HEART DISEASEAND PREGNANCY PAUL SZEKELY,M.D. DESMOND G. JULIAN, M.D.

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TABLE

OF CONTENTS . . .

3

CLINICAL, RADIOL~GIC AND ECG CHANGES IN THE HEART AND CARDIAC PERFORMANCE ..........

.

8

RESPIRATORY SYSTEM

. . . 12

CARDIOVASCULAR

CLINICAL

PHYSIOLOGY OF PREGNANCY

.....

.............. .

ASPECTS OF HEART DISEASE AND PREGNANCY

RHEUMATIC

HEART DISEASE

THROMBOEMBOLIC CONGENITAL HYPERTENSIVE

DISEASE

DISORDERS

CARDIOMYOPATHY

CORONARY HEART DISEASE DISSECTING ANEURYSM PRIMARY PULMONARY

. . . 36

............

. . . 40

...........

. . . 52

............

AND PREGNANCY

. . . 13 . . . 26

...........

HEART DISEASE

.

. . . 57

.........

. . . 59

............

OF THE AORTA ........

. . . 61

........

. . . 62

HYPERTENSION

THE USE OF DRUGS AND OTHER AGENTS IN PREGNANCY INDICATIONS FOR TERMINATION

.

. . . 63

.

.

.

.

.

.

65

THE IMMPORTANCE OF PREGRAVIDITY ASSESSMENT OF THE CARDIAC STATE. ADVICE ON UNDERTAKING PREGNANCY OR CONTRACEPTION . . . . . .

.

.

.

.

.

66

2

OF PREGNANCY.

.

PAUL SZEKELY, M.D. is Honorary Consultant Cardiologist to the Newcastle Area Health Authority (teaching). He graduated from the Universities of Prague and Durham. He trained in General Medicine and Cardiology at the University Medical Clinic in Prague and the University Cardiology Clinic in Paris. Dr. Szekely has occupied the post of Consultant Cardiologist at Newcastle General Hospital from 1948 to 1975. His main research interests have been in the field of rheumatic heart disease, cardiac arrhythmias, cardiovascular pharmacology and cardiovascular problems in relation to pregnancy.

DESMOND G. JULIAN, M.D. is British Heart Foundation Professor of Cardiology, University of Newcastle upon Tyne. He graduated from Cambridge University and trained in Clinical Medicine at the Middlesex Hospital, London. His postgraduate training was at the National Heart Hospital, London, the Royal Infirmary, Edinburgh, and the Peter Bent Brigham Hospital in Boston. Dr. Julian has been cardiologist at Sydney Hospital and consultant physician to the Royal Infirmary, Edinburgh. His principal research interests are in the field of acute myocardial infarction and the arrhythmias associated with it, particularly in ventricular fibrillation.

CARDIOVASCULAR

PHYSIOLOGY

OF PREGNANCY

IMPORTANT PHYSIOLOGICAL CHANGES of adaptation take place in the cardiovascular and respiratory systems in normal pregnant women. Among the most important ones are an increase in cardiac output, in blood volume and in heart rate. Further alterations with relevance to cardiovascular hemodynamics are varying degrees of water retention, hormonal modifications and increase in general metabolism with a rise in oxygen consumption. These changes are usually well tolerated by patients 3

with a normal cardiovascular system and also by most women with organic heart disease. However, in a number of patients, serious complications appear in the course of pregnancy, which are either directly precipitated by the circulatory load or happen to develop at that particular time in the course of the natural history of the disease. Accordingly, the rational management of pregnant women with structural heart disease is to be based on the appreciation of the hemodynamic changes peculiar to pregnancy and on the evaluation of the clinicopathologic stage reached by the heart disease in its natural course. It is also relevant that the pregnant state modifies the pattern of hemodynamic responses to exercise. CARDIAC

OUTPUT

Data obtained by cardiac catheterization and by the use of indicator-dilution techniques and, more recently, by echocardiography have shown that the cardiac output begins to rise in the 1st trimester, possibly as early as the 10th week of gestation. At first, the increase is rapid, then the rate of increase becomes slower, and the maximum is probably reached by the 20th week.‘e3 It is estimated that the maximal rise is of the order of 30-40% above the nonpregnant level. More recent studies have also shown that the peak level is maintained until term when measurements are carried out in the lateral recumbent position.‘, 4* 5 Previous estimations of cardiac output that showed a fall in late pregnancy were carried out in the supine position. In this position, the gravid uterus compresses the inferior vena cava, which results in a decrease in the venous return to the right side of the heart. Radiologic studies have shown obstruction of the inferior vena cava at term in the supine position in about 90% of the cases.6 However, Metcalfe and UelandG maintain that the caval obstruction is only partially relieved by assuming the lateral recumbent position, as they found a decline in cardiac output near term in all body positions, although to a much lesser extent when the cardiac output was measured in the lateral recumbent position. The increase in cardiac output is brought about by an increase in stroke volume and in heart rate. In the early stages of pregnancy, the increase in stroke volume is the dominant factor, but at a more advanced stage of pregnancy the increase in heart rate is getting more pronounced and it begins to assume a more significant role than previously.2 Metcalfe and Ueland6 have pointed out that mild physical exercise results in a greater increase in cardiac output during pregnancy than in the nonpregnant state. This increase in cardiac output is proportionately greater than the increase in oxygen consumption resulting in a lower arteriovenous oxygen difference. 4

During labor, the cardiac output rises with each uterine contraction by about 20% or so, due mainly to an increase in stroke volume as a result of blood being expelled from the uterine vessels into the general circulation and increasing thereby the venous return.2 There is also a slight rise in cardiac output between uterine contractions, which has been attributed to pain and anxiety in view of the fact that it can be prevented by continuous epidural anesthesia.’ On the whole, it is generally accepted that the cardiac output, and indeed most hemodynamic values obtained in labor depend on the position of the patient just as it is the case during the whole of pregnancy. After delivery, there is an increase in cardiac output averaging 20%, caused by the shift of blood from the uteroplacental vascular system into the general circulation, but this increase can be rather variable, depending on the amount of blood loss at the time of delivery and also on the use of oxytocic drugs.’ As there is often bradycardia in the early puerperium, the postdelivery rise in cardiac output is virtually entirely due to the increase in stroke volume. The cardiac output returns to the pregravidic level gradually over a few weeks after delivery.’ Blood Volume

The increase in total maternal blood volume averages 40% above nonpregnant levels. There is, however, considerable individual variation3 The increase in plasma volume exceeds that in red cell volume with the result that the hemoglobin concentration falls during pregnancy. However, experience shows that the continuous administration of iron from early pregnancy assures an adequate hemoglobin level in terms of oxygen-carrying capacity of the maternal blood. Admittedly, not all pregnant women necessarily require prophylactic iron medication. Hypervolemia starts early in pregnancy, possibly well within the 1st trimester, but at a more gradual rate than the increase in cardiac output. According to Rovinsky,8 the plasma volume increases in single pregnancy to about 34% above the nonpregnant level at 21-24 weeks’ gestation and to about 49% between 33 and 36 weeks, and remains at this level until term. The pregravidic plasma volume level gives no indication regarding the rate of increase during pregnancy, but there appears to be a direct relationship between the degree of the increase in plasma volume and the birth weight of the newborn. Both plasma and red cell volume increments are higher in twin pregnancy than in single pregnancy, and they are also greater in the multigravidae than in the primigravidae.8 After a transient decrease in plasma volume in the immediate postdelivery period, the extent of which depends mainly on the amount of blood loss during the 3d stage of labor, there is a further increase in plasma volume, which is due partly to reabsorption of tissue fluid accumulated during pregnancy and part5

ly to the uterine blood being squeezed into the general circulation. The plasma volume returns to nonpregnant levels within a few weeks after delivery.8 HEART RATE

The resting heart rate increases during the earlier stages of pregnancy by about 10 beats per minute. As pregnancy advances there is a greater increase in heart rate, up to 15 beats per minute or more nearer term. 8, s Continuous recording of the heart rate during sleep showed similar findings.3 In twin pregnancy, the increase in heart rate begins earlier and at an accelerated rate, reaching a peak level of up to 40% above nonpregnant levels near term.8 ARTERIAL BLOOD PRESSURE

Most normal pregnant women display a slight fall in both systolic and diastolic pressures. The lowering of the blood pressure starts early, but it is most noticeable in midpregnancy, with a return to the original figures in the 3d trimester. At no time is there a rise in blood pressure under strictly normal conditions in spite of the increase in stroke volume, because of the significant reduction in the total peripheral vascular resistance and vasodilatation. In labor, the blood pressure, mainly systolic, rises with each uterine contraction, and the combination of the rise in mean arterial pressure and increase in cardiac output at this time is likely to increase the load on the left ventricle.’ INTRACARDIAC PRESSURES

Measurements of intracardiac pressures have not recorded uniform results. It would appear that there is a tendency to a rather modest increase in right ventricular end-diastolic and pulmonary artery pressures. lo The combination of a marked increase in pulmonary blood flow and a marginal increase in pulmonary artery pressure indicates, if anything at all, a fall in pulmonary vascular resistance. During labor, there is an increase in right atria1 pressure with each uterine contraction. VENOUS HEMODYNAMICS

Although an increase in venous pressure in the legs has been clearly demonstrated in all relevant reports, most workers have found no significant change in the upper extremities. The cen6

tral venous pressure reflects the degree of caval obstruction in the various body positions. Investigations by the ultrasonic flow detector method in various body positions in all stages of pregnancy and in the postpartum period brought clear evidence of obstruction to venous return from the lower extremities throughout pregnancy.” The venous obstruction was found to be more pronounced on standing than in the supine position. The raised venous pressure in the lower extremities is a positive factor in the development of peripheral edema and varicosities. CIRCULATION TIME

Measurements of the circulation time during pregnancy by the photoelectric method showed a decrease to about 17 seconds, as compared with an average of 23 seconds in a nonpregnant control group.12 However, other authors have pointed out that there is a considerable individual variation.3 SUPINE HYP~TENSIVE SYNDROME

The physiologic fall in cardiac output in late pregnancy in the supine position due to caval obstruction by the gravid uterus is not usually accompanied by a decrease in blood pressure or in heart rate, because of the countermanding effect of a concomitant rise in peripheral vascular resistance. However, some women react to the fall in blood pressure in the form of an accentuated parasympathetic response with bradycardia and no rise in vascular resistance. This sequence of events is likely to lead to a further fall in cardiac output and to syncope.’ A well-developed collateral venous circulation can compensate to some extent for the diminished venous return. Pregnant women prone to syncope should be advised to avoid the supine position for any length of time. PERIPHERAL EDEMA AND FLUID BALANCE

A significant proportion of normal women, possibly up to 50%, develop ankle edema in the course of pregnancy.3 The average woman accumulates about 8.5 L of water during a normal pregnancy and, understandably, there is a close relationship between the gain in body water and the extent of peripheral edema.13 The retention of water is mainly due to salt retention. It has been estimated that a pregnant woman under physiologic conditions accumulates up to 600 mM of exchangeable sodium.14 Although some of the women with peripheral edema who have 7

no evidence of cardiac or renal disease develop hypertension in the course of pregnancy, the presence of edema in early pregnancy cannot be regarded as an indication that hypertension is likely to deveop in the later stages of pregnancy.

