- Email: [email protected]
Open heart surgery during pregnancy
art surger W-ILLIAM
6.
El.
C.
New
Haven,
MEFFERT,
STANSEL,
JR.,
M.D. M.D.”
Connecticut
Open heart surgery is now more frequently utilized to treat severely disabled pregnant patients with surgically correctable cardiac lesions. Review of the literature and personal communications reveals only 11 pregnant patients undergoing successful surgery involving cardiopulmonary bypass with subsequent delivery of normal infants. Two additional cases are reported from the Yale-New Haven Medical Center. The potential and actual fetal hazards appear multiple, but as yet their precise mechanisms of action remain undetermined.
IX T H I s country the recorded incidence of heart disease in pregnancy is 2.3 and 3.7 per cent in two recent large series.ll ’ According to these authors the vast majority of heart disease (84 and 93 per cent, respectively) is secondary to rheumatic fever, with congenital defects accounting for considerably fewer cases. In recent years cardiac surgery has contributed significantly to the over-all management of selected patients not responding successfully to medical measures. The earliest reports of cardiac surgery performed during pregnancy appeared in 1952 when Brock,” Cooley and Chapman,4 Logan and Turner,5 and Masons reported a total of 11 patients undergoing closed mitral commissurotomy while pregnant, with one maternal death and one premature delivery. Since 1952 reports of mitral commissurotomy in pregnancy have increased in number, and several reports of open heart surgery with the use of extracorporeal circulation have appeared. Leyse and associates7 in 1958 reported the correction of congenital aortic stenosis with a 20 minute period of extracorporeal circulation in a 4 month pregnant patient. The pregnancy terminated successfully but the
Fromthe Departmentof Surgery,Yale University
School
of Medicine.
“Reprint requests to Department Surgery, 333 Cedar Street, New Connecticut 06510.
of Haaen,
infant subsequently died with multiple congenital anomalies. One year later Dubourg and associates8 corrected congenital pulmonary stenosis and a ventricular septal defect with extracorporeal circulation in a 3 month pregnant patient. Surgery was followed by a spontaneous abortion at 6 months. No description of the fetus is given. In 1963, Lee and Pate9 repaired a leaking traumatic aneurysm of the aortic arch in a 5 month pregnant patient with a 45 minute perfusion, and a normal term infant was born later. The same year Kay and SmithlO reported open heart surgery in 2 Class 4 pregnant patients, with one maternal and 2 fetal deaths. More successful reports include Braunwald)P series of 3 patients in their first trimester of pregnancy undergoing open heart corrections of septal defects and subsequently being delivered of normal term infants and Jacobs, Cooley, and Goen’P” description of 3 successful open heart operations with survival of each patient, but with subsequent spontaneous abortion in one. Personal communication with this author reveals a total of 5 pregnant patients subjected to open heart surgery with subsequent delivery of normal children. Recently Mannix and Mahajan13 have reported on 3 pregnant women undergoing successful open heart surgery, with 2 subsequently aborting and one being delivered of a normal child. This year Kozam and associates*4 have described open mitral commissurotomy in a 36-year-
Volume Number
Open
102 8
old pregnant patient with successful termination of pregnancy and a healthy baby boy. Recently on the cardiovascular service of the Yale-New Haven Medical Center, we have successfully corrected congenita1 cardiac defects lin 2 pregnant patients and both have gone on to delivery of normal full-term infants. Case
reports
Case 1. Mrs. C. S. is a 25-year-old woman with a cardiac murmur noted since birth. At age 10 a chest film revealed a prominent pulmonary artery and increased pulmonary vascular markings. Electrocardiogram revealed an interventricular conduction defect. At age 21, right heart catheterization was performed. The catheter passed through an atria1 septal defect and 18-28 showed a pulmonary artery pressure of 6-11 mm. Hg and a right ventricular pressure of 34/6-g. The left-to-right shunt was 11.4 liters per minute. Angiogram revealed a normal pulmonary outflow tract. The patient subsequently had a successful pregnancy, during which time she experienced minimal palpitations but had a postpartum psychosis. She was admitted in January, 1966, for correction of her defect and was unknowingly pregnant at that time. Physical examination revealed no cardiac enlargement but right ventricular activity was slightly increased and the second sound was widely split. In addition, there was a Grade 3/6 ejection systolic murmur along the left sternal border and a Grade 3/6 holosystolic murmur at the cardiac apex. A third heart sound was heard along the left sternal border. revealed left auricular Electrocardiogram hypertrophy and left axis deviatian with a first degree A-V block and probable left ventricular hypertrophy. Liver function tests, electrolytes, blood urea nitrogen, free blood sugar, calcium and phosphorus, complete blood count, coagulation studies, land serologic test for syphilis were all within normal limits. Urine culture showed no growth an.d nose and throat culture revealed normal flora. On Jan. 11, 1966, a primary septal defect was closed with a Teflon cloth patch after suture repair of the cleft mitral valve. The patient’s postoperative course was uneventful and she was discharged on Jan. 25, 1966. She was subsequentl; found to be pregnant and delivered a
