ( 1956) Burwell and Metcalf+ Mendelsonsg ( 196 1) Sutherland and Bruce’35

Functional

Classes

( 1946)

( 1950)

( 1958) I 1962 1

549 1.335 (Total classifications) 349 337 226 3,263 448

I and Total

Total No. of cases

year

Improved diagnostic and surgical skills now allow many infants with severe cardiac defects to survive the first year of life. Cooley, Berman, and Santibanez-Woolrich,” in 1962, reported on 400 consecutive operations in newborn infants with varied congenital defects with a 72 per cent survival rate. The decision to operate in each case was based on the clinical impression that survival was not possiblewithout surgery. In the same report, they studied 154 necropsies of infants whose deaths were attributed to cardiovascular malformations. Among these, 70 could have had palliative or corrective surgery and 50 could, therefore, have been salvaged in the opinion of the authors. This figure becomessignificant when we consider that in 1959 alone 7,523 infants died of congenital cardiovascular diseaseduring the first year of life.133 Cooley, Berman, and Santibanez-WoolrichZ4 emphasize, as do Mauck and co-workersg3and McGeorge and Roddag4 that vigorous, precise dia,gnostic investigation, including selective angiocardiography, should be undertaken as soon as a strong clinical suspicion of congenital heart disease exists. Immediate surgery is fre-

according to cardiac functional classification

I Author

over-all mortality had declined to 15 per cent. This rate is reduced even further if statistics are compiled from just the past 2 years, and if the patients are limited to children up to the age of 14. The trend and scope of cardiac surgery for congenital cardiac defects are indicated by the fact that over 500 operations for complete repair of the tetralogy of Fallot alone appeared in the literature in 1963.41,49300,05,91% 117,123

No. all

2 Not given 3 1 0 7 1

II

lFunctiona1

deaths 1

Classes Total

%

Total No. I of cases I

No.

0.4 2

88 -

6 Not given

0.9 0.3 0.2 0.2

2:: 72 427 52

11 24 3 24 6

III

and deaths /

% 6.8 18 18.7 11.5 4.2 6 11.5

IV

Volume Number

92 1

Cardiac

quently needed and many of these lesions are now correctable. MitchePO’ reviewed the courses of patients with congenital heart defects in 143 general hospitals in the United States in 1963. He found a 1.2 per cent mortality rate in 751 cases undergoing diagnostic procedures. At the same time he quoted an operative mortality of 12 per cent (for all age groups) and compared this to 15.4 per cent in those patients treated medically. Lewis,81 in early 1963, expressed some trends and thoughts. “The work of the year [ 19621 in cardiovascular surgery displayed in numerous papers, shows in general a kind of developing maturity. There is not as much excitement as in some earlier years. Time has been found for some carefully detailed studies of rather insignificant matters. But there has been time, too, for needed appraisal, and time to learn more about all the complex pathologic physiology encountered. And there has been time and genius enough, fortunately, to make some very valuable observations and discoveries.“* Cardiac

surgery

in pregnancy

Varied opinion exists regarding the exact role of cardiac surgery during pregnancy. It appears now to have a definite but limited place alongside the accepted medical management in the over-all care of the patient. The earliest reports of cardiac surgery performed in pregnancy appeared in 1952. Brock,l* Cooley and Chapmanz5 Logan and Turner,kG and Mason!‘2 reported on a total of 11 patients who underwent mitral valvotomy during pregnancy with one maternal death and one premature delivery. The following year Dogliotti3” performed a successful commissurotomy in Italy, and Burwell and KamseylQ described 7 additional patients who underwent mitral valvotomy of which 5 were successful. During the next several years larger groups of patients were studied and reported by many investigators. By 1961, Harken and Taylor ” had collected 394 cases “From Lewis, vascular surgery, permission.

F. J.: What’s new in surgery: Surg. Gynec. & Obst. 116: 131,

Cardio1963, by

surgery

and

pregnancy

153

from the literature with a total of 7 maternal deaths (1.8 per cent) and 35 fetal deaths (9 per cent) . Since that time more than 12t) additional cases have been described’. ‘. .‘!I, 52, 70, ~0, lo61 1z4 with only 2 maternal deaths (1.7 per cent) and a fetal loss of 9 (7.5 per cent). The surgery was usually performed in Class 3 and 4 cardiac patients. When we compare the occurrence of fetal and maternal deaths with those in patients with similar functional classification treated medically, the above results are impressive. T’:ible II shows a maternal mortality of 4.2 \D 18.7 per cent in cardiac patients of Clasq III and Class IV treated medically, and a ietal mortality of up to 50 per cent has been (1~ SCribed4Y, 5i, 61, ~j!).I’*(, in this group of patients. However, the optimistic surgical statistics are difficult to understand because. the mortality rates associated with mitral val\.otomy in nonpregnant patients range from 4 to 11 per cent in several recent largt: series.‘. N. ‘l’, 6x, 88 The discrepancy may, irowever, be partly accounted for by the agtt clifference of the patients in the two group’ and the fact that in general, cardiac surgery during pregnancy has been done more recently and therefore reflects more experience. improved diagnostic and surgical skill. and the increased use of open heart surgery i:~ selected patients. GilchrisP clearly drxnonstrated the influence of age on survival after mitral valvotomy. Of 109 patients, z:eq 0 to “9, only one death was recorded (less than 1 per cent). but in the 293 parients aged 30 or more? 15 deaths occurred ! 5.1 per cent‘) . Similarly, the preoprrati\,t. Wertional tolerance greatly influenced survival, which was 1.2 per cent for Classes 1 and 2, and 5 to 20 per cent for Classes :i and 4. respectively. Lowther and Turner? in 1963, analyzed 500 patients treated bv vnl~c~to~ny for proved severe mitral stenosis and listed four categories where operative risk was considerably increased : those patients with ( 1’: atria1 fibrillation : (2) considerabk~ cardiac enlargement; (3) age 50 or rnorc: and (4) heavy calcification of the valve. Starr and McCord recently reviewed 200 consecutive cases of mitral valve surgery nerfonned