CLINICAL, RADIOLOGIC HEART AND CARDIAC

AND ECG CHANGES PERFORMANCE

IN THE

The significance of the clinical, radiologic and ECG changes that occur as a rule in pregnant women in the absence of a cardiovascular disease lies in the fact that these changes may simulate organic heart disease. In difficult cases the problem is compounded by the understandable reluctance to resort to invasive investigatory methods. However, this disadvantage has been greatly mitigated in recent years by the diagnostic potentialities of echocardiography, which is as a noninvasive method eminently suitable to use in single or serial examinations during pregnancy. CLINICAL FEATURES, -There is usually a full pulse. It may be occasionally collapsing in character and associated with capillary pulsation, similar to the findings in aortic regurgitation. The apex beat is displaced upward because of the horizontal position of the heart and it is rather diffuse. The jugular veins can appear somewhat distended. The first heart sound is often accentuated, with occasional splitting. The second heart sound in the pulmonary area is also often increased. A common finding is a third heart sound, best heard at the apex in early diastole. Phonocardiographic examinations have detected a fourth heart sound in 16% of normal pregnant women.15 A short midsystolic ejection murmur is common; it is best heard in the apical and/or pulmonary areas and is probably produced by the increased blood volume and blood flow. On rare occasions, an early diastolic murmur is audible, considered to be originating from the tricuspid or mitral valve as a manifestation of increased blood flow.15 Extracardiac murmurs are also known to occur, systolic as a rule but occasionally continuing into diastole; these originate in the vessels of the anterior chest wall.

A. O’ROURKE: A diastolic murmur usually indicates underlying cardiac disease and would be an unusual finding due to pregnancy per se. Frequently, a third heart sound or the diastolic component of a continuous murmur is misinterpreted as a diastolic murmur. A cervical venous hum is present in most pregnant patients and, if transmitted to the upper thorax, may simulate a diastolic murmur of intracardiac origin. A prominent diastolic component of the mammary souffle may produce similar confusion. ROBERT

In the context of changes in cardiac murmurs in normal pregnant women, it should also be noted that the circulatory dynam8

its peculiar to pregnancy can also modify murmurs caused by organic valve disease. The diagnostic diastolic murmur of aortic regurgitation and the systolic murmur of mitral regurgitation can decrease in intensity or even become inaudible, possibly because of the decrease in peripheral vascular resistance.16 On the other hand, sympathomimetic drugs can increase the intensity of these murmurs just as they do in the nonpregnant state. ROBERT A. O'ROURKE: Near maximum handgrip exercise which increases

the systemic vascular resistance is a useful technique for increasing the intensity of aortic and mitral regurgitant murmurs in pregnant patients. as does intravenous DhenvleDhrine. RADIOLOGIC CHANGES. -As pregnancy advances, the heart assumes a horizontal position, which may be reflected radiologically by an apparent increase in the heart shadow. The cardiothoracic ratio may exceed 50%. The straightening of the left upper cardiac border and the apparent enlargement of the left atria1 shadow in the right oblique or lateral view may simulate the appearance of mitral stenosis. The hilar vascular markings become more prominent and may give rise to misinterpretation.

ECG CHANGES. -The change in the anatomical position of the heart results in a change in the QRS pattern. There is a gradual shift of the electrical axis to the left. A Q-wave in lead III that fully disappears on deep inspiration may persist in some women until after delivery. It is significant that a deep Q3 is often unaccompanied by a Q-wave in lead aVF. The frequent negativity of T, becomes less pronounced in deep inspiration and, at times, T, may become positive (Fig 1). Transient ST-segment depression and T-wave changes similar to those seen in cardiac ischemia are occasionally observed.17-1g These changes can be entirely related to the pregnant state as we have found that T-wave inversion can recur in the same patient in subsequent pregnancies. Prolongation of atrioventricular (AV) conduction occurs occasionally in the absence of any detectable cause. Partial AV block with Wenckebach periods has also been observed in the absence of organic heart disease. Intraventricular conduction is hardly ever affected. Ectopic activity in the form of isolated supraventricular and ventricular extrasystoles is not uncommon and, occasionally, extrasystolic bigeminy is present. Many workers believe that pregnancy increases the susceptibility to paroxysmal supraventricular tachycardia. CARDIAC PERFORMANCE. -There is an increased load on the heart in pregnancy. The increase in left ventricular work is directly proportional to the magnitude of the cardiac output as there is no rise in the mean arterial blood pressure. Studies of left ventricular function at various stages of pregnancy by non9

Fig l.-ECG tem. Inverted

in a 22-year-old T-waves in lead

pregnant 3 become

woman positive

with normal cardiovascular in deep inspiration.

sys-

invasive methods have provided interesting data, although some of the findings are at variance. Measurements of systolic time intervals20-22 have shown that the preejection period is shortened in early and midpregnancy. The left ventricular ejection time is usually prolonged at these stages. In the later stages of pregnancy, the preejection period becomes prolonged and there is progressive shortening of the left ventricular ejection time. The degree of prolongation of the preejection period is related to body position, i.e., it is less pronounced in the lateral recumbent than in the supine position. The preejection period can remain prolonged after delivery at a time when the cardiac output has already regained the pregravidic level. Echocardiographic studies23, 24 have suggested that the right and left ventricular end-diastolic dimensions are greater during 10

pregnancy than in the nonpregnant state, which is an expression of increased volume overload in pregnancy. End-systolic dimensions were found to be the same in pregnant and nonpregnant women. The velocity of circumferential fiber shortening, which reflects myocardial contractility, was found to be increased not only in the first half of pregnancy but also in its later stages. These findings can be interpreted as indicative of increased myocardial contractility in the first half of pregnancy, which is possibly a response of adaptation to volume overload. The data relating to the late stages of pregnancy are more difficult to evaluate, but there is some suggestion that myocardial contractility may be depressed at this stage, especially in the supine position, possibly due to a decrease in left ventricular preload. In the clinical context, myocardial depression in late pregnancy is unlikely to result in overt cardiac insufficiency in healthy persons. However, it is a matter of conjecture whether it can enhance the onset of myocardial failure in patients with preexisting organic heart disease or in those who are destined to develop peripartum cardiomyopathy. ROBERTA. O'ROURKE:If one considers the effects of alterations in preload, afterload and heart rate on isovolumic and ejection phase indices of left ventricular performance, there is NO evidence of a depression in myocardial contractility during any phase of pregnancy in healthy patients. MECHANISMS OF THE CARDIOCIRCULATORY CHANGES The various mechanisms responsible for the changes in the heart and circulation during pregnancy have not yet been fully clarified. However, important data have been accumulated in many clinical and research centers over the years, which throw light on many aspects of the problem. Evaluation of the findings suggests that the hemodynamic changes of “adaptation” are not designed entirely for the purpose of covering the metabolic needs of the fetus, as the maternal cardiac output is already significantly increased at a stage of pregnancy when the fetus is still quite small and has limited metabolic requirements.12 2 The original hypothesis that the placenta functions as an arteriovenous fistula and produces a uterine vascular system with low resistance explains many but not all the hemodynamic events.9 The greatest increase in cardiac output takes place when the placental vascular system is still in its early stages of development and it is now believed that the uterine hyperemia of early pregnancy has a hormonal basis.6 There is indeed unmistakable evidence that hormonal changes play a fundamental role in the production of the cardiocirculatory events peculiar to pregnancy. The circulatory state, with its specific changes, observed in human pregnancy has been reproduced in the ewe by the 11

THE MECHANISM OF THE CIRCULATORY

oestrogens

--

CHANGES IN PREGNANCY

increased myocardial contractility

-/

output

1 sodium and water retention

+

4 renin and aldosterone activity

Fig nancy.