heart surgery in pregnancy
1117
normal 3.4 kilogram baby girl on Sept. 29, 1966. This child now weighs 8.6 kilograms. She is active and at 15 months of age walks well. Case 2. Mrs. A. P. is a 23-year-old woman who contracted rheumatic fever at age 8. Frequent attacks of arthritis occurred during adolescence and at age 15 she was told she had a heart murmur. Over the next few years she developed shortness of breath with exertion, pedal edema, and nocturia. When this young woman was first seen in this center and physical examination revealed a Grade 3/6 systolic murmur at the apex with a Grade l/4 blowing diastolic murmur along the left sternal border. P, was much louder than A,. Chest films revealed left atria1 enlargement and electrocardiogram showed right axis deviation. She subsequently became pregnant and developed severe congestive failure when 4 months pregnant. Because medical measures failed to adequately relieve her and an abortion was not wanted, she was accepted for a closed mitral commissurotomy at that time. At operation the mitral orifice was 1.2 cm. diameter. Slight insufficiency was noted following commissurotomy. Left atria1 pressure was 300 mm. saline prior to the commissurotomy and 150 mm. following operation. She subsequently had an uneventful pregnancy, a normal delivery, and a healthy baby. Approximately 2 years later she once again presented 4 months pregnant in mild congestive heart failure. Therapeutic abortion was successfully carried out. Cardiac catheterization was performed 4 months later and showed a right ventricular pressure of 40/6 mm. Hg with 64 per cent 0, saturation. The pulmonary artery pressure was 38/16 mm. Hg with a mean pressure of 22. The mean wedge pressure was 15 mm. Hg. Six months later she again presented with congestive heart failure, moderately severe, and was again pregnant in the third month. Medical measures were not successful in controlling the failure and abortion was not wanted. Therefore, she was once again accepted for cardiac surgery. On physical examination she presented as an anxious woman with a blood pressure of 130/70, a regular pulse of 88, and respirations of 20 per minute. RBles were heard at both lung bases and the point of maximum impulse was in the fifth intercostal space 2 cm. outside the midclavicular line. A diastolic thrill was present at the apex and a right ventricular heave seen across the precordium. A Grade 2/6 systolic murmur was
1118
Meffert
and
Stansel
at the apex and a Grade 5/6 diastolic rumble was heard in the same region. The first heart sound was accentuated at the apex and the second sound was maximal in the second left intercostal space. Abdominal examination revealed the liver at the right costal margin and tbe uterus 2 cm. below the umbilicus. The lower extremities had a trace of pedal edema bilaterally. Laboratory studies included a 10,750 white blood count and a hematocrit of 34 per cent. The blood urea nitrogen, electrolytes, calcium and phosphorus, prothrombin time, partial thromboplastin time, and urinalysis were within normal limits. The C-reactive protein was 1.5 mm. and the antistreptolysin CJ titer less than 50. The ECG showed a diphasic P in V, and V, w-ith a right axis and the S-T segments abnormally depressed and T waves inverted, low or diphasic in II, III, aV,, V,-,. On Nov. 18, 1965, with the aid of cardiopulmonary bypass, the heart was fibrillated and the left atrium explored. The mitral valve was found stenotic but competent. A Tubbs dilator was inserted into the mitral orifice which was split to 3.6 cm. diameter. No mitral insufficiency was produced. The patient’s postoperative course was satisfactory and she continued her pregnancy to term with delivery of a normal male infant on Jan. 9, 1966, weighing 3.29 kilograms. This child walked well at one year of age and now is a normal, active 22-month-old boy. present
Cemmeat The role of open heart surgery in producing congenital malformations or inducing abortions remains uncertain. It seems likely that the incidence of abnormalities following this surgery is increased over the %pontaneous” incidence in the general population of 7.5 per cent as reported by McIntosh and associates.lj McMusickr6 found a 1.46 per cent incidence of cardiac anomalies in offspring of parents with congenital cardiac lesions and it has been suggested that women with acquired heart disease also have an increased incidence of anomalies in their offspring. rr In addition, considering previous reports, it appears that surgery in pregnant particularly open heart surgery, patients, carries with it a risk of causing defects in the unborn child. Although the mechanism of anomaIy or