154

Ueland

Table III. (January,

Mitral valve surgery at The 1960, through December, 1963) Total

Type Closed

of

procedure

Mitral

and

aortic

No.

of cases

valvotomy

Open plastic reconstruction Plastic reconstruction with replacement Mitral replacement

University

aortic

replacement

No. of deaths

of Oregon

Mortality (%I

106

2

18 7

2 1

11 14

54

11

21

17

5

31

at the University of Oregon Hospital since 1960. Of these, 106 were closed valvotomies which resulted in 2 operative deaths (1.9 per cent). This mortality rate is the same as that encountered in reported patients similarly treated during pregnancy. Table III shows the type of procedure used and the corresponding operative mortality for the entire series. It presents, as well, the varied techniques presently available to the cardiac surgeon who only recently has enjoyed such a selection. Mitral commissurotomy. Although markedly improved, mitral commissurotomy is still associated with a significant operative mortality, and it is also accompanied by a very definite rate of patient deterioration following initial improvement. Logan, Lowther, and Turners5 studied 264 survivors of mitral valvotomy and found a 5 per cent incidence of restenosis in 5 years and 60 per cent in 9 years. Morse, Hirose, and Baileylo are more encouraging as they compare a 5.4 per cent rate of restenosis before 1954 with one of less than 1 per cent for 1955. They attribute the decline to refined and perfected surgical techniques and feel that the results will further improve with open-heart surgery in all patients with mitral stenosis. Many others have shown a significant incidence of deterioration after successful miThe in&tral valvotomy 3, 44, 58, 76. 84, 87, 88 dence of restenosis is difficult to interpret because of the many variables encountered,44 but since it has been shown to occur in a significant number of cases it must always be kept in mind. The average interval be-

Hospital

1.9

Comments Three required emergency valve replacement because of torn leaflets

Five late infection

deaths

early

in series

from

tween initial and repeat surgery following restenosis has been shown to be 4 to 7 years.89a lo57 lZo The dangers of reoperation are increased and the results are less satisfactory than those obtained with the primary surgical attempt. Many authors feel that mitral valvotomy is a palliative rather than a corrective procedure.43’ 521 136 Szekely and SnaithlZ6 said, “Mitral valvotomy is to be regarded as a therapeutic episode in the course of rheumatic heart disease. At best, the patients are greatly improved and are returned to a previous and more favorable stage of the disease. Progression of the cardiac condition at a rate peculiar to each patient continues in the majority of cases.“” The benefits of vulvotomy are often of limited duration. Any surgery should, therefore, be timed for maximum effectiveness and, ideally, be performed under basal conditions which do not prevail during pregnancy. Gentilli and Gili 5o believe that the indications for surgery are the same in the pregnant as in the nonpregnant patient. They favor surgical correction of mitral stenosis even in milder cases to prevent development of decompensation later. Dogliotti and associates32 agree essentially and emphasize that pregnancy does not increase the risks, difficulties, or complications of mitral commissurotomy. This plea for surgery in the early stages of mitral stenosis must be weighed against the hazards of earlier restenosis and the need for earlier reoperation. *From Szekely, P., and Snaith, L.: The place of cardiac surgery in the management of the pregnant woman with heart disease, J. Obst. & Gynaec. Brit. Comm. 70: 69, 1963.

Volume Number

Cardiac

92 1

The opinion that pregnancy does not alter the surgical mortality or morbidity is also shared by many others,S1l 63167, 7oy“3 13’ but these authors all feel that nonoperative management is preferred. Harken and Taylor63 summarize the current majority opinion : “In principle, physicians and surgeons alike wouId prefer to avoid any and all intrapartum operations. Surgery should be undertaken only when it is clear that the result desired can be best attained by an operation and the risks are acceptable.” They continue, “Decisions regarding medical management or surgical intervention must be based on a thorough knowledge of the risks of surgery, the safety of continuing the pregnancy in conjunction with really complete medical treatment.“* In other words, each patient should be carefully evaluated by surgeon, internist, and obstetrician and a complete plan for total management established. Lee criteria and Pates6 set down the following for operative intervention in pregnant patients with mitral stenosis: “ ( 1) those with progressive cardiac disability during the first or second trimester with proven mitral stenosis, but without mitral insuficiency or aortic valve disease, (2) any pregnant patient with dominant mitral stenosis (surgically remediablej who cannot be carried through pregnancy by medical management (for examp!e, those who are refractory or those who have recurrent heart failure or severe, protracted hemoptysis) , (3) patients who become pregnant when they have mitral stenosis with a functional cIassification of III or IV, and (4) Class II patients with mitral stenosis who have progressed to Class III during previous pregnancies but who have ‘weathered it through’ with medical management.“? These authors feel that the optimal time for operation is between the eighteenth and twenty-eighth weeks. Metcalfe and UelandlO’ believe that the decision for surgery should, “From Harken, D. E., and Taylor, W. J.: Cardiac SW-gery during pregnancy. Clin. Obst. & Gynec. 4: 697. 1961, published by Hoeber Medical Division, Harper & Row, Publishers. Incol-plated. iFrom Lee, aspects of heart 1953.