2.-Various

4 increased blo volume r prolactin

factors

involved

in the

circulatory

changes

in normal

preg-

administration of estrogens.2 Increased estrogen levels and also progesterone promote sodium and water retention, which is also enhanced directly or indirectly by the raised plasma renin and aldosterone activity.2 Sodium and water retention causes an increase in plasma volume. There is experimental evidence that prolactin - a protein hormone produced by the anterior pituitary gland that increases in concentration from early pregnancycan also be a factor in increasing the blood volume.2 It has been postulated that estrogens also exert a positive inotropic effect on the heart muscle and promote myocardial contractility by influencing the actomyosin-adenosine tripophosphatase relationship.25 Increased myocardial contractility in the presence of low peripheral vascular resistance is an important factor in the increase in stroke volume and cardiac output in the earlier stages of pregnancy. Hypervolemia, the other important factor responsible for the increase in cardiac output, plays an increasing role in the later stages of pregnancy. The various factors involved in the circulatory changes in normal pregnancy are shown in Figure 2. RESPIRATORY

SYSTEM

A significant proportion of women who have no cardiorespiratory disease experience shortness of breath during pregnancy. The number of women complaining of dyspnea steadily increases as pregnancy advances and by the 30th week of gestation 76% of healthy women are found to be dyspneic.26 The cause of the dyspnea is basically physiologic and has a hormonal rather than a mechanical basis. Maternal hyperventilation results in a lowering of the alveolar carbon dioxide tension from 40 to 30 mm Hg or even less, as a process of adaptation meant to give the fetus an appropriate carbon dioxide transport system.3 The comparatively low maternal alveolar carbon dioxide tension is likely to be the main cause of the sensation of dyspnea. The vital capacity is either unchanged or slightly increased 12

with a decrease in expiratory reserve volume. The oxygen consumption rises progressively during pregnancy up to about 20% above the nonpregnant level. Respiratory embarrassment arising from the physiologic adaptive processes require precise delineation in the presence of organic heart disease with or without symptomatology. CLINICAL DISEASE

ASPECTS OF HEART AND PREGNANCY

The cardiovascular problems encountered in pregnancy fall into 3 categories: (1) complications of diseases that had been present before pregnancy, notably rheumatic heart disease, congenital malformations and hypertensive vascular disorders; (2) diseases that appear during pregnancy and have some causal relationship to it, such as peripartum cardiomyopathy, dissecting aortic aneurysm and pregnancy-induced hypertension (toxemia of pregnancy); and (3) disorders that occur during pregnancy but without any causal relationship to it and just happen to develop at that time. The great majority of patients are in the first category. In these situations, pregnancy can be regarded as a transient physiologic condition, admittedly with hemodynamic implications, in the course of a chronic illness. It also follows that the quality of management and the course of the disease in the years preceding pregnancy have an important bearing on the potential risks presented by pregnancy. Maternal mortality has been steadily decreasing over the years, and to a variable extent this applies to all causes of maternal death. In the cardiovascular field, this favorable trend, which has been especially conspicuous since 1950, is due partly to the decline in the prevalence and severity of rheumatic heart disease (which used to account for up to 90% of all types of heart disease encountered in pregnancy), partly to improved medical management and partly to the introduction of palliative or corrective cardiac surgery, which has become feasible in many types of cardiac defect. The triennial reports of the Department of Health and Social Security of England and Wales on the confidential inquiries into maternal death covering the period 1952- 1975 clearly show the prevailing trend.27 The national reports also confirm individual experience that with acquired heart disease, women of high parity and in the later years of reproductive life are at special risk, and that the greatest risk presents itself after the 36th week of pregnancy. Maternal deaths from congenital heart disease have been recorded as a separate entity since 1961. During the period 1961- 1966 there were 111 maternal deaths from acquired heart disease and 20 from congenital heart disease. By comparison, 49 and 13 maternal deaths, respectively, were recorded in 13

1970- 1975. Of the 49 deaths in the group of acquired heart disease, 19 were due to rheumatic heart disease, 10 to bacterial endocarditis, 9 to coronary disease and 11 to other conditions, including cardiomyopathies. In the congenital group, the 13 maternal deaths were due to Eisenmenger’s disease (21, patent ductus arteriosus (21, atria1 septal defect (31, ventricular septal defect (21, coarctation of the aorta (11, and nonspecified defects (3). ASSESSMENT OF THE CARDIAC OF ANTENATAL CARE

STATE

AND THE PRINCIPLES

Although a full history with identification of the salient symptoms is most desirable, assessment of the cardiac state should be based mainly, if not entirely, on objective signs. Experience has shown that in a variety of cardiac disorders, symptoms do not necessarily reflect the severity of the cardiac defect. A purely functional classification, which refers only to symptoms, is misleading and can be potentially dangerous. The original functional grades devised by the New York Heart Association, which also referred only to symptoms, have now been modified in order to take account of objective signs. This concept is best illustrated in mitral stenosis. Maternal death has occurred more often in patients who had been symptom-free in the early stages of pregnancy and later developed fatal pulmonary edema than in those with more advanced rheumatic heart disease accompanied by even more severe symptoms. Patients with past or present congestive heart failure, being less prone to episodes of frank pulmonary edema, usually respond satisfactorily to appropriate medical therapy and their pregnancy can be brought to a successful end. It is, therefore, in the younger, symptom-free patient with moderate-to-severe mitral stenosis in sinus rhythm-the most frequent type of cardiac defect encountered in pregnancythat purely functional prognostic grading may be dangerously misleading. In rheumatic heart disease, careful clinical examination, ECG examination and simple laboratory tests, as well as a chest xray study after the 1st trimester, will prove to be sufficiently informative in most cases. Except in a very special case, there is no justification, or indeed need, to resort to invasive methods of investigation, such as cardiac catheterization. However, echocardiographic examination is noninvasive and harmless in pregnancy and can provide useful additional information. In congenital heart disease, data obtained by cardiac catheterization and angiography may be essential for a precise diagnosis at this stage. Nevertheless in practice, today, most of these patients will have been already fully investigated in childhood and many will have already undergone surgical correction of the defect before reaching the childbearing age. After the initial assessment, continuing cardiac care is imper14

ative in order to detect complications in their early stages, especially incipient pulmonary congestation, disorders of cardiac rhythm and pregnancy-related increase in blood pressure. The frequency of routine attendances depends on the nature and severity of the underlying disease. However, patients should be seen at least at 4-week intervals, if not more frequently. All patients, including those who are well and show no impairment of cardiac function, should receive general advice regarding activity and regular rest, dietary measures and the importance of seeking medical advice without delay in case of a respiratory infection. If a patient fails to keep her appointment, it is desirable to find out why within the shortest possible time. This can be readily achieved with the help of the patient’s family doctor and/or a medical social worker. Cardiac antenatal care is indeed a team work requiring the closest collaboration between medical and obstetric staff.** In spite of recent reports to the contrary, we believe that routine iron therapy is advisable and we prefer the combined use of iron and folic acid. Although the fall in hemoglobin level is in many instances merely a sign of hemodilution in the presence of a physiologic increase in plasma volume, there are many patients who will derive benefit from prophylactic iron and folate supplements. It is unlikely that the comparatively short-term administration of iron can lead to excess deposition in the bone marrow. Should significant anemia develop, it can embarrass the circulation and it should be promptly corrected. If intravenous administration of blood is desirable, it should be given as packed cells in order to avoid sudden overloading of the circulation. A reduced sodium intake is desirable in view of the tendency to fluid retention. Regular weighing of the patient is necessary for the early detection of undue fluid retention. Current opinion favors the idea that the rather free use of diuretics in pregnancy should be discouraged, unless there is excessive fluid retention. Besides assessment of the cardiac state and function, the patient’s physical environment and her social and emotional problems are important considerations. To this end, a medical social worker can act as a useful link between the hospital clinic on the one hand and the patient and general practitioner on the other. The medical social worker plays an important role in the continuous community health service by assessing the patient’s home conditions as a whole, the husband’s ability to help and the feasibility of regular rest periods. She can also ensure that the prescribed regimen, including drug therapy, is followed consistently. Awareness of the significance of transplacental transmission of drugs administered to the mother forms an integral part of safe antenatal care. Most drugs cross the placental circulation. Special care should be taken during the 1st trimester, when 15

organogenesis takes place, and also in late pregnancy and labor. The use of cardiovascular drugs in pregnancy, with special reference to their transplacental transmission, is discussed in a separate section. The same section deals with the adverse effects of smoking and of alcohol consumption by the mother. The practice of admitting patients with severe heart disease to hospital 2 weeks or so prior to the expected date of delivery seems to be sound, even if their cardiac condition is entirely satisfactory. The purpose of this policy is to ensure that the patient is kept under close supervision near term and that she starts labor in a fully compensated condition. Using such a regimen, we have not encountered a single patient who developed heart failure during labor. Admittedly, unexpected episodes of tachyarrhythmia occurring at this stage have to be corrected as a matter of urgency in order to prevent the development of heart failure. The principles of obstetric management in patients with heart disease do not differ from those accepted in general obstetric practice in normal women. Personal continuity in supervising patients in antenatal clinics is highly desirable. In addition to conventional clinical and laboratory measures, fetal monitoring by improved methods of ECG, cardiotocography and ultrasound examination have greatly contributed to advances in fetal medicine and have favorably influenced fetal morbidity and mortality. In general, vaginal delivery at term should be the preferred method, with use of the forceps when appropriate in order to shorten the 2d stage of labor. As a routine measure, premature induction of labor offers no advantage at all and runs the potential risk of infection. Induction of labor has a place, however, in cases of hypertensive vascular disease. Delivery by cesarean section should only be carried out if indicated on obstetric grounds and should be avoided as far as possible in the presence of heart failure. However, it should be pointed out that Metcalfe and Ueland6 have advocated more recently delivery by elective cesarean section in selected patients with severe cardiac disease. They have stated that during cesarean section under epidural anesthesia without the use of sympathomimetic drugs there is virtually a complete hemodynamic stability, with only a marginal rise in cardiac output. The importance of the quality of anesthesia cannot be overemphasized. Epidural anesthesia is now frequently practiced for vaginal delivery in patients with various cardiac disorders, including those with cyanotic congenital heart disease. However, special care has to be exercised in the latter group to prevent an excessive fall in arterial blood pressure. The effects of oxytocic drugs in the presence of heart disease is discussed in a separate section on the use of drugs in pregnancy. 16