abortion production remains unknown, several factors should he considered. It is well known that internal organs in the fetus are formed at two months and changes after this are the result of growth and development. Obviously it is wise to avoid surgery during this early developmental period if pregnancy is known to exist. Factors potentially dangerous to the fetus which are inherent in cardiopulmonary bypass should be considered. Perfusion of the pelvis during bypass is not normally pulsatile; perhaps this departure from normal is important. However, flow distal to coarctations of the aorta is not pulsatile in the usual sense and yet PritchardI’ reviewed 208 cases of pregnant women who had coarctations and found the ‘normal” expected a.bortion rate. However, in 1965, Mortensen and EllsworthI reviewed 32 pregnancies in 9 women with coarctations and found 17 spontaneous miscarriages and one stillborn fetus, while in 21 pregnancies in 8 women with surgically resected coarctations, there were only 2 spontaneous miscarriages. It has been shown by Assali, Rauramo, and Peltoner? and others before them that the fetus lives in a relatively hypoxic state. Their measurements indicate fetal umbilical blood flow remains relatively constant at 11 ml. per 100 grams fetal weight per minute from the twelfth to the twenty-eighth week of gestation and fetal arterial oxygen saturation varies between 52 and 65 per cent. In spite of this !ow saturation, adequate oxygen supply is available when the previously mentioned blood flow is maintained. EIowever, if the uterine blood flow were marginal, as perhaps caused by lack of pulsatiIe flow or opening of uterine A-V shunts or uterine arterial spasm during bypass, critical fetal hypoxia might occur. The real, but unconfirmed possibility that particulate or bubble emboli or sludging of blood might interfere with placental circulation during bypass awaits future investigation. Investigation by Gabel, Romney, and Kaneokazl in dogs has shown that maternal hemorrhage produces a significant decrease in uterine blood flow and fetal skin and
Volume Number
102 8
skeletal muscle oxygen tension, even when the maternal arterial PO, is unchanged. When these authors infused Vasoxyl, the maternal blood pressure was increased as would be expected. But, in addition, this infusion produced a significant decrease in uterine blood flow, uterine tissue PO,, and fetal tissue PO, with resultant marked fetal hypoxia and bradycardia. Therefore, it appears particularly important in the pregnant patient to replace blood accurately as it is lost and to avoid the use of vasopressors, if possible. The prone position significantly interferes with venous return in the third trimester, as demonstrated by Quilligan and Tyler’s22 finding of a 13.5 per cent increase in cardiac output when a patient late in pregnancy is turned from a supine to lateral position. Aside from. compression of the vena cava by positioning, it is possible that cannulation of the inferior vena cava during cardiopulmonary bypass might partially obstruct this vessel. The harmful effects of inferior vena cava obstruction have been amply demonstrated experimentally. Howard and GoodsonZ3 compressed the inferior vena cava in dogs at term and produced abruptio placentae, and HaynesZ4 has produced similar effects in the rabbit. While such gross damage obviously does not often take place during perfusion, nevertheless, minor degrees of inferior vena cava compression during surgery may produce subtle placental changes secondary fetal abnorand malities. Such adjuvants as antibiotics and anticoagulants must not be overlooked as potentially dangerous to the fetus. In 1963, Carter and Wilsonz5 studied 387 pregnancies from their practice. In 13, the mother was given antibiotics (unidentified) during the first trimester. One of these 13 aborted and 6 had malformed babies. Although this series may have been artificially selected to some extent, other authors have published supportive data. WalfordZ6 compared 954 pregnancies in which antibiotics (again not identified) were not used with 50 pregnancies in which they were used dur-
Open
heart
surgery
in pregnancy
1119
ing the first .trimester. He found that pregnancies in which these agents had been used rcpregnancy wastage” suffered a higher (abortions, stillbirths, malformations, and neonatal deaths) that was statistically significant at the 5 per cent level, That anticoagulation carries with it a risk to the fetus is well known. Mahairas and Weingoldz7 reported a case of pulmonary embolism in pregnancy treated with warfarin sodium (Coumadin) ~ While on this anticoagulant, loss of fetal movement and heart sounds occurred. The patient had a second embolus while under treatment and was subjected to hysterotomy and inferior vena cava ligation. At operation the placenta was partially detached from the uterine wall and poorly formed clot was expressed from it. The 1,300 gram fetus exhibited marked autolysis, but hemorrhage was found in the thymus. This author reports 11 other cases involving fetal loss with warfarin and bfs-hydroxycoumarin treatment. Heparin, with its larger molecular size (molecular weight, 20,000) as compared to bis-hydroxycoumarin (molecular weight, l,OOO), appears incapable of crossing the placenta. These authors could find no case reports of fetal loss during heparin treatment in pregnancy. Jennings and Hodgkinsor? also point out the dangers of warfarin in pregnancy and add to the general consensus of recent years that heparin is a safer anticoagulant in the pregnant patient. Following open heart surgery and the conclusion of anticoagulation, dangers for the fetus may persist. Transient septicemia during surgery may set up a focus of infection in the fetus or fetal membranes. What immunologic effect the blood administered during open heart surgery may have on the fetus can only be surmised at this time. The exact mechanisms and precise dangers of almost all the possible causes of fetal anomalies and deaths associated with open heart surgery remain to be determined by future investigation. Undoubtedly, many unpublished cases exist. It is hoped that subsequent larger cumulative reports may shed further light on this subject.