W. H., d&are

Jr., and Pate, J. W.: Surgical in pregnancy, GP 28: 78, Nov.:

surgery

and

pregnancy

155

be made before the whenever possible, twentieth week of pregnancy and that operative intervention in general is to be avoided after the twenty-fourth week of pregnancy. This opinion is based on the fact that the maximum cardiovascular burden experienced in pregnancy occurs between the twentyeighth and thirty-second weeks of gestation. We think, too, that in any patient undergoing surgery for mitral stenosis, an open heart approach may be needed for maximum benefit. To date the reported hazards of total cardiac bypass (discussed in detail below 1 to the fetus are alarming. This means to us that, whenever possible, mitral valve surqet-y should be carried out before or after pregnancy rather than risk a second-best surgical result, on the one hand, or fetal deat?, or deformity on the other. In general, present practice has limited the number of patients selected for operation now compared to the past. It is only by judicious selection of patients for vahotomy that we can arrive at the ultimate goal which is to decrease maternal mortality. Recent statistics favor a combined medical and surgical approach. O’Driscoll, Barry. and Drury113 had one maternal death jO.34 per cent) in 289 pregnant patients with ileart disease, mitral valve surgery being successfully accomplished three times. Gilchrist’s series”? of 592 cardiac cases from 1953 through 1960 revealed only 5 mate-ma1 deaths (0.8 per cent). Mitral valvotomy was performed in this series 11 times. Although much information has now been gathered about mitral valvotomy in l)reynancy, little experience has been accumulated regarding other types of cardiovascular surgery in the pregnant state. Pulmona,ry stenosis, atria1 septal defect, coarctation of the aorta, and patent ductus arteriosus ;rre among the cardiac lesions corrected su(‘cessfully during pregnancy.4. 14. 16. 21. 63, 71. !)Y.li.6. 11’, 13{’ Most reports relate only a. singltx experience. According to Harken and TaylorG” these conditions in nonpregnant patients cm now be corrected by appropriate techniques with a mortality of less than 5 per cent Repair of congenital defects. It has been

156

Ueland

shown that women with congenital heart disease may sustain multiple pregnancies without incident2*p 27~142 The favorable maternal prognosis and fetal survival suggest that congenital heart disease per se is not a sufficient indication for cardiac surgery in the gravid state. With rare exception, therefore, the surgical correction of congenital heart defects should be deferred until after delivery. Copeland and co-workersZ7 in 372 pregnancies in women with congenital cardiac defects recorded one maternal death (less than 0.3 per cent), this being due to staphylococcal bacterial endocarditis complicating a dental extraction at 3 months’ gestation. The perinatal mortality was not increased above that seen in normal patients. Pregnancy and coarctation of the aorta was recently reviewed by Goodwin.54 He recorded a total of 150 patients with 380 pregnancies in which there were 13 maternal deaths (3.5 per cent). There was little evidence suggesting that the stress of pregnancy predisposed to aortic dissection, rupture, or to cerebral vascular accidents. However, he deemed it important to evaluate the patient carefully for possible * associated disease. Eight of the 13 recorded deaths occurred in patients who had accompanying cardiac defects. He quoted an operative mortality of 8.6 per cent in 1,600 patients who underwent resection of the coarctation in the nonpregnant state and recommended that the uncomplicated case of coarctation should be repaired in the postpartum period. Burwell and Metcalfe18 agree because of their feeling that vascular changes occur during pregnancy which may interfere with adequate correction. A rare anomaly associated with by Penman and pregnancy was recorded in 1963. Their patient underwent Whitty,l14 3 pregnancies resulting in 2 surviving children and 1 premature infant who died. The mother had a three-chambered heart with dilated normal atria and a small rudimentary chamber with a pocketlike cleft opening only to a huge main ventricular cavity. This unusual and extreme case exemplifies and emphasizes the fact that in most forms of congenital heart disease pregnancy is re-

May 1, 1965 Am. J. Obst. & Gyncc.

markably safe and well tolerated by patients under strict medical management. Early in 1956, Rowbotham and coworkersus used hypothermia in pregnancy for the first time. The patient had suffered severe head trauma at 8 weeks’ gestation. One week of therapeutic hypothermia was used to maintain body temperature at 30 to 34’ C. She was delivered of a normal infant at term. Later that same year, Daley, Harrison, and McMillan30 combined hypothermia with 3 minutes of circulatory arrest to perform a pulmonary valvotomy under direct vision. Again a successful termination of pregnancy was attained.

Open heart surgery-use of extracorporeal circulation. In July of 1958, Leyse and coworkers** first used extracorporeal circulation during open-heart surgery for congenital aortic stenosis in a patient at the eighteenth week of gestation. The postoperative course was uneventful and the patient delivered near term, but the infant had multiple congenital anomalies and subsequently died at 4 months of age. In 1959, Dubourg and associates33 performed a pulmonary commissurotomy and repaired an atria1 septal defect at 3 months’ gestation using extracorporeal circulation. The postoperative course was benign but the patient had a spontaneous abortion 3 months later. No mention is made of congenital anomalies in the fetus. In 1963, Kay and SmithTo described two open-heart procedures in Class 4 cardiac patients-one with a ventricular septal defect, the other with anomalous pulmonary venous drainage. Both infants and one mother died. Lee and Pates0 refer to a 25 minute perfusion in a patient 5 months pregnant for the repair of a leaking traumatic aneurysm of the aortic arch. The mother and child survived surgery and she was delivered normally 3 months later. As can be ascertained, experience is extremely limited with open-heart surgery during pregnancy. Maternal and especially fetal mortality and morbidity appear high. Recent communications (February, 1964) revealed that more experience has been accumulated at several large centers.ll> 23, 37 Both open-heart procedures and cardiopulmonary