HEART FAILURE Under the term “heart failure” we have included 3 conditions with distinct clinical manifestations, namely, pulmonary congestion, frank pulmonary edema and congestive heart failure. In many instances they may only represent different stages of the same process, but each form has specific pathophysiologic and clinical implications. In the short-term context of pregnancy, acute pulmonary edema is a far more serious event than congestive heart failure. In pure, or dominant, mitral stenosis- by far the most common valve defect found in pregnant women-pulmonary congestion and edema are basically due to mechanical circulatory obstruction at the level of the mitral valve complex and are not caused by myocardial failure. In the presence of such a circulatory obstruction, an adequate blood flow from the left atrium to the left ventricle can only be maintained by an increase in left atria1 pressure, which occurs readily if the left atrium is not unduly enlarged and its myocardium is not markedly affected. The rise in left atria1 pressure leads in turn to an increase in pulmonary venous and capillary pressures. The increase in blood volume in pregnancy results in a further rise in left atria1 pressure, and the physiologic tachycardia that shortens diastole exerts the same effect by retarding left atria1 emptying. Thus, the circulatory dynamics of pregnancy can transform an anatomically moderate stenosis into one that is functionally more severe. In this way the pregnant woman with mitral stenosis is particularly prone to pulmonary congestion and edema if she is in sinus rhythm with only slight left atria1 enlargement (Fig 3). In dominant mitral regurgitation there is an increased volume load on both the left atrium and left ventricle. In the absence of an obstruction to left ventricular filling, left atria1 and pulmonary venous pressures usually remain at near normal levels until the development of left ventricular failure, which tends to occur late in the natural course of the disease, and mostly, but not invariably, after the childbearing age. Similarly, in aortic regurgitation the increased volume load on the left ventricle results in left ventricular failure at a comparatively late stage of the disease. In acquired aortic stenosis, left ventricular failure, effort angina and syncope also tend to appear after the 4th decade of life. Heart failure, in any of the 3 forms, can appear at any stage of pregnancy. However, its incidence increases as pregnancy advances. In our experience, two thirds of the episodes of heart failure occurred in the 3d trimester and nearly half of these during the last 4 weeks of gestation. Because of the circulatory changes, the early puerperium is also a critical period, when heart failure can recur or even appear for the first time. The central point in antenatal care remains the prevention of 17

Fig 3.-Illustrative example of the type of patient particularly prone to acute pulmonary edema in pregnancy. Chest x-ray film shows only slight cardiac enlargement and increased pulmonary vascularity in a 24-year-old woman with mitral stenosis. She had been entirely symptom-free until the 38th week of pregnancy, when she suddenly developed frank pulmonary edema following an emotional upset.

heart failure by control of the immediate precipitating factors, among which respiratory infection, ectopic tachycardia and unusually severe physical effort are important events. Failing this, the recognition of early pulmonary congestion as the initial phase in the development of pulmonary edema and prompt therapeutic intervention are most rewarding factors of prevention of morbidity and mortality. The patient should be advised to rest in bed, preferably in hospital, under close supervision. She should be nursed in a semirecumbent position. Adequate sedation and sleep should be ensured. We believe that the institution of digitalis therapy at this stage is beneficial, even in the presence of sinus rhythm, and we prefer slow digitalization with appropriate adjustments of the dose to obtain the maximal therapeutic effect without inducing cardiotoxicity. It is important to prevent an electrolyte imbalance, especially a decrease in serum potassium levels, particularly if concomitant diuretic therapy is also recommended. Judicious salt restriction is desirable. If a respiratory infection is present, effective antibiotic therapy is indicated. For patients who have been taking oral penicillin as 18

antistreptococcal prophylaxis, other antibiotics should be prescribed. The overwhelming majority of patients will respond satisfactorily to the above regimen and cardiac surgery will not have to be considered at this stage. However, they should be advised to curtail their physical activity and have longer periods of rest than before. They should continue with maintenance digitalis therapy. Review of the cardiac condition becomes now advisable at weekly intervals during the remainder of the pregnancy. The development of acute pulmonary edema is still to be regarded as a most serious emergency. Due to significant advances in management, no case should end fatally today; however, until about 1960, pulmonary edema was the most important single cardiac cause of maternal death. The patient should be immediately hospitalized, if possible, in a conveyance with suitable resuscitation equipment. The immediate measures to be taken are administration of oxygen and establishment of clear airways, intravenous injection of morphine (10 - 20 mg, depending on the build of the patient and the urgency of the situation) and intravenous injection of a rapidly acting diuretic in an adequate dosage. Morphine helps not only by relieving anxiety and slowing the respiratory rate but also by dilating the peripheral veins and thus reducing venous return. The use of digitalis is controversial in this situation in sinus rhythm, but we believe that there is a place for cautious digitalization which could be combined with a suitable /I-adrenergic blocking agent in low dosage in order to reduce the heart rate more expeditiously. Aminophylline is mainly beneficial in cases with associated bronchospasm. Through all these procedures the patient should be kept continuously in a semirecumbent position, which reduces the intrathoracic blood volume. If the above measures do not result in prompt improvement, endotracheal intubation with assisted respiration should be instituted without delay as a life-saving measure. At this stage, if not before, the suitability of the patient for cardiac surgery should be ascertained. In practice, it is most likely that the patient will have moderate-to-severe pure or dominant mitral stenosis and will be suitable for closed mitral valvotomy. However, should valve replacement prove necessary on account of significant mitral regurgitation and/or important aortic valve disease, open heart operation is feasible during pregnancy, although it carries a greater risk. The indications for closed and open heart surgery during pregnancy are fully discussed in a separate section. Right-sided heart failure secondary to left-sided heart failure is now hardly ever seen in pregnancy. Observations in the days when it was encountered more frequently showed that these patients were usually well over 30 years of age, with mitral and aortic valve involvement and with rather marked cardiac en19

largement. Atria1 fibrillation was not uncommon in this group. Most of these patients did not have close supervision in the early weeks or months of pregnancy. On the whole, they responded satisfactorily-to measures against heart failure when hospitalized and, under strict management, perhaps mainly in hospital during the remainder of pregnancy, had an uneventful labor and puerperium. This type of patient undoubtedly requires open heart surgery. Nevertheless, since she is likely to respond adequately to medical measures alone over a comparatively short period, it should be possible to defer cardiac surgery until a suitable time after delivery. The role of vasodilator therapy in the management of heart failure in pregnancy has not yet been evaluated. DISORDERS

OF THE CARDIAC

RHYTHM

Normal pregnant women display not infrequently transient disturbances of sinus node activity, such as wandering pacemaker and sinoatrial block. Junctional rhythm and extrasystoles, mainly supraventricular in type, are also common occurrences. Occasionally, both supraventricular and ventricular extrasystoles appear in the form of a bigeminal rhythm. Usually, patients are not conscious of these rhythm disturbances, but even if they are, no clinical significance should be attached to these changes and, apart from reassurance and possible sedation, no therapeutic action is required. Continuous monitoring during labor revealed frequent instances of sinus arrhythmia, wandering pacemaker junctional rhythm and premature beatszg The significant rhythm disturbances observed in pregnant patients are supraventricular arrhythmias, namely, atria1 tachycardia, atria1 fibrillation and flutter, which occur mainly in association with rheumatic heart disease. There is suggestive evidence that pregnancy per se increases the susceptibility to paroxysmal atria1 tachycardia. It is possible that the increased blood volume may be a factor in determining the onset of atria1 fibrillation in patients with severe rheumatic heart disease by further distending an already large left atrium.9 In this context it is noteworthy that patients who develop atria1 fibrillation during pregnancy do so mainly after the blood volume has reached its maximal increase. Ventricular tachycardia occurs in pregnancy only on rare occasions. Acquired permanent complete heart block is also rare, but transient partial heart block (2d degree) has been occasionally observed as a manifestation of active rheumatic carditis. Prolonged P-R interval (1st degree) is a common finding, but it does not necessarily indicate an active rheumatic process and in many instances the prolonged AV conduction has been induced by digitalis administration. When atrial tuchycardia is associated with rheumatic heart disease, the underlying valve defect in the great majority of cases 20

is mitral stenosis. Dominant mitral regurgitation is found much less commonly. Atria1 tachycardia is an uncommon complication of pure aortic valve disease that can occur at any stage in the evolution of mitral stenosis and bears no close relationship to the severity of the valve defect or the extent of myocardial pathology. Similarly, there is no correlation between the appearance and frequency of the attacks and the cardiac size. The main significance of paroxysmal atria1 tachycardia lies in the potential risk of heart failure precipitated by the rapid ventricular rate. This risk seems to be greater in pregnancy than in the nonpregnant state. The development of heart failure is closely related to the duration of the attack. In our experience, none of the attacks that ceased spontaneously or were controlled therapeutically within a few hours resulted in heart failure. On the other hand, rather prolonged attacks precipitated heart failure on several occasions.1s It is perhaps noteworthy that 12 of the 28 patients with documented episodes of paroxysmal atria1 tachycardia had attacks only during one or more pregnancies and were free from attacks without receiving antiarrhythmic medication in the nonpregnant state over a follow-up period averaging 10 years. Paroxysmal atria1 tachycardia can be often terminated by carotid sinus pressure. However, caution and careful monitoring of the procedure are recommended, because ventricular arrhythmias can occur at times immediately after cessation of the tachycardia. If this method proves unsuccessful, a p-adrenergic agent, Verapamil or any of the conventional antiarrhythmic drugs can be given as their use is not contraindicated in pregnancy. In case of an already prolonged attack, direct current shock therapy is probably the preferred method; it is safe in pregnancy as it is known to have no deleterious effect on the fetus. Caution should be exercised in digitalis-induced atrial tachycardia with a 2:l AV block, because direct current shock may potentiate digitalis cardiotoxicity. Diphenylhydantoin has been found especially effective in digitalis-induced tachycardia. In the event of frequent recurrences of atria1 tachycardia, a regimen of prophylaxis should be considered, using one of the conventional antiarrhythmic drugs, including quinidine. The use of oral quinidine has been discouraged in several centers. Yet, in others, including our own, slow-release quinidine with regular estimations of the serum quinidine level and with due attention to dosage of concomitant digitalis therapy, if any, has been found effective and safe in the prevention of recurrences. In a number of reported instances of cardiotoxicity attributed to quinidine, the case histories suggest that digitalis was in fact responsible for the adverse effects. There is indeed recent evidence of digoxin-quinidine interaction manifesting itself by an increase in serum digoxin concentration in patients given quini21

dine who were already receiving digitalis.30 The judicious use of quinidine is feasible in pregnancy, except in the early and late stages. In prophylactic doses, it does not affect the uterine musculature until the uterus has reached the stage of natural initial contractions. A. O’ROURKE: As a general rule, the dosage of oral digoxin necessary to produce a given serum level is reduced to 50% when coincident quinidine therapy is instituted.