1120
Meffert
December 5 1968 Am. J. Obst. & dynec.
and Stansef
REFERENCES
1.
2.
3.
Burwell, C. S., and Metcalfe, Jr.: Heart Disease and Pregnancy, Physiology and M[anagement, Boston, 1958, Little, Brown & Gompany. Mendelson. z C. L.: Cardiac Disease in Preenancy: Medical Care, Cardiovascular Suygery and Obstetric iManagement as Reiated to Maternal and Fetal Welfare, Philadelphia, 1960, F. A. Davis Company. Brock, R. C.: Proc. Roy. Sot. Med. 45:
14. Kozam, 15. 16. 17.
538, 1952. 4.
5. 6. 7. 8. 9. 10. II. 12. 13.
Cooley, D. A., and Chapman, D. W.: J. A. M. A. 150: 1113, 1952. Loga,n, A., and Turner, R.: Lancet 2: 1286, 1952. Mason, J.: In discussion of Stabler, F. E., and Szekely, P.: Jo Obst. & Gynaec. Brit. Emp. 59: 569: 1952. Leyse, R., Ofstun, M., Dillard, D. H., and Merendino, K. A.: J. A. M. A. 176: 1009, 1961. Dubourg, G., Broustet, P., Bricaud, J., Fontan, F., Trarieux, M., and Fontaniile, P.: Arch. mal. coeur 52: 1389, 1959. Lee, W. H., Jr., and Pate, J. W.: GP 28: 78, 1963. Kay, C. F., and Smith, K.: Am. J. Cardioi. 12: 293, 1963. Braunwald, N. S.: In Ueland, K.: AM. Jo OBST. & GYNEC. 92: 148. 1965. Jacobs, ‘W, M., Cooley, ‘D., and Goen, G. P.: Obst. & Gynec. 25: 167, 1965. Mannix; E. P., and Mahajan, D. R.: J. Thoracic & Cardiovas. Surg. 53: 592, 1967.
18. 19. 20.
R. L., Conklin, E. F., GianneBi, S., Serey, P., and Ghu, D.: J. Thoracic & Cardiovas. Surg. 53: 587, 1967. McIntosh, R., Merritt, K. K., Richards, M. R., Samuels, M. H., and Bellows, M. T.: Pediatrics 14: 505, 1954. McKusick, V. A.: Mod. Concepts Card. Dis. 28: 535, 551; 1959. Willis, R. A.: Borderland of Embryoiogy and Pathology, London, 1958, Butterworth & Company, Ltd. Pritchard, J. A.: Obst. & Gynec. Surv. 8: 775. 1953. Mortensen, J. D., and Ellsworth, H. C.: .T. A. M. -4. 191: 596, 1965. kssali, N. S., Rauramo, L., and Peltonen, T.: AX 1. OBST. & GYNEC. 79: 86. 1960. Gabel, P. V., Romney, S. L., and Kaneoka, T.: S. Forum 13: 394, 1962. Quilligan, E. J., and Tyler, C.: A,n. J. OBST. & GYNEC. 78: 465. 1959. Howard, B. K., and Goodson, J. H.: Obst. & Gynec. 2: 442, 1953. Haynes, D. M.: AM. J. QBST. & GYNEC. 85: 626, 1963. Carter; M. P., and Wilson, F.: Lancet 1: 1267, 1963. WaIford, P. A.: Lancet 2: 298, 1963. Mahairas, G. H., and Weingold, A. B.: As%. J. OBST. & GYNEC. 85: 234, 1963. Jennings, J. A., and Hodgkinson, C. P.: Obst. t Gynec. 24: 85, 1964. ”
21. 22. 23. 24. 25. 26. 27. 28.