Volume Number

92 1

Cardiac

surgery

and

pregnancy

157

Table IV. Open heart surgery in pregnancy Author

Year

Kirklin and workers77

wall

tech-

1957

1 Congenital pulmonary stenosis

No-hypothermia and 3 minute circulatory arrest

1958

1 Congenital stenosis

Yes-20

1959

1 Congenital pulmonary stenosis and aortic septal defect

Yes

1963

1 Leaking aneurysm arch

Yes-45

1963

1 Ventricular septal defect 1 Anamolous pulmonary venous drainage

Not

Braunwoldll

1964

3 Aortic feet

septal

Yes-duration stated

Cooleye

1964

1 Aortic

stenosis

Leyse and worker+

co-

Dubourg and workers33

Lee and

Kay

and

co-

Pates0

Smithrs

de-

No-atria1 nique

1. Aortic feet

Harrison, McMillansa

septal

Length of gestation

Extracorporeal circulation

1956

Daley, and

co-

No. and type of lesion corrected

aortic

traumatic of aortic

de-

Yes-l

1 Ventral septal defeet with tricuspid insufficiency 1 Ventricular defect

septal

-

bypass have been used with reduction in both fetal and maternal complications. The number of cases, however, are too few to draw any adequate conclusions (Table IV).

Trends in cardiac surgery.

Current

trends

in cardiac surgery favor the use of open techniques and extracorporeal circulation. The results obtained are progressively improving and as experience is gained with

minutes

minutes

stated

not

Not

stated

Results and comments Normal

infant

at term

3 Months

Normal

infant

at term

4 Months

Uneventful pregnancy. Infant died at 4 months, had multiple congenital anomalies

3 Months

Spontaneous at 6 months

5 Months

Normal term

Not

stated

One maternal and 2 fetal

All

in first trimester

All

infant

abortion

at

death deaths

delivered normal fants at term. Pregnancy unknown at time of surgery

7 minutes

2 Months

Spontaneous abortion 10 days after operation. Preoperative threatened abortion

7 minutes

3 Months

Normal term

3 Months

Normal infant al. term. Patient died IO days postpartum from uncontrollable paroxysmal tachycardia --_. _. --

16%

minutes

infant

at

reference to both perfusion and surgical techniques the morbidity and mortality will further decline. The pregnant patient ran perhaps tolerate the open procedure as well as the nonpregnant, but the fetus may not. Pump oxygenator perfusion may be as safe in the pregnant as in the nonpregnant patient. However, with extracorporeal circulation, sludging and stasis of blood in the

158

Ueland

placental sinuses may occur, with resultant fetal hypoxia and congenital malformation. The exact effects on the fetus are unknown but they are probably similar to those of an episode of severe maternal hypoxia. Because of the uncertainty of the results, it would be best to assume that significant fetal hypoxia is a possible complication of total cardiac bypass and to delay open-heart surgery with pump oxygenation during pregnancy except for those cases in which the patient would probably not live without surgical intervention. Pregnancy

following

cardiac

surgery

Numerous reports have appeared of pregnancies following corrective cardiac surgery for acquired valvular disease, specifically mitral stenosis (Table V) . As can be seen over 400 pregnancies are recorded with only one maternal death. Mortensen and Ellsworth’06 revealed a 65 per cent complication rate and a 76 per cent success rate (living infant) in 96 women with 291 pregnancies before valvotomy and compared these results with a 20 per cent complication rate and an 89 per cent success rate in 30 women with 65 pregnancies after valvotomy. Szekely and 15 women who had had Snaith136 studied 22 pregnancies before surgery with a 60 per cent incidence of heart failure, and 16 pregnancies after valvotomy with only 25 per cent experiencing heart failure. Similarly, Gilchrist5’ followed 28 patients through pregnancy pre- and postoperatively. Twenty-three of the 28 were considerably disabled before valve surgery, whereas only 8 were so classified postoperatively. Thus, the complication

Table V. Pregnancy

following

Author

mitral

valvotomy

I

Year

MendelsonQs Reid, Berger, and Stevenson116 Harken and Taylor63 Gillersons3 Gilchrist Mortensen and Ellsworthlos Szekely and Snaithlss Total *Thirty-four

already

included

No. of Pregnancies

1960 1960 1961 1962 1963 1963 1963 in Mend&on’s

statistics

rate of the surgically treated pregnant cardiac is reduced by one-half to two-thirds that of the unoperated patient with symptomatic rheumatic mitral stenosis. Careful family planning is indicated in women who have undergone corrective surgery for mitral stenosis because of the limited duration of the surgical benefits from this procedure. Pregnancy should be undertaken at the time when the patient is experiencing maximum benefits from her surgery and should not be unduly delayed. Pregnancy in patients with surgically corrected congenital cardiac lesions are now being encountered more frequently. Mendelsong8 reported on 51 pregnancies following corrective surgery for coarctation of the aorta with no maternal deaths and 10 fetal deaths. Salvaggioln’ recorded 6 successful cases of pregnancy following complete correction of tetralogy of Fallot from the literature and added one patient of his own with 2 uncomplicated pregnancies. Patients who have had successful surgery for correction of a patent ductus arteriosus can undertake pregnancy without an added risk. Harken and Taylor63 summarize the general feeling regarding surgical correction of congenital heart diseases, “Ideally, the management of cardiac disease in women of childbearing age is prevention of conception, surgical correction and subsequent pregnancy.” Experience with pregnancy in patients with a Hufnagel valve is limited to 4 cases reported in the literature.*O, ‘ll 28* 56 All patients successfully completed their pregnancies and were delivered of normal infants at term. The increased cardiovascular burden was

255 2 37, 2 28 65 37 426 above.