ROBERT

Atria1 fibrillation that becomes established in the presence of rheumatic heart disease usually indicates an advanced stage in the natural course of the disease. In general, atria1 fibrillation carries an increased risk of heart failure and thromboembolism. The risk of these complications is even greater in pregnancy than in the nonpregnant state. Both heart failure and embolism are especially liable to occur early after the onset of atria1 fibrillation. The underlying valve defect is predominantly mitral stenosis and/or mitral regurgitation. Pure aortic valve disease is uncommonly associated with atria1 fibrillation. Until a few decades ago, pregnancy complicated by atria1 fibrillation was justifiably regarded as a hazardous combination. A summary of data from several centers revealed a heart failure rate of 52%, a maternal mortality of 17% and a fetal loss of 50%.3l During the past 2 or 3 decades there has been a most favorable change in this situation. Of more than 1,000 pregnancies associated with rheumatic heart disease that we have studied over 3 decades, 6.5% were complicated by atria1 fibrillation. In nearly half of the cases, atria1 fibrillation appeared for the first time during pregnancy.lg The diminishing frequency of atria1 fibrillation observed in pregnant women in recent years is probably due to the decreasing severity of valvar and myocardial involvement, in addition to the falling incidence of rheumatic heart disease. The onset of atria1 fibrillation during pregnancy constitutes an emergency and should be regarded as such. The patient should be admitted to hospital at once. The first priority is to reduce the ventricular rate, which is invariably unduly high in this situation in a previously undigitalized patient. This can be expeditiously achieved by correct oral digitalization, possibly combined with a suitable /3-adrenergic blocking agent. If pulmonary congestion has already developed, additional diuretic therapy should be introduced. Any electrolyte imbalance, especially a low serum level of potassium, should be speedily corrected. In view of the increased risk of systemic embolism, the institution of anticoagulant therapy should be considered. The use of anticoagulants in pregnancy is discussed in the section on thromboembolic disease. After control of the ventricular rate 22

and stabilization of the clinical condition, an early decision should be reached regarding the advisability of restoring normal rhythm. To this end direct current shock therapy is preferable to the use of antidysrhythmic drugs. If the dominant valve lesion is mitral stenosis and the atria1 fibrillation is not long-standing, there is a 90% chance of restoring sinus rhythm and a reasonably good expectation of being able to maintain it in a fair number of patients for a considerable time, under closely supervised antiarrhythmic prophylaxis. After atria1 defibrillation, the patient should be advised to continue the regimen of adequate rest and should be seen at weekly intervals after discharge from hospital. The dosage of maintenance therapy should be promptly adjusted according to the findings and requirements. Whether treatment with anticoagulants is continued and for how long are matters of clinical judgment in the individual case. If an attempt at atria1 defibrillation is unsuccessful, control of the ventricular rate and the measures against heart failure remain imperative. In this case, we believe that there is a strong indication to continue therapy with anticoagulants. Atrial flutter is uncommonly observed in pregnancy. Its clinical significance is in many respects similar to that of atria1 fibrillation. If the ventricular rate is fast, as it usually is in rheumatic heart disease in undigitalized patients, appropriate antiarrhythmic therapy is urgent. The application of direct current shock is the preferred method because it abolishes atrial flutter and restores sinus rhythm in virtually 100% of the cases. Ventricular tachycardia is only rarely found in pregnant women and hardly ever in the presence of rheumatic heart disease. Continuous electromagnetic tape recording of the ECG during labor revealed an episode of ventricular tachycardia in a previously asymptomatic woman with rheumatic heart disease.32 However, the abnormal rhythm appeared a few minutes after the administration of nitrous oxide and cyclopropane and was probably related to the induction of anesthesia. Should ventricular tachycardia appear during pregnancy, intravenous lidoCaine should be used to terminate the attack. If this fails, the application of direct current shock would be the preferred method of therapy, except perhaps in digitalis-induced ventricular tachycardia. Oral antiarrhythmic agents may be required to prevent recurrence. In cases that prove to be unmanageable by conventional methods, artificial pacing can be effective in controlling ectopic tachycardia. Wolff-Parkinson-White syndrome is frequently encountered in general cardiologic practice. We have seen this combination only in one pregnant patient. The episodes of ectopic tachycardia should be treated in the usual way, but digitalis should be avoided in the presence of complicating atria1 fibrillation. 23

INFECTIVE ENDOCARDITIS

Due to the changing clinical pattern of the disease, the presenting symptoms and signs of infective endocarditis may be variable, making an early diagnosis difficult at times. This is especially true in pregnancy. Furthermore, even repeated blood cultures may not yield a positive result in a number of instances. In the experience of Hayward,33 in 30% of the cases with diagnostic clinical features, blood cultures were repeatedly negative. Before the antibiotic era, infective endocarditis was mainly observed in the puerperium, but cases occurring during the antenatal period were by no means rare and mortality was rather high. This appears paradoxical since infective endocarditis is more common in men and it is generally uncommon in pure mitral stenosis, which is by far the most common valve defect encountered in pregnancy. The introduction of chemotherapy changed the situation. In 1958, Burwell and Metcalfeg stated that bacterial endocarditis was a disappearing disease in pregnancy. Currently, infective endocarditis still occurs in pregnancy and it is observed during the antenatal period rather than in the puerperium. Furthermore, patients with valve prosthesis are prone to infective endocarditis caused at times by unusual organisms, not necessarily bacterial in nature. It is only on rare occasions that a normal valve is affected. In rheumatic heart disease, the underlying valve defect is mainly pure or dominant mitral regurgitation (which is mild rather than severe) and less commonly, aortic regurgitation. The cardiac rhythm is usually normal. Although infective endocarditis is not as rare in atria1 fibrillation as has been generally believed, this combination is mainly found in an older age group. ROBERT A. O'ROURKE: In patients with mitral regurgitation

who develop infective endocarditis during pregnancy, the mitral regurgitation is more likely due to the mitral prolapse syndrome than to rheumatic heart disease.

In cases with a positive blood culture, the main causative organisms are the P-hemolytic Streptococcus, Pneumococcus and Staphylococcus aureus in the rather acute form of the disease, and Streptococcus viridans in the subacute form. In recent years, unusual organisms have been cultured more frequently, even in patients who have not had previous valve replacement. Death is mainly due to progressive heart failure and occasionally to persistence of the infection. Even if the infection seems to have been brought under control, heart failure can still develop and progress because of extensive myocardial damage.34 Rupture of a valve can cause acute heart failure and death. A more recent report on bacterial endocarditis in pregnancy 24

reiterated the still considerable risk of heart failure and maternal death, but mainly as a result of delay in diagnosis and treatment.35 Thus, infective endocarditis occurring in pregnancy should still be regarded as a most serious complication. However, considering the currently available modalities of adequate management, it should not constitute an indication for termination of the pregnancy. Admittedly, early diagnosis and treatment are essential for a successful outcome. It is obvious that it is most helpful to obtain a positive blood culture, but it is equally important that the lack of it should not lead to a delay in instituting vigorous treatment, if the clinical signs are sufficiently suggestive. In the treatment of infective endocarditis a combination of antibiotics may be preferable to the use of one single drug, especially in the presence of negative blood cultures. In this situation, large doses of penicillin with streptomycin or gentamicin constitute .a reasonable combination, but one should be ready to use other combinations, like vancomycin and cephaloridine. The duration of active treatment is an important consideration. In principle, the conduct of management (including the choice of drugs) in pregnancy does not differ from that adhered to in the nonpregnant state.36, 37 For cases in which no speedy improvement occurs and there is a threat of progressive heart failure, current opinion favors early surgical intervention. In certain cases, valve replacement should be considered even before the contemplated course of antibiotic treatment is completed. A similar approach is to be adopted in pregnancy, should such a problem arise.35 Infective endocarditis is in many instances a preventable complication and due attention should be given to this point in the management of susceptible patients in pregnancy as well as in the nonpregnant state. Patients at risk should be enlightened regarding the importance of not neglecting trivial injuries and skin or throat infections. Antibiotic prophylaxis is mandatory at the time of dental manipulations or oral surgery in general, and may be desirable during some instrumentations and other surgical interventions. It is not feasible to formulate clear recommendations for all clinical situations; the indications for antibiotic prophylaxis in general, the choice of antibiotic and the method of administration must remain a matter of clinical judgment in the individual patient.38 It should be reemphasized that in a patient with rheumatic heart disease who has been on continuous antistreptococcal prophylaxis by penicillin, an antibiotic other than penicillin should be used for antibacterial purposes to circumvent the possibility of penicillin-resistance. The need for routine antibacterial cover of childbirth has been questioned recently. Although we accept that the risk of infective endocarditis developing during labor or in the puerperium is currently small, we still believe that the institution of anti25

biotic cover is justifiable from the onset of labor to the 6th or 7th postpartum day. An important study from the laboratory of the Boston Lying-In Hospital showed that in a series of 74 blood cultures taken a$ various intervals during labor and after delivery in 17 pregnant women, not a single instance of bacteremia was found; this confirms only the rarity of infection at this time, but not its nonexistence.g The authors themselves believed that these observations were only reassuring, but not decisive enough to justify discontinuing the policy of giving prophylactic antibiotics during childbirth. The issue is that the use of antibiotics over such a short period is virtually harmless and there are several instances in medical practice, especially in preventive medicine, that justify the pursuit of a general policy that can only benefit a small proportion of the people involved. Infective endocarditis occurring in patients with congenital heart disease, another important group especially liable to develop infection, is discussed within the framework of specific congenital cardiac malformations. RHEUMATIC