6.
El.
C.
New
Haven,
MEFFERT,
STANSEL,
JR.,
M.D. M.D.”
Connecticut
Open heart surgery is now more frequently utilized to treat severely disabled pregnant patients with surgically correctable cardiac lesions. Review of the literature and personal communications reveals only 11 pregnant patients undergoing successful surgery involving cardiopulmonary bypass with subsequent delivery of normal infants. Two additional cases are reported from the Yale-New Haven Medical Center. The potential and actual fetal hazards appear multiple, but as yet their precise mechanisms of action remain undetermined.
IX T H I s country the recorded incidence of heart disease in pregnancy is 2.3 and 3.7 per cent in two recent large series.ll ’ According to these authors the vast majority of heart disease (84 and 93 per cent, respectively) is secondary to rheumatic fever, with congenital defects accounting for considerably fewer cases. In recent years cardiac surgery has contributed significantly to the over-all management of selected patients not responding successfully to medical measures. The earliest reports of cardiac surgery performed during pregnancy appeared in 1952 when Brock,” Cooley and Chapman,4 Logan and Turner,5 and Masons reported a total of 11 patients undergoing closed mitral commissurotomy while pregnant, with one maternal death and one premature delivery. Since 1952 reports of mitral commissurotomy in pregnancy have increased in number, and several reports of open heart surgery with the use of extracorporeal circulation have appeared. Leyse and associates7 in 1958 reported the correction of congenital aortic stenosis with a 20 minute period of extracorporeal circulation in a 4 month pregnant patient. The pregnancy terminated successfully but the
Fromthe Departmentof Surgery,Yale University
School
of Medicine.
“Reprint requests to Department Surgery, 333 Cedar Street, New Connecticut 06510.
of Haaen,
infant subsequently died with multiple congenital anomalies. One year later Dubourg and associates8 corrected congenital pulmonary stenosis and a ventricular septal defect with extracorporeal circulation in a 3 month pregnant patient. Surgery was followed by a spontaneous abortion at 6 months. No description of the fetus is given. In 1963, Lee and Pate9 repaired a leaking traumatic aneurysm of the aortic arch in a 5 month pregnant patient with a 45 minute perfusion, and a normal term infant was born later. The same year Kay and SmithlO reported open heart surgery in 2 Class 4 pregnant patients, with one maternal and 2 fetal deaths. More successful reports include Braunwald)P series of 3 patients in their first trimester of pregnancy undergoing open heart corrections of septal defects and subsequently being delivered of normal term infants and Jacobs, Cooley, and Goen’P” description of 3 successful open heart operations with survival of each patient, but with subsequent spontaneous abortion in one. Personal communication with this author reveals a total of 5 pregnant patients subjected to open heart surgery with subsequent delivery of normal children. Recently Mannix and Mahajan13 have reported on 3 pregnant women undergoing successful open heart surgery, with 2 subsequently aborting and one being delivered of a normal child. This year Kozam and associates*4 have described open mitral commissurotomy in a 36-year-
Volume Number
Open
102 8
old pregnant patient with successful termination of pregnancy and a healthy baby boy. Recently on the cardiovascular service of the Yale-New Haven Medical Center, we have successfully corrected congenita1 cardiac defects lin 2 pregnant patients and both have gone on to delivery of normal full-term infants. Case
reports
Case 1. Mrs. C. S. is a 25-year-old woman with a cardiac murmur noted since birth. At age 10 a chest film revealed a prominent pulmonary artery and increased pulmonary vascular markings. Electrocardiogram revealed an interventricular conduction defect. At age 21, right heart catheterization was performed. The catheter passed through an atria1 septal defect and 18-28 showed a pulmonary artery pressure of 6-11 mm. Hg and a right ventricular pressure of 34/6-g. The left-to-right shunt was 11.4 liters per minute. Angiogram revealed a normal pulmonary outflow tract. The patient subsequently had a successful pregnancy, during which time she experienced minimal palpitations but had a postpartum psychosis. She was admitted in January, 1966, for correction of her defect and was unknowingly pregnant at that time. Physical examination revealed no cardiac enlargement but right ventricular activity was slightly increased and the second sound was widely split. In addition, there was a Grade 3/6 ejection systolic murmur along the left sternal border and a Grade 3/6 holosystolic murmur at the cardiac apex. A third heart sound was heard along the left sternal border. revealed left auricular Electrocardiogram hypertrophy and left axis deviatian with a first degree A-V block and probable left ventricular hypertrophy. Liver function tests, electrolytes, blood urea nitrogen, free blood sugar, calcium and phosphorus, complete blood count, coagulation studies, land serologic test for syphilis were all within normal limits. Urine culture showed no growth an.d nose and throat culture revealed normal flora. On Jan. 11, 1966, a primary septal defect was closed with a Teflon cloth patch after suture repair of the cleft mitral valve. The patient’s postoperative course was uneventful and she was discharged on Jan. 25, 1966. She was subsequentl; found to be pregnant and delivered a