Fetal

mortality

15 0 0 0 Not given 7 10 32

Maternal mortality 0 0 0 0 0 0 1 1

Volume Number

92 1

Cardiac

well tolerated in all but one patient who Presently, experienced congestive failure. there are 2 patients being followed in our clinic who have had Starr-Edwards aortic valve prosthetic replacements. One is 5 months’ pregnant, the other is 8 months’ pregnant and both are free of any cardiovascular symptoms. Mortensen and EllsworthloG list the surgically corrected cardiac lesions in patients who have subsequently achieved a normal pregnancy and delivery: rheumatic mitral stenosis and/or insufficiency, atria1 septal defect, ventricular septal defect, patent ductus arteriosus, coarctation of the aorta, anomalous pulmonary venous connections, tetralogy, and arteriovenous commune. Because of improved diagnostic and surgical skills many infants with severe cardiac defects are now able to survive the first years of life and will subsequently enter the childbearing age and come to the care of the obstetrician and cardiologist. Presently, our experience in handling these patients is meager but in future years, due to the steady decline in the incidence of rheumatic heart disease, they will comprise an increasing proportion of our medical concern. Fertility, and

therapeutic

abortion,

sterilization

Serious cardiovascular disease can substantially reduce sexual or ovarian functions. In some patients involuntary sterility results. Mortensen and Ellsworthlo6 demonstrated that it was possible in such cases for patients to improve sufficiently after successful cardiac surgery for normal pregnancy and delivery to occur. Of 18 patients who were involuntarily sterile, and subsequently underwent cardiac surgery for various heart lesions, 12 had babies postoperatively. They all were delivered normally following uneventful pregnancies. Furthermore, the authors feel that sterilization procedures should not be performed on patients with surgically correctable cardiac defects. They studied 62 couples sterilized before the wife’s cardiac surgery. Of these, 38 women (61 per cent) improved sufficiently postoperatively so that pregnancy

surgery

and

pregnancy

159

could have safely been undertaken in the Winter and associates”’ authors’ opinion. and Mendelson”8 agree that sterilization need no longer be considered in patients who ma:, benefit from cardiovascular surgery and new therapeutic agents. In addition, they feei that contraception is preferable to sterilization in almost all instances because it i\ reversible and produces less of a psychological impact. If a surgical method of sterilization is decided upon it should not be per-formed during the early puerperium becallse of the threat of decompensation from an elevated blood volume.3’. 78 Therapeutic abortion appears now to be rarely indicated on the basis of most cardiovascular ciiseaSe.““. 51. iz. 101. 137 It has been of lifesal inq value in some patients in the past but the necessity for its use has diminished. Finally, sterilization should no longer be considered a corollary to therapeutic abortion for th17 reasons already stated--that the exist ine heart lesion may be amenable to surgrlry. Successful operation may make future rhiltlbearing possible. Summary

and

conclusions

Approximately one pregnant patient in 80 has heart disease. Improved medical .tnd surgical management has reduced the rnaternal mortality rates from toxemia, hemorrhage, and infection. Although maternal deaths from heart disease have declined, this group now comprises one of the major causes of maternal mortality. Most authorities feel that careful and strict medical management is preferred for the pregnant cardiac patient. surgery being reserved for the few patients with mitral stenosis who show progressive disability early in pregnancy and for those with refractory failure or severe hemoptysis. Eastman,35 in agreeing with Gilchrist, writes! “The most important factor in the reduction of maternal mortality in the past 30 years is the employment of prolonged bedrest in the hospital. Indeed, by and large, the hest management of desperate heart disease in pregnancy is not therapeutic abortion or valvotomy but hospitalization throughout pregnancy, usually with complete bedrest.

160

1May 1, 196.5 Am. J. Obst. & Gynrc.

Ueland

But valvotomy in pregnancy does have a place, it seems to me, even if a small place. This is in the patient who decompensates early in pregnancy and in whom bedrest and the other usual measures do not completely restore compensation within a fortnight or so.“* The question is not whether cardiac surgery can or cannot be performed during pregnancy but rather when it is indicated in the over-all management of the pregnant patient with heart disease. With increasing experience and perfection of surgical and technical skill heart surgery will become an increasingly important adjunct to medical management. Future statistics will indicate the safest and best time for cardiac surgery. At present long-term benefits from heart surgery during pregnancy have not been clarified. When the decision for surgery is “From Eastman, N. J.: Gym. Surv. 18: 570, 1963.

Editorial

comment,

Obst.

&

made the best operation for each patient must be performed. Reoperation is difficult and dangerous and the results are generally unsatisfactory. All these principles should be considered and carefully weighed as one assumes the responsibility for the care of the pregnant patient with heart disease and before any active surgical intervention is undertaken. Addendum The 2 patients with prosthetic Starr-Edwards aortic valves subsequently have been delivered of normal infants at term following uncomplicated pregnancies. I would like to express my sincere appreciation to Drs. Albert Starr and Colin McCord for their appraisal of the manuscript and to Dr. James Metcalfe for his enthusiasm, encouragement, and assistance in preparing this manuscript.

REFERENCES

1. Angelino, P. F., Lo Bue, B., Tartara, D., and Garbagni, G.: Panminerva Med. 4: 211, 1962. 2. Bailey, C. P.: Dis. Chest 15: 377, 1949. 3. Baker, C., and Hancock, W. E.: Brit. Heart J. 22: 281, 1960. 4. Baker, J. L., Russell, C. S., Grainger, R. G., Taylor, D. G., Thornton, J. A., and Verel, D.: J. Obst. & Gynaec. Brit. Comm. 70: 154, 1963. 5. Barnes, A. C.: In discussion of Cannell, D. E., and Vernon, C. P.: AM. J. OBS;. & GYNEC. 85: 744. 1963. 6. Barno, A., Freeman, D. W., and Baken, M. P.: Minnesota Med. 45: 847, 1962. 7. Berger, J., and Haenel, L.: Schweiz. med. Wchnschr. 93: 453, 1963. 8. BjGrk, V. O., Cullhed, I., and Lodin, H.: J. Thoracic & Cardiovas. Surg. 45: 635, 1963. 9. Bjijrk, V. O., Holmdahl, M. H:Son, and Lof, B.: J. Thoracic & Cardiovas. Surg. 41: 236, 1961. 10. Bolton, H., and Musser, B. G.: Dis. Chest 32: 247, 1957. 11. Braunwald, N. 6.: Personal communication. N. S., and Morrow, A. G.: 12. Braunwald, Progr. Cardiovas. Dis. 5: 313, 1963. 13. Bristow, J. D., Starr, A., McCord, C. W., Crislip, R. L., and Griswold, H. E.: Circulation 28: 695, 1963. 14. Brock, R. C.: Proc. Roy. Sot. Med. 45: 538, 1952.