HEART

DISEASE

THE CHANGING PATTERN OF ACUTE AND CHRONIC RHEUMATIC HEART DISEASE

There has been a significant decrease in the prevalence of acute rheumatic fever and carditis in Western countries during the past 2 decades. An even more striking feature has been the decline in the severity of the disease; as shown by clinical experience, a residual valve lesion following the acute episode of carditis has been observed in recent years less frequently than in the past. Furthermore, the residual valve lesion is now often mild, characterized in most cases mainly by an apical systolic murmur, with little or no cardiac enlargement. This changing pattern is likely to be due to a decline in the virulence of Streptococcus and possibly also to a change in host susceptibility. On the other hand, the insidious development of pure mitral stenosis without a history of an overt rheumatic episode is still a relatively common event. Accordingly, the prevalence of chronic rheumatic heart disease will have to be determined in the future by routine mass examination of various well-defined sections of the population rather than by the follow-up of known cases of overt acute rheumatic carditis, as has already been suggested by Besterman.3g This favorable change in the incidence and severity of rheumatic carditis has resulted in a decrease in the number of patients with chronic rheumatic heart disease found in antenatal clinics. Another result is the decline in the severity of complications occurring in pregnancy. The situation is different in Eastern countries and in some parts of Africa, where acute 26

rheumatic sufficiently problem.

fever and chronic rheumatic heart disease are still frequent and severe to constitute a major health

ACUTE RHEUMATIC MANIFESTATIONS IN PREGNANCY

Initial episodes of all 3 major clinical manifestations of acute rheumatic fever, namely, polyarthritis, chorea and carditis, have become rare occurrences in pregnancy. Recurrences are occasionally observed among those patients who have not received antistreptococcal prophylaxis and who had a previous episode within 1 or 2 years prior to pregnancy. The clinical features of an acute attack may be obscured, because the endocrine changes of pregnancy may modify some of the signs of the disease.40 In this context it is of interest that rheumatic activity has been observed comparatively more frequently in the early puerperium, when it could be considered to represent a rebound phenomenon.9, lg In the management of active rheumatism, diagnosis and subsequent eradication of streptococcal infection are imperative. In addition to administration of salicylates, the judicious use of steroids should be considered during pregnancy in cases of severe carditis, but special care should be exercised because of the possibility of adverse effects on the fetus.41, 42 INCIDENCE OF CHRONIC RHEUMATIC HEART DISEASE IN PREGNANCY

Between 1940 and 1960, studies in the U.S. and the United Kingdom reported that up to 4% of pregnancies were complicated by heart disease and up to about 90% of all types of heart disease found in pregnant patients were rheumatic in origin. During the past 2 decades a significant decrease has been observed in the incidence of rheumatic heart disease among pregnant patients. In recent years, rheumatic heart disease has constituted less than 80% of all types of heart disease seen in antenatal clinics.g, lg, 31,43 The proportion of rheumatic cases is progressively diminishing. MAIN COMPLICATIONS OF RHEUMATIC HEART DISEASE AND THEIR MANAGEMENT

Most patients with established rheumatic valve defects, including a number at an advanced stage of the disease, tolerate the hemodynamic burden of pregnancy well and have an uneventful course. On the other hand, a small proportion of the patients, not all necessarily with advanced disease, have one or more serious complications, namely, heart failure, atria1 tachyarrhythmias, thromboembolic manifestations or infective endo27

carditis. Due to improved medical treatment and to better and earlier selection of patients for cardiac surgery and also as a result of the natural decline in the severity of the disease, all these complications have occurred less frequently in recent years. Nevertheless, they remain serious and in some instances life-threatening and therefore demand prompt therapeutic action. The onset of complications depends on a number of cardiac and primary extracardiac factors. The main cardiac factors are the nature of the dominant valve defect, the hemodynamic stage reached by the disease in its natural evolution and the presence or absence of clinical or subclinical rheumatic activity reflecting the myocardial factor. Of the primary extracardiac factors, infection and anemia are of particular importance. Respiratory infection can precipitate heart failure, and bacteremia can result in the development of infective endocarditis. Severe anemia adds to the circulatory load by leading to a further increase in heart rate and in cardiac output. CARDIAC SURGERY IN RHEUMATIC HEART DISEASE IN RELATION TO PREGNANCY

The great majority of pregnant patients with rheumatic heart disease can be successfully managed on medical lines alone, without cardiac surgery. Furthermore, the current position is that a good number of patients have already undergone surgical treatment before their first or subsequent pregnancy. Thus, there is only a small group left of surgically untreated patients who seem to require early valve surgery to alleviate morbidity; in a few of these, cardiac surgery can be justifiably regarded as a life-saving measure. In the individual pregnant patient, the decision has to be made whether combined medical and surgical treatment is preferable to medical management alone, deferring surgical treatment until a convenient time after delivery. This is a matter of clinical judgment based on careful analysis of all relevant factors, cardiac and noncardiac, since it is unlikely that each patient can be placed in one of the groups with clearly defined indications for early cardiac surgery. In this context, it can be stated today categorically that pregnancy per se does not increase the surgical risk as such. However, in the presence of postoperative complications, which have become much less frequent in recent years, the pregnant and nonpregnant states are not comparable. Closed cardiac surgery can be performed at any stage of pregnancy. The operation does not carry an increased risk of miscarriage. On the other hand, open heart operation is best delayed until after the 1st trimester. There is evidence that cardiopulmonary bypass may have a deleterious effect on the fetus if it is performed in early pregnancy, during the period of organogene28

sis. Considering the natural history of rheumatic heart disease, it cannot be too strongly emphasized that surgical treatment, however successful, cannot replace continued supervision and medical management during the remainder of pregnancy, and obviously thereafter. MITRAL VALVOTOMY DURING PREGNANCY.-In general,theindications for closed mitral valvotomy performed during pregnancy are virtually the same as those in the nonpregnant state. However, in certain situations, operative treatment would appear to be more urgent during pregnancy and in others it may seem advisable to postpone it until after delivery.44 In the early days of valve surgery, when the operative risk was significantly higher than the general maternal death rate, a rather cautious approach was taken to the question of advising closed valvotomy in the pregnant patient. That attitude has been gradually replaced by a more determined and confident decision making. Currently, in well-selected cases, closed mitral valvotomy carries an operative risk well below 1%. Admittedly, there is always a minimal potential risk that a well-planned closed valvotomy will lead, for technical reasons, to an open valvotomy or valve replacement. Critical analysis of the case histories reported in the literature (including our own) of patients who have undergone closed mitral valvotomy during pregnancy or in the early puerperium from the early days of mitral valvotomy to date,“, s, ls, 31 as well as course of events in a large group of “nonsurgical” pregnant patients reveals that closed mitral valvotomy is indicated today in 3 categories of pregnant patients with pure mitral stenosis. In the first category are patients who develop pulmonary congestion and show no prompt response to appropriate medical treatment. In the second group are cases of acute pulmonary edema, in which operative intervention should be regarded as most urgent. Understandably, it is advantageous to postpone surgery until after recovery from the acute attack, but in the exceptional case when pulmonary edema cannot be readily controlled by medical treatment, valve surgery should be undertaken as an emergency procedure. Profuse and uncontrollable hemoptysis constitutes the third indication. This can be a dangerous complication and may also require urgent valve surgery (Fig 4). In this situation, the mitral valve obstruction is invariably severe and is usually associated with pulmonary venous and arterial hypertension. Admittedly, the potential operative risk is higher in this group of patients, but in all reported cases, closed mitral valvotomy or mitral valve replacement performed either during pregnancy or in the nonpregnant state brought about an immediate cessation of hemoptysis and marked improvement in the patient’s condition.ls Our experience favors the view that profuse hemoptysis in mitral stenosis is, at least in pregnancy, not necessarily self-limiting. In a group of 30 patients in whom we 29

Fig 4.-Chest x-ray study of a 27-year-old pregnant woman with severe mitral stenosis and pulmonary hypertension. She developed profuse, uncontrollable hemoptysis toward the end of the 2d trimester. Closed mitral valvotomy at this state resulted in complete cessation of hemoptysis and an uneventful course of the remainder of pregnancy.

advised closed mitral valvotomy during pregnancy or in the puerperium, the preoperative cardiac status conformed in all to one of the categories discussed here. It cannot be too strongly stated that mitral valvotomy does not necessarily protect the patient entirely against further complications during the remainder of pregnancy. In our experience, 8 of 27 patients with preoperative sinus rhythm (29%) developed atria1 fibrillation postoperatively, but in 6 of these, sinus rhythm either returned spontaneously or was restored by therapeutic measures. It is perhaps noteworthy that the incidence of postoperative atria1 fibrillation was comparatively higher when mitral valvotomy was performed during pregnancy than in a large group of unselected patients who underwent closed mitral valvotomy in the nonpregnant state (16%). This difference may appear even more significant if we consider that the latter group included, on the whole, more advanced cases of rheumatic heart disease. Other postoperative complications included occasional transient heart failure and pulmonary or systemic embolism. However, many instances of postoperative complications are preventable and, indeed, such complications have occurred very much less frequently during the past decade or so. The only 30

maternal death in our group of 30 patients who underwent mitral valvotomy during.pregnancy or in the puerperium occurred in 1960. The patient was a 27-year old woman who developed intractable pulmonary edema at 38 weeks’ gestation. She had an emergency closed mitral valvotomy but did not regain consciousness after operation and died 18 hours later. Perioperative cerebral embolization (confirmed by autopsy) may have been the cause of death. Follow-up studies of patients who underwent mitral valvotomy during pregnancy and of those who were operated on in the nonpregnant state showed no difference in the long-term course of the disease.lg The effects of pregnancy, in general, on the longterm course of rheumatic heart disease will be discussed in a separate section. MITRAL VALVOTOMY AND SUBSEQUENT PREGNANCY. -Extensive experience has now been gained in various centers in the study of pregnancies subsequent to closed mitral valvotomy. Although there is general agreement that the course of pregnancy is significantly less complicated after successful valvotomy, there is ample evidence to substantiate the need for continued close supervision. In a study of 325 postvalvotomy pregnancies in 182 women there were 10 maternal deaths either in the antenatal period or in the puerperium.45 The cause of death was heart failure in 7 women and cerebral embolism in 3. In this series of cases, the development of atria1 fibrillation was of grave prognostic significance. In another study based on observations in 250 postvalvotomy pregnancies,46 there were 5 maternal deaths: 2 women died during pregnancy and 3 in the immediate postpartum period. In a personal study of 60 pregnancies subsequent to mitral valvotomy in 44 patients, 9 pregnancies (15%) were complicated by heart failure. One of these patients, who had had a mitral valvotomy in a previous pregnancy 3 years earlier, died during an episode of acute pulmonary edema. She had not been seen by a physician during this pregnancy until she was admitted to hospital with the acute attack of pulmonary edema. Three patients is this group required a second mitral valvotomy shortly after pregnancy. There was no close relationship between the incidence of heart failure and the time interval between valvotomy and subsequent pregnancy. Atria1 fibrillation was present in 11 of the 60 pregnancies (18%), but it developed during the pregnancy in question only in one instance; in the other 10 cases it had been already present before pregnancy. Four pregnancies were complicated by systemic embolism (6.6%): twice in atria1 fibrillation and on two occasions in sinus rhythm. Improvement in the functional capacity of the heart after mitral valvotomy in relation to pregnancy can be more reliably 31