heart surgery in pregnancy
1117
normal 3.4 kilogram baby girl on Sept. 29, 1966. This child now weighs 8.6 kilograms. She is active and at 15 months of age walks well. Case 2. Mrs. A. P. is a 23-year-old woman who contracted rheumatic fever at age 8. Frequent attacks of arthritis occurred during adolescence and at age 15 she was told she had a heart murmur. Over the next few years she developed shortness of breath with exertion, pedal edema, and nocturia. When this young woman was first seen in this center and physical examination revealed a Grade 3/6 systolic murmur at the apex with a Grade l/4 blowing diastolic murmur along the left sternal border. P, was much louder than A,. Chest films revealed left atria1 enlargement and electrocardiogram showed right axis deviation. She subsequently became pregnant and developed severe congestive failure when 4 months pregnant. Because medical measures failed to adequately relieve her and an abortion was not wanted, she was accepted for a closed mitral commissurotomy at that time. At operation the mitral orifice was 1.2 cm. diameter. Slight insufficiency was noted following commissurotomy. Left atria1 pressure was 300 mm. saline prior to the commissurotomy and 150 mm. following operation. She subsequently had an uneventful pregnancy, a normal delivery, and a healthy baby. Approximately 2 years later she once again presented 4 months pregnant in mild congestive heart failure. Therapeutic abortion was successfully carried out. Cardiac catheterization was performed 4 months later and showed a right ventricular pressure of 40/6 mm. Hg with 64 per cent 0, saturation. The pulmonary artery pressure was 38/16 mm. Hg with a mean pressure of 22. The mean wedge pressure was 15 mm. Hg. Six months later she again presented with congestive heart failure, moderately severe, and was again pregnant in the third month. Medical measures were not successful in controlling the failure and abortion was not wanted. Therefore, she was once again accepted for cardiac surgery. On physical examination she presented as an anxious woman with a blood pressure of 130/70, a regular pulse of 88, and respirations of 20 per minute. RBles were heard at both lung bases and the point of maximum impulse was in the fifth intercostal space 2 cm. outside the midclavicular line. A diastolic thrill was present at the apex and a right ventricular heave seen across the precordium. A Grade 2/6 systolic murmur was
1118
Meffert
and
Stansel
at the apex and a Grade 5/6 diastolic rumble was heard in the same region. The first heart sound was accentuated at the apex and the second sound was maximal in the second left intercostal space. Abdominal examination revealed the liver at the right costal margin and tbe uterus 2 cm. below the umbilicus. The lower extremities had a trace of pedal edema bilaterally. Laboratory studies included a 10,750 white blood count and a hematocrit of 34 per cent. The blood urea nitrogen, electrolytes, calcium and phosphorus, prothrombin time, partial thromboplastin time, and urinalysis were within normal limits. The C-reactive protein was 1.5 mm. and the antistreptolysin CJ titer less than 50. The ECG showed a diphasic P in V, and V, w-ith a right axis and the S-T segments abnormally depressed and T waves inverted, low or diphasic in II, III, aV,, V,-,. On Nov. 18, 1965, with the aid of cardiopulmonary bypass, the heart was fibrillated and the left atrium explored. The mitral valve was found stenotic but competent. A Tubbs dilator was inserted into the mitral orifice which was split to 3.6 cm. diameter. No mitral insufficiency was produced. The patient’s postoperative course was satisfactory and she continued her pregnancy to term with delivery of a normal male infant on Jan. 9, 1966, weighing 3.29 kilograms. This child walked well at one year of age and now is a normal, active 22-month-old boy. present
Cemmeat The role of open heart surgery in producing congenital malformations or inducing abortions remains uncertain. It seems likely that the incidence of abnormalities following this surgery is increased over the %pontaneous” incidence in the general population of 7.5 per cent as reported by McIntosh and associates.lj McMusickr6 found a 1.46 per cent incidence of cardiac anomalies in offspring of parents with congenital cardiac lesions and it has been suggested that women with acquired heart disease also have an increased incidence of anomalies in their offspring. rr In addition, considering previous reports, it appears that surgery in pregnant particularly open heart surgery, patients, carries with it a risk of causing defects in the unborn child. Although the mechanism of anomaIy or