15. Brock, R. C., Baker, C., and Campbell, M.: Brit. M. J. 1: 1283, 1950. 16. Buemann, B., and Kragelund, E.: Acta obst. et gynec. scandinav. 41: 57, 1962. 17. Buemann, B., and Kragelund, E.: Acta obst. et gynec. scandinav. 41: 80, 1962. 18. Burwell, C. S., and Metcalfe, J.: Heart Disease and Pregnancy, Physiology and Management, Boston, 1958, Little, Brown & Company. 19. Burwell, C. S., and Ramsey, L. H.: Tr. A. Am. Physicians 66: 303, 1953. 20. Canfield, M. C., Edgar, A. L., and Kimball, A. P.: California Med. 88: 54, 1958. 21. Cannell, D. E., and Vernon, C. P.: AM. J. OBST. & GYNEC. 85: 744, 1963. 22. Cartwright, R. S., Giacobine, J. W., Ratan, R. S., Ford, W. B., and Palich, W. E.: J. Thoracic & Cardiovas. Surg. 45: 35, 1963. 23. Cooley, D. A.: Personal communication. 24. Cooley, D. A., Berman, S., and SantibanezWoolrich, F. A.: J. A. M. A. 182: 912, 1962. 25. Cooley, D. A., and Chapman, D. W.: J. A. M. A. 150: 1113, 1952. 26. Cooley, D. A., Nelson, T. G., Beall, A. Cl., Jr., and Hallman, G. L.: Am. J. Cardiol. 13: 102, 1964. 27. Copeland, W. E., Wooley, C. F., Ryan, I. M.; Runco, V., and Levin, H. S.: A& J. OBST. & GYNEC. 86: 107. 1963. 28. Crockett, J. E., Kittle, C. F., and Dimond, E. G.: Am. Heart J. 57: 144, 1959.

Volume Number

29. 30. 31.

32.

33.

34. 35. 36.

37. 38. 39. 40. 41.

42.

43. 44. 45. 46.

47. 48.

49.

50. 51. 52. 53. 54. 55. 56. 57.

92 1

Cutler, E. C., and Levine, S. A.: Boston M. & Surg. J. 188: 1023, 1923. Daley, R., Harrison, G. K., and McMillan, I. K. R.: Lancet 2: 875, 1957. Davis, M. V.: In discussion of Mulder, D. G., Kattus, A. A., Jr., Fonkalsrud, E. W., and Longmire, W. P.: J. Thoracic & Cardiovas. Surg. 46: 479, 1963. Dogliotti, A. M., Dellepiane, G., Actis Dato, A., Gentilli, R., and Siliquini, P. N.: J. Thoracic & Cardiovas. Surg. 39: 663, 1960. Dubourg, G., Broustet, P., Bricand, H., Fontan, F., Tarieux, M., and Fontanille, P.: Arch. mal. coeur 52: 1389, 1959. Eastman, N. J.: Obst. & Gynec. Surv. 15: 27, 1960. Eastman, N. J.: Obst. & Gynec. Surv. 18: 570, 1963. Eastman, N. J,, and Hellman, L. M.: Williams Obstetrics, ed. 12, New York, 1961, Appleton-Century-Crofts, Inc. Effler, D. B.: Personal communication. Effler, D. B., and Groves, L. K.: Dis. Chest 43: 529, 1963. Effler, D. B., Groves, L. K., and Favaloro, R.: Arch. Surg. 88: 145, 1964. Effler, D. B., Groves, L. K., and Favaloro, R.: Cleveland Clin. Quart. 30: 173, 1963. Ehrenhaft, J. L., Fisher, J. M., and Lawrence, M. S.: J. Thoracic & Cardiovas. Surg. 45: 224, 1963. Ellis, F. H., McGoon, D. C., Brandenburg, R. O., and Kirklin, J. W.: J. Thoracic & Cardiovas. Surg. 46: 482, 1963. Ellis, L. B., and Adler, L. N.: Am. J. Cardiol. 12: 17, 1963. Ellis, L. B., Harken, D. E., and Black, H.: Circulation 19: 803, 1959. Fitzgerald, J. E.: J. A. M. A. 146: 910, 1951. Ford, W. B.: In discussion of Ellis, F. H., Jr., McGoon, D. C., Brandenburg, R. O., and Kirklin, J. W.: J. Thoracic & Cardiovas. Surg. 46: 496, 1963. Fraser, K., and Kerr, I. F.: Brit. M. J. 2: 339, 1961. Friedberg, C. K.: Diseases of the Heart, ed. 2, Philadelphia, 1956, W. B. Saunders Company. Garamella. J. J., Jensen, N. K., Schmidt, W. R., and Lynch, M. F.: Minnesota Med. 46: 234, 1963. Gentilli, R., and Gili, G.: Minerva Cardioangiol. 11: 95, 1963. Gerbie, A. B., and Skom, J. H.: M. Clin. North America 45: 133, 1961. Gilchrist, A. R.: Brit. M. J. 1: 209, 1963. Gillerson, A. B.: Akush Ginek. 38: 93, 1962. Goodwin, J. F.: Clin. Obst. & Gynec. 4: 645, 1961. Gorenberg, H., and McGleary, J.: AM. J. OBST. & GYNEC. 41: 44, 1941. Gorman. 1. F.: Obst. & Gynec. 20: 238, 1962. Graeff, H., Jung, W., and Stall, P.: Med. Welt 1: 45, 1963.