assessed by comparing the course of pre- and postvalvotomy pregnancies in the same patient. We were able to do this in 22 patients who had 34 prevalvotomy and 28 postvalvotomy pregnancies. ThGncidence of heart failure was 44% in the former group and 18% in the latter group, in spite of the fact that all patients in the prevalvotomy pregnancy group maintained sinus rhythm persistently, whereas 16% of the postvalvotomy pregnancies were complicated by atria1 fibrillation. In some centers, mitral valvotomy is performed preferably as an open heart operation, even in cases of first valvotomy. Such procedures have been carried out during pregnancy4’ and resulted in significant improvement in the condition of the mothers, but also in some miscarriages. The effects of cardiopulmonary bypass during pregnancy are discussed in the next section. VALVE REPLACEMENT DURING PREGNANCY.-Individual experience in valve replacement carried out during pregnancy must obviously remain limited. Pregnancy is not an ideal time to carry out such procedures and in practice there are only very few pregnant patients in whom valve replacement would have to be considered in any way. The operative risk is understandably greater than in closed cardiac surgery, but there is no confirmatory evidence that open heart surgery with cardiopulmonary bypass carries a greater risk to the pregnant than to the nonpregnant woman. On the other hand, the risk to the fetus is decidedly increased as shown in a review of 22 cases from various centers with various cardiac disorders.47 For this reason, valve replacement should only be considered during pregnancy in urgent and well-selected cases of intractable heart failure and preferably after the 1st trimester. Short perfusion times at high flow rates would provide the optimal placental perfusion and are likely to assure adequate oxygenation of the fetus.6, 47 On rare occasions an emergency situation may arise in which thrombotic occlusion of an existing valve prosthesis leaves no alternative to the urgent insertion of another valve as a lifesaving measure. This was the case in a recent report by Miller et a1.48 concerning a 35year-old woman. She developed cardiac failure at 6 weeks’ gestation and had a mitral valve replacement with a Bjork-Shiley prosthesis since it was not possible to do a closed mitral valvotomy because of heavy calcification of the valve. Anticoagulant therapy was instituted postoperatively. At term she developed chest pain and collapsed. Investigations revealed an obstructed mitral valve prosthesis and a second emergency mitral valve replacement was carried out. She went into labor 6 hours after operation and was delivered by forceps under epidural anesthesia. The mother made a complete recovery, but regrettably the child was found retarded at the follow-up examination at the age of 10 months. A 22-year-old woman whose case history was reported by McLeod et a1.4s had an emergency mitral valve replacement 3 weeks after delivery because of throm32

botic occlusion of a prosthetic Bjork-Shiley valve. She had been receiving low-dose subcutaneous heparin from the 17th week of pregnancy having been previously on oral anticoagulants. A 41year-old woman underwent mitral valve replacement in our Regional Cardiothoracic Centre at 26 weeks’ gestation because of deterioration of her cardiac condition culminating in an attack of pulmonary edema. She had had a closed mitral valvotomy 5 years previously. The remainder of her pregnancy was uncomplicated and she had a healthy infant.50 VALVE REPLACEMENT AND SUBSEQUENT PREGNANCY. -Experience in the management of pregnant patients with valve prosthesis is steadily increasing. In addition to the usual potential complications associated with rheumatic heart disease, some of which are even more likely to occur after valve replacement, mainly infective endocarditis and possibly thromboembolism, an important problem arises here concerning the use of anticoagulants. In an attempt to obviate the necessity of anticoagulant prophylaxis, several centers have advocated in recent years the use of biologic valves in young women who expect to become pregnant. On the whole, it is true that biologic valves decrease significantly the risk of embolism, but at the same time it is necessary to appreciate that the presence of atria1 fibrillation and the structural lesion of the left atrium and its size are factors to be considered in the pathogenesis of thromboembolism. Infective endocarditis of bacterial or fungal nature can occur in both prosthetic and biologic valves. An early report on pregnancy after prosthetic heart valves was that by Ueland et al. 51 It concerned 2 patients with StarrEdwards aortic valve prosthesis who had uncomplicated pregnancies. It is of interest that these two patients were not receiving anticoagulants at any stage of pregnancy. The subject was reviewed in 1971 by Buxbaum et al.,52 who summarized data from several centers relating to 50 pregnancies in 43 women with prosthetic heart valves. There was only one maternal death, but the fetal loss amounted to 28%, mainly due to bleeding complications and to the teratogenic effects of oral anticoagulants. On the other hand, when no anticoagulants were given to the mother, there was an increased risk of embolism. It is noteworthy that a higher incidence of embolism was found in those patients in whom anticoagulant therapy was discontinued during pregnancy than in the group of patients who did not receive anticoagulants at all. Other case reportP, 53-56have also stressed the hazard of systemic embolism in patients not given anticoagulants on the one hand and the risk to the fetus from the use of oral anticoagulants on the other hand. However, certain authors expressed the view that with strict control of anticoagulant treatment the risk of embolism can be significantly reduced and fetal salvage improved. 33

The cases of patients with prosthetic heart valves who become pregnant constitute today one of the most challenging cardiologic situations in obstetric practice. On the basis of collective experience it should be feasible to formulate tentative answers or guidelines regarding the approach to the more pressing problems. Termination of pregnancy is not a solution in these cases. Although heart failure was a significant antepartum complication in some of the patients, the general consensus is that the physiologic load of pregnancy is usually well tolerated. Except in patients with biologic valves, anticoagulant treatment in some form is highly desirable. Current opinion regarding the effective and safe way of anticoagulation is outlined in the section on thromboembolic disease. Measures aiming at the prevention of infective endocarditis should be instituted in appropriate situations, including the period of childbirth. The advantages of biologic valves in relation to pregnancy are clearly shown in the comprehensive survey undertaken by Oakley and Doherty,5‘j although their long-term durability may not be as good as that of artificial valves. EFFECTS OF PREGNANCY ON THE LONG-TERM COURSE OF RHEUMATIC HEART DISEASE

Although several patients with rheumatic heart disease date retrospectively the deterioration of their condition to a period which closely follows a pregnancy (and in rare occasions there may indeed exist objective evidence of such a sequence of events), most workers with experience of long follow-up studies believe that the remote prognosis is not influenced by one or more pregnancies. Any attempt to determine the long-term effects of pregnancy on rheumatic heart disease has always been difficult, mainly because of the variable natural history of the disease, depending largely on the nature of the dominant valve defect, and the intrinsic difficulty of finding a clinical control series of statistical validity. The reliable solution of this problem has been made even more difficult, perhaps impossible, by the introduction of cardiac surgery and the benefits derived from it. Nevertheless, the numerous studies dealing with this problem have provided important data on many aspects of the natural history of rheumatic heart disease. One group of workers took death as an endpoint and they found that in 3 groups of patients with rheumatic heart disease who survived at least to 40 years of age, namely parous women, nulliparous women and men, the average age at death was identical.57 Haig and Gilchrist studied a large group of patients over a period of up to 10 years after pregnancy and they expressed the opinion that pregnancy could be responsible for causing heart failure a few years earlier than would be the case 34

in the “usual” course of events. Wilson and Greenwood5g followed up women with rheumatic heart disease who developed heart failure during pregnancy and found that they did not die at an earlier age than a comparable group of nulliparous women. Miller and MetcalfeGo concluded after reevaluating the cardiac status in more than 100 patients with rheumatic heart disease 4 years after pregnancy that there was no evidence that a permanent deterioration in the cardiac condition could be directly attributed to pregnancy. In a series of comprehensive studies, Gorenberg and ChesleyGl calculated the annual death rate up to 14 years after pregnancy and concluded that longevity, even in patients with severe rheumatic heart disease, was not adversely affected by childbearing. In the study of Maynard and Grover,62 the most favorable survival rate was achieved by women who had 2 or more pregnancies, which obviously reflects a selective factor. In his latest analysis of data relating to more than 300 patients followed up for more than 30 years after the first observed pregnancy, Chesleyfi3 stated that there was no indication that repeated pregnancies may have had an adverse effect on the survival of women. We have attempted to study the long-term effects of pregnancy on the course of rheumatic heart disease in a personal series of 749 women who have been closely followed up for 8,050 patient-years after pregnancy. About 16.5% of the patients developed heart failure during the follow-up period at the average age of 37.4 years. The average time that elapsed between the first observed pregnancy and the onset of heart failure was 10 years (l-20 years). When the patients were divided into groups according to parity, the incidence of heart failure and the average age at which it developed were virtually identical in lowparity groups (1 or 2 pregnancies) and high-parity groups (3 or more pregnancies). Of all patients in sinus rhythm, 21% developed atria1 fibrillation between 1 and 26 years after pregnancy (average 10 years) at the average age of 39 years. Systemic embolism occurred in 10% of the patients during the follow-up period. In a subgroup of 400 unselected patients with dominant mitral stenosis we analyzed the data in respect to severity of the disease, onset of heart failure, atria1 fibrillation, systemic embolism and death rate up to the time of cardiac surgery, if this was performed. We compared these findings with the course of the disease in 180 patients (152 nulliparous women and 28 men) with dominant mitral stenosis of a comparable severity and age at the start of the study. This analysis showed that the incidence of the above complications, including mortality, and the age of the patients at the time of the development of these complications was virtually the same in the “pregnancy” and in the “control” series. In fact, the “pregnancy” series showed a marginally more favorable course, which may be due partly to, perhaps, closer supervision and partly to an inherent selective factor. 35