abortion production remains unknown, several factors should he considered. It is well known that internal organs in the fetus are formed at two months and changes after this are the result of growth and development. Obviously it is wise to avoid surgery during this early developmental period if pregnancy is known to exist. Factors potentially dangerous to the fetus which are inherent in cardiopulmonary bypass should be considered. Perfusion of the pelvis during bypass is not normally pulsatile; perhaps this departure from normal is important. However, flow distal to coarctations of the aorta is not pulsatile in the usual sense and yet PritchardI’ reviewed 208 cases of pregnant women who had coarctations and found the ‘normal” expected a.bortion rate. However, in 1965, Mortensen and EllsworthI reviewed 32 pregnancies in 9 women with coarctations and found 17 spontaneous miscarriages and one stillborn fetus, while in 21 pregnancies in 8 women with surgically resected coarctations, there were only 2 spontaneous miscarriages. It has been shown by Assali, Rauramo, and Peltoner? and others before them that the fetus lives in a relatively hypoxic state. Their measurements indicate fetal umbilical blood flow remains relatively constant at 11 ml. per 100 grams fetal weight per minute from the twelfth to the twenty-eighth week of gestation and fetal arterial oxygen saturation varies between 52 and 65 per cent. In spite of this !ow saturation, adequate oxygen supply is available when the previously mentioned blood flow is maintained. EIowever, if the uterine blood flow were marginal, as perhaps caused by lack of pulsatiIe flow or opening of uterine A-V shunts or uterine arterial spasm during bypass, critical fetal hypoxia might occur. The real, but unconfirmed possibility that particulate or bubble emboli or sludging of blood might interfere with placental circulation during bypass awaits future investigation. Investigation by Gabel, Romney, and Kaneokazl in dogs has shown that maternal hemorrhage produces a significant decrease in uterine blood flow and fetal skin and
Volume Number
102 8
skeletal muscle oxygen tension, even when the maternal arterial PO, is unchanged. When these authors infused Vasoxyl, the maternal blood pressure was increased as would be expected. But, in addition, this infusion produced a significant decrease in uterine blood flow, uterine tissue PO,, and fetal tissue PO, with resultant marked fetal hypoxia and bradycardia. Therefore, it appears particularly important in the pregnant patient to replace blood accurately as it is lost and to avoid the use of vasopressors, if possible. The prone position significantly interferes with venous return in the third trimester, as demonstrated by Quilligan and Tyler’s22 finding of a 13.5 per cent increase in cardiac output when a patient late in pregnancy is turned from a supine to lateral position. Aside from. compression of the vena cava by positioning, it is possible that cannulation of the inferior vena cava during cardiopulmonary bypass might partially obstruct this vessel. The harmful effects of inferior vena cava obstruction have been amply demonstrated experimentally. Howard and GoodsonZ3 compressed the inferior vena cava in dogs at term and produced abruptio placentae, and HaynesZ4 has produced similar effects in the rabbit. While such gross damage obviously does not often take place during perfusion, nevertheless, minor degrees of inferior vena cava compression during surgery may produce subtle placental changes secondary fetal abnorand malities. Such adjuvants as antibiotics and anticoagulants must not be overlooked as potentially dangerous to the fetus. In 1963, Carter and Wilsonz5 studied 387 pregnancies from their practice. In 13, the mother was given antibiotics (unidentified) during the first trimester. One of these 13 aborted and 6 had malformed babies. Although this series may have been artificially selected to some extent, other authors have published supportive data. WalfordZ6 compared 954 pregnancies in which antibiotics (again not identified) were not used with 50 pregnancies in which they were used dur-
Open
heart
surgery
in pregnancy
1119
ing the first .trimester. He found that pregnancies in which these agents had been used rcpregnancy wastage” suffered a higher (abortions, stillbirths, malformations, and neonatal deaths) that was statistically significant at the 5 per cent level, That anticoagulation carries with it a risk to the fetus is well known. Mahairas and Weingoldz7 reported a case of pulmonary embolism in pregnancy treated with warfarin sodium (Coumadin) ~ While on this anticoagulant, loss of fetal movement and heart sounds occurred. The patient had a second embolus while under treatment and was subjected to hysterotomy and inferior vena cava ligation. At operation the placenta was partially detached from the uterine wall and poorly formed clot was expressed from it. The 1,300 gram fetus exhibited marked autolysis, but hemorrhage was found in the thymus. This author reports 11 other cases involving fetal loss with warfarin and bfs-hydroxycoumarin treatment. Heparin, with its larger molecular size (molecular weight, 20,000) as compared to bis-hydroxycoumarin (molecular weight, l,OOO), appears incapable of crossing the placenta. These authors could find no case reports of fetal loss during heparin treatment in pregnancy. Jennings and Hodgkinsor? also point out the dangers of warfarin in pregnancy and add to the general consensus of recent years that heparin is a safer anticoagulant in the pregnant patient. Following open heart surgery and the conclusion of anticoagulation, dangers for the fetus may persist. Transient septicemia during surgery may set up a focus of infection in the fetus or fetal membranes. What immunologic effect the blood administered during open heart surgery may have on the fetus can only be surmised at this time. The exact mechanisms and precise dangers of almost all the possible causes of fetal anomalies and deaths associated with open heart surgery remain to be determined by future investigation. Undoubtedly, many unpublished cases exist. It is hoped that subsequent larger cumulative reports may shed further light on this subject.