Cardiac

58.

59. 60. 61. 62.

63. 64. 65. 66. 67.

68.

69. 70. 71. 72. 73. 74. 75. 76.

77.

78. 79. 80. 81. 82.

83.

84. 85. 86.

surgery

and

pregnancy

i61

Greenwood, W. F., Aldridge, H. E.. and McKelvey, A. D.: Am. J. Cardiol. 11: 348, 1963. Gross, R. E.: New England J. Med. 1047, 1959. Hallman, G. L., and Cooley, D. A.: J. Thoracic & Cardiovas. Surg. 46: 419, 1967. Hamilton, B. H.: Am. Heart. J. 33: ti63, 1947. Harken, D. E.: In discussion of Mulcier, D. G.. Kattus. A. A.. Tr.. Fonkalsrud. E:. M’.. and Longmire, W. P.: J. Thoracir & i :ardiovas. Surg. 46: 477, 1963. Harken, D. E., and Taylor, W. J,: (:lirl. Obst. & Gynec. 4: 697, 1961. Harkins, J. L.: Clin. Obst. & Gynec. 6: :179, 1963. Hudspeth, A. S., Cordell, A. R., and Johnston, F. R.: Circulation 27: 796, lY6:?. Hufnagel, C. A., Villegas, P. D.. .md Nahas, H.: Ann. Surq. 147: 636, 1958 Igna, E. J., Detrick, M. F., Lam, C. R.. Keyes, J. W., and Hodgkinson, C:. P.: AM. J. OBST. & GYNEC. 71: 1024: 1956. Johnson, J., Kirby, C. K., Blakemore, M‘. S., Zinsser, H. F., Joyner, C. R.: and Hr+ wig, J.: Ann. Surg. 157: 902, 1963. Kaufman, J., and Ruble, P. E.: Ann. 1111. Med. 48: 1157, 1958. Kay, C. F., and Smith, K.: Am, J, Ca,diol. 12: 293, 1963. Kay, E. B., Mendelsohn, D., and Zimmerman, H. A.: Circulation 23: 813, 1961. Kay, E. B., and Zimmerman, H. A.: Am. J. Cardiol. 13: 112, 1964. Kay, E. B., and Zimmerman, I-I. A : ,411~ T. Cardiol. 10: 1. 1962. E. B., Zimmerman, H. A., and Mendelsohn, D.: Circulation 27: 767. 1963. Kay, J. H., Magidson, O., and Meihaus, J. E.: Am. J. Cardiol. 9: 300, 1962. Keith, T. A., Fowler, N. O., Helmsworth, J. A., and Gralnick, H.: Am. J. Med 34: 308, 1963. Kirklin, J. W., Weidman, W. H., Burroughs, J. T.? Burchell, H. B., and Wood, E II.: Circulation 13: 825, 1956. Landesman. R., and Miller, M. M.: Obsr. & Gynec. 21: 40, 1963. Lane, R. E., and Andelman, S. I,.: Anr. J, OBST. & GYNEC. 85: 52, 1963. Lee, W. H., Jr.. and Pate, J. W.: C; 1’ 28: 78, 1963. Lewis. F. J.: Surg. Gynec. Pr Obst. 116: 131, 1963. Lryse, R., Ofstun, M., Dillard, D. H., and Merendino, K. A.: J. A. M. A. 176: 1009, 1961. Lillehei, C. W., Long. D. M., Bilgutay. .4. M., and Cuello, L.: Circulation 26: 751: 1962. Logan, A., Lowther, C. P., and T~lrn~, R. W. D.: Lancet 1: 443. 1962. Logan, A., Lowther, C. P., and Turnrr, R. W. D.: Am. Heart J. 65: 135, 1963. Logan, A., and Turner, R. W. D.: I.ancet 1: 1286, 195?.

Kay,

162

Ueland Am.

87. 88. 89. 90. 91.

92.

93.

94. 95. 96.

97. 98.

99. 100. 101.

102. 103. 104.

105. 106. 107.

108.

109. 110. 111. 112. 113. 114.

Lowther, C. P., and Turner, R. W. D.: Brit. M. J. 1: 1027, 1962. Lowther, C. P., and Turner, R. W. D.: Brit. M. J. 1: 1102, 1962. Lowther, C. P., and Turner, R. W. D.: Am. Heart J. 65: 427, 1963. MacCallum, W. G., and McClure, R. D.: Bull. Johns Hopkins Hosp. 17: 260, 1906. Maim, J. R., Bowman, F. O., Jameson, A. G., Ellis, K., Griffiths, S. P., and Blumenthal, S.: Circulation 27: 805, 1963. Mason. 1.: In discussion of Stabler. F. E.. Szekely, P.: J. Obst. & Gynaec. Brit. Emp: 59: 569, 1952. Mauck, H. P., Jr., Lester, R. G., McCue, C. M., and Bosher, L. H.: Circulation 26: 758, 1962. McGeorge, M., and Rodda, R.: New Zealand M. J. 62: 261, 1963. McGoon, D. C.: Surgery 53: 372, 1963. McGoon, D. C.: In discussion of Effler, D. B., Groves, L. K., and Favaloro, R.: Arch. Surg. 88: 154, 1964. McGoon, D. C., and Moffit, E. A.: J. Thoracic & Cardiovas. Surg. 46: 162, 1963. Mendelson, C. L.: Cardiac Disease in Pregnancy: Medical Care, Cardiovascular Surgery and Obstetric Management as Related to Maternal and Fetal Welfare, Philadelphia, 1960, F. A. Davis Company. Mendelson, C. L.: Obst. & Gynec. 4: 603, 1961. Merendino, K. A.: Personal communication. Metcalfe, J., and Ueland, K.: The Heart and Pregnancy. In Logue, B., and Hurst, J. W., editors: Heart Disease, New York, McGraw-Hill Book Company, Inc. (In press. ) Mitchel, S. C.: Circulation 28: 770, 1963. Morrow, A. G., and Braunwald, N. S.: J. Thoracic & Cardiovas. Surg. 41: 225, 1961. Morrow, A. G., Clark, W. D., Harrison, D. C., and Braunwald, E.: Circulation 28: 772, 1963. Morse, D. P., Hirose, T., and Bailey, C. P.: Arch. Surg. 85: 198, 1962. Mortensen, J. D., and Ellsworth, H. S.: Circulation 28: 773, 1963. Mulder, D. G., Kattus, A. A., Jr., Fonkalsrud, E. W., and Longmire, W. P.: J. Thoracic & Cardiovas. Surg. 46: 468, 1963. Muller, W. H., Jr.: In discussion of Mulder, D. G., Kattus, A. A., Jr., Fonkalsrud, E. and Longmire, W. P.: J. Thoracic w., & Cardiovas. Surg. 46: 479, 1963. Neill, C. A., and Swanson, S.: Circulation 24: 1003, 1961. Nichols, H. T., Blanco, G., Adam, A., and Morse, D. P.: Circulation 26: 768, 1962. Nichols, H. T., Blanco, G., Uricchio, J. F., and Likoff, W.: Arch. Surg. 82: 128, 1961. Nichols, H. T., Morse, D. P., Blanco, G., and Adam, A.: Circulation 28: 779, 1963. O’Driscoll, M. K., Barry, A. P., and Drury, M. I.: Brit. M. J. 2: 1090, 1957. Penman, H. G., and Whitty, R. H.: Brit. Heart J. 70: 141, 1963.

115. 116. 117. 118. 119. 120.

121.

122.

123. 124.

125. 126. 27.

128.

129. 130.

131.

132.

133. 134. 135. 136. 137.

138. 139. 140. 141.

142.

May 1, 13b-l J. Obst. & Gynrc.

Primose, T.: Clin. Obst. & Gynec. 6: 893, 1963. Reid, J. M., Berger, R. L., and Stevenson, J. G.: Brit. M. J. 2: 1197, 1960. Riker, W. L.: S. Clin. North America 43: 113, 1963. Rowbotham, G. F., Bell, K., Akenhead, J., and Cairns, A.: Lancet 1: 1016, 1957. Salvaggio, A. T.: Harper Hosp. Bull. 17: 74, 1959. Scannell, J. G., Burke, J. F., Saidi, F., and Turner, J. D.: J. Thoracic & Cardiovas. Surg. 40: 723, 1960. Scannell, J. G., Shaw, R. S., Burke, J. F., Austen, W. G., and Saurbrey, J. S.: Circulation 27: 772, 1963. Shumacker, H. B., Jr.: In discussion of Effler, D. B., Groves, L. K., and Favaloro, R.: Arch. Sure. 88: 153. 1964. Smith, Blanc;: Arch. ‘Dis. Childhood 38: 151, 1963. Soulie, P., Acar, J., Degeorges, M., and Barrillon, A.: Arch. mal. coeur 54: 361, 1961. Souttar, H. S.: Brit. M. J. 2: 603, 1923. Stander, H. J., and Kuder, K.: J. A. M. A. 108: 2092, 1937. Starr, A.: IN discussion of Ellis, F. H., Jr., McGoon. D. C.. Brandenburg. R. 0.. and Kirklin, ‘J. W.: ‘J. Thoracic ‘& Cardiovas. Surg. 46: 495, 1963. Starr, A.: In discussion of Mulder, D. G., Kattus, A. A., Jr., Fonkalsrud, E. W., and Longmire, W. P.: J. Thoracic & Cardiovas. Surg. 46: 477, 1963. Starr, A., Edwards, M. L., and Griswold, H. E.: Progr. Cardiovas. Dis. 5: 298, 1962. Starr, A., Edwards, M. L., McCord, C. W., and Griswold. H. E.: Circulation 27: 779. 1963. ’ Starr, A., Edwards, M. L., McCord. C., Wood, J., Herr, R., and Griswold, H. E.: Circulation 28: 812, 1963. Steinmetz. G. P.. Tr.. Anderson. A. M.. Cobb, L. ‘A., Bruce,“R: A., and Merendinoj K. A.: Progr. Cardiovas. Dis. 5: 280, 1962. Sterns, L. P., Bitash, L. P., and Lillehei, C. W.: Am. 1. Cardiol. 13: 153. 1964. Stromme,” W. B., and Kuder, K.: Asr. J. OBST. & GYNEC. 52: 264, 1946. Sutherland, A. M., and Bruce, D. F.: J. Obst. & Gynaec. Brit. Comm. 69: 99, 1962. Szekely, P., and Snaith, L.: J. Obst. & Gynaec. Brit. Comm. 70: 69, 1963. Tenney, B., and Little, B.: Clinical Obstetrics, Philadelphia, 1961, W. B. Saunders Company. Tuffier, T.: Surgery 2: 249, 1914. VanderVeer, J. B., and Kuo, P. T.: Am. Heart J. 39: 2, 1950. Wade, G., Nicholson, W. F., and Jones. A. M.: Lancet 1: 559, 1958. ’ Winter. W. R.. Carmichael. D. B.. Baronofsky, i. D., and Baker, W. S.: AM. j. OBST. & GYNEC. 76: 572, 1958. Wooley, Cl. F., Runco, V., Levin, H. S., and Ryan, J. M.: Circulation 24: 1075, 1961.