1120
Meffert
December 5 1968 Am. J. Obst. & dynec.
and Stansef
REFERENCES
1.
2.
3.
Burwell, C. S., and Metcalfe, Jr.: Heart Disease and Pregnancy, Physiology and M[anagement, Boston, 1958, Little, Brown & Gompany. Mendelson. z C. L.: Cardiac Disease in Preenancy: Medical Care, Cardiovascular Suygery and Obstetric iManagement as Reiated to Maternal and Fetal Welfare, Philadelphia, 1960, F. A. Davis Company. Brock, R. C.: Proc. Roy. Sot. Med. 45:
14. Kozam, 15. 16. 17.
538, 1952. 4.
5. 6. 7. 8. 9. 10. II. 12. 13.
Cooley, D. A., and Chapman, D. W.: J. A. M. A. 150: 1113, 1952. Loga,n, A., and Turner, R.: Lancet 2: 1286, 1952. Mason, J.: In discussion of Stabler, F. E., and Szekely, P.: Jo Obst. & Gynaec. Brit. Emp. 59: 569: 1952. Leyse, R., Ofstun, M., Dillard, D. H., and Merendino, K. A.: J. A. M. A. 176: 1009, 1961. Dubourg, G., Broustet, P., Bricaud, J., Fontan, F., Trarieux, M., and Fontaniile, P.: Arch. mal. coeur 52: 1389, 1959. Lee, W. H., Jr., and Pate, J. W.: GP 28: 78, 1963. Kay, C. F., and Smith, K.: Am. J. Cardioi. 12: 293, 1963. Braunwald, N. S.: In Ueland, K.: AM. Jo OBST. & GYNEC. 92: 148. 1965. Jacobs, ‘W, M., Cooley, ‘D., and Goen, G. P.: Obst. & Gynec. 25: 167, 1965. Mannix; E. P., and Mahajan, D. R.: J. Thoracic & Cardiovas. Surg. 53: 592, 1967.
18. 19. 20.
R. L., Conklin, E. F., GianneBi, S., Serey, P., and Ghu, D.: J. Thoracic & Cardiovas. Surg. 53: 587, 1967. McIntosh, R., Merritt, K. K., Richards, M. R., Samuels, M. H., and Bellows, M. T.: Pediatrics 14: 505, 1954. McKusick, V. A.: Mod. Concepts Card. Dis. 28: 535, 551; 1959. Willis, R. A.: Borderland of Embryoiogy and Pathology, London, 1958, Butterworth & Company, Ltd. Pritchard, J. A.: Obst. & Gynec. Surv. 8: 775. 1953. Mortensen, J. D., and Ellsworth, H. C.: .T. A. M. -4. 191: 596, 1965. kssali, N. S., Rauramo, L., and Peltonen, T.: AX 1. OBST. & GYNEC. 79: 86. 1960. Gabel, P. V., Romney, S. L., and Kaneoka, T.: S. Forum 13: 394, 1962. Quilligan, E. J., and Tyler, C.: A,n. J. OBST. & GYNEC. 78: 465. 1959. Howard, B. K., and Goodson, J. H.: Obst. & Gynec. 2: 442, 1953. Haynes, D. M.: AM. J. QBST. & GYNEC. 85: 626, 1963. Carter; M. P., and Wilson, F.: Lancet 1: 1267, 1963. WaIford, P. A.: Lancet 2: 298, 1963. Mahairas, G. H., and Weingold, A. B.: As%. J. OBST. & GYNEC. 85: 234, 1963. Jennings, J. A., and Hodgkinson, C. P.: Obst. t Gynec. 24: 85, 1964. ”
21. 22. 23. 24. 25. 26. 27. 28.