The difficulties and pitfalls of clinical comparisons are fully appreciated. There is a possibility, indeed, that the early deterioration of the cardiac condition after delivery in isolated cases cannot be diverted from the effects of pregnancy. Nevertheless, we concur with the opinion of a number of previously mentioned workers that there is no statistically valid evidence that pregnancy, if survived, accelerates the long-term progression of rheumatic heart disease. THROMBOEMBOLIC

DISEASE

There is a physiologic rise in several blood coagulation factors in pregnancy, especially in the fibrinogen levels and in factors VII, VIII, and X. Furthermore, there is a significant depression of fibrinolytic activity. These changes result in a hypercoagulable state which is likely to be aggravated by the presence of cardiocirculatory disorders. VENOUS

THROMBOSIS

It is rather difficult to establish reliably the incidence of venous thrombosis in normal pregnancy since it is probable that more than a few cases remain clinically silent. In a large series of more than 25,000 deliveries, superficial thrombophlebitis was reported in 1.3% and deep vein thrombosis in 0.19% of the cases.64 Venography can be safely used in pregnancy and is considered to be the method best adapted to the requirements of pregnancy. The use of ultrasound examination as a noninvasive method should be ideal in pregnancy, but it is less reliable than venography. Deep venous thrombosis is a dangerous condition because of the risk of pulmonary embolism; therefore, it is essential to pay close attention to factors favoring its development. Obesity, varicose veins and anemia are important predisposing factors. Also, physiotherapy with planned leg exercises should be encouraged in patients who are confined to bed for longer periods. If manifest signs of thrombophlebitis appear, anticoagulant therapy should be instituted at once and maintained for several months, possibly also for a period after delivery, in an attempt to prevent multiple small pulmonary emboli and the development of postpartum pulmonary hypertension. If the inflammation is severe, antibiotic therapy may be advisable. Rest in bed is necessary with gentle movements of the toes and of the ankle until signs of regression of the thrombotic process appear. PULMONARY

EMBOLISM

In many instances of pulmonary embolism the classical clinical signs are not present and a high index of suspicion is neces36

sary to recognize early and not-too-severe cases. Early diagnosis is essential as a severe episode of embolization is often preceded by one or more minor attacks .65.66 On the whole, the presenting clinical signs depend largely on the size of the embolus and on the presence or absence of pulmonary infarction. In mild cases the patient may show only slight transient dyspnea with a cyanotic tinge, and tachycardia. Pulmonary angiography and/or radioactive isotope lung scan can be helpful in establishing a firm diagnosis. Appropriate precautions should be taken to reduce the radiation risks to a minimum. Pulmonary embolism can occur at any stage of pregnancy. In the past it had been regarded mainly as a puerperal complication, and its occurrence in the antepartum period has been less well appreciated. The frequency and high risk of pulmonary embolism in the antepartum period has become evident in more recent reports. Ullery6’ analyzed 135 cases of antepartum phlebothrombosis giving rise to 25 episodes of pulmonary embolism with a 60% mortality rate. Sibthorpe6* reported 3 cases of pulmonary embolism that occurred before delivery, with 1 maternal death. In a series of 72 cases of deep vein thrombosis and/or pulmonary embolism studied by Henderson et al.‘jg there was an almost equal distribution of both conditions in the antepartum and postpartum periods. Of the 20 cases of antepartum pulmonary embolism, 10 occurred in the 1st trimester, 1 in the second, and 9 in the 3d trimester. In this series, there were 2 maternal deaths in the antepartum group, 1 death among the 16 cases of postpartum pulmonary embolism and 1 death in the small group of 4 patients who developed pulmonary embolism following abortion. The authors concluded that thromboembolic disease has been decreasing in the puerperium but is on the increase in the antepartum period, In our own study, 16 episodes of pulmonary embolism (1.5% of all pregnancies complicated by rheumatic heart disease) occurred in the antepartum period (6 in the 2d and 10 in the 3d trimester) and 4 cases (0.4%) were observed early after delivery.lg This distribution shows again the tendency for this complication to occur more frequently before than after delivery. In our series, one episode of pulmonary embolism was fatal, on the 23d postpartum day, 13 days after the onset of atria1 fibrillation. This death occurred in 1942, before current prophylactic and therapeutic measures were available. In the group of 19 nonfatal cases, 1 episode of pulmonary embolism followed termination of pregnancy and 2 episodes were observed after delivery by cesarean section. Massive pulmonary embolism has been reported in pregnancy on several occasions. Evans et a1.66 described 2 patients who developed massive pulmonary embolism during the 1st trimester. The diagnosis was confirmed by pulmonary angiography. Both patients survived, but the pregnancy was terminated in 1 because of a recurrence 7 days after emergency clipping of the 37

inferior vena cava. -Several other cases of massive pulmonary embolism have been reported in pregnancy.70-73 It is important to realize that massive pulmonary embolism, which is a me& serious emergency situation, can occur in the absence of overt venous thrombosis. Because of this, some centers have advocated prophylactic anticoagulants in patients with a combination of risk factors, mainly a history of thrombophlebitis in a previous pregnancy, the use of oral contraceptives with only a short time interval between their discontinuation and conception, or advanced age and high parity. However, the use of anticoagulants in such a situation in the absence of a direct therapeutic indication must be a matter of clinical judgement in the individual case. The potential risk of pulmonary embolism must be balanced against the risk of anticoagulants. After pulmonary embolism has been firmly diagnosed, or even highly suspected, the immediate institution of anticoagulant therapy, or its continuation, as the case may be, is mandatory and should be maintained in one form or another during the remainder of pregnancy and for a few weeks after delivery in order to protect the patient against reembolization. In patients who do not appear to be very ill, intravenous heparin for a few days to a week, followed by oral anticoagulants, is the preferred treatment. In more severe cases, a thrombolytic agent such as streptokinase should be considered. Comparative studies in larger series of the value of heparin and streptokinase showed that resolution of the thromboembolic process as judged by hemodynamic and arteriographic findings was significantly more favorable in the streptokinase-treated patients.72 Hall et al.73 observed rapid clinical improvement in a 29-year-old woman in the 32d week of gestation following the administration of streptokinase, which was continued for nearly 2 days, including labor and a few hours post partum. The patient received 600,000 units of streptokinase over half an hour and then 100,000 units hourly. She had a spontaneous vaginal delivery 38 hours after commencement of streptokinase therapy. A tendency to bleeding can be readily controlled and fibrinolysis can be reversed, should this become necessary, by aprotinin (Trasylol). In patients who are critically ill due to life-threatening massive pulmonary embolism, pulmonary embolectomy may have to be considered. McGuire and Smith’O reported a successful outcome of pulmonary embolectomy in a 22-year-old woman in the 3d month of gestation and suggested that pulmonary embolectomy was indicated in the presence of circulatory failure, cyanosis and right ventricular strain. Multiple pulmonary emboli can give rise to a similar clinical picture. Such a situation was observed by Cachera et a1.71 in a 25year-old woman in the 7th month of her pregnancy, in whom several blood clots were surgically removed from the distal vessels of both lungs. Subsequent38

ly, the inferior vena cava was ligated. The patient had a normal delivery 4 weeks after operative treatment. In recurrent pulmonary embolism, surgical interruption of the vena cava may prove often, but not invariably, an adequate therapy to prevent further embolization.66 A special form of pulmonary embolism is amniotic fluid embolism, which occurs during labor or shortly afterwards. It is a comparatively rare condition, but it carries a high maternal mortality. There are a good number of documented cases in the world literature confirming the presence of amniotic fluid squames in the lungs and/or right-sided heart blood.74 The clinical picture is similar to that of thrombotic pulmonary embolism in many respects. The main features are acute respiratory distress, cyanosis and arterial hypotension with circulatory failure. Defibrination due to intravascular clotting in the lungs occurs in a large proportion of cases. Therapy consists of administration of oxygen by intermittent positive pressure, sedation and measures to combat metabolic acidosis and the hypotensive state. Hydrocortisone may be helpful. SYSTEMIC EMBOLISM

In the childbearing age, systemic embolism occurs in the great majority of cases in association with rheumatic heart disease, mainly as a complication of mitral stenosis. The overall risk of systemic embolism is about 1.5 per 100 patient-years in chronic rheumatic heart disease, 0.8 in sinus rhythm and 4.6 in atria1 fibrillation. In our experience, systemic embolization in sinus rhythm occurred at the same rate in pregnancy as in the nonpregnant state, but in atria1 fibrillation the risk was more than twice as great during pregnancy. Seventy-five per cent of the embolic episodes occurred in pregnancy and 25% in the puerperium. USE OF ANTICOAGULANTS IN PREGNANCY

The indications for continuing therapy with anticoagulants during pregnancy as a long-term project or for instituting such therapy for a short period are governed by the same principles as in the nonpregnant state. However, the use of anticoagulants during pregnancy requires definite modifications and it has, indeed, certain limitations. Oral anticoagulants cross the placental circulation and may cause hemorrhage and tissue damage in the fetus. Furthermore, there is now sufficient evidence that they may have a teratogenic effect if given to the mother in early pregnancy, during the period of organogenesis.75, 76 The usual abnormalities found in the infants were hypoplasia of the nasal bones, chondrodysplasia 39

punctata and mental retardation. On the other hand, heparin, with its much higher molecular weight, does not reach the fetus through the placental circulation, but its long-term use by the intravenous reute may not be always practicable. Obviously, anticoagulant therapy in some form is essential in patients with deep vein thrombosis, pulmonary embolism or artificial heart valves. A strong case for anticoagulant treatment during pregnancy can also be made in patients with mitral valve disease and atria1 fibrillation who have a history of previous systemic embolism. In the light of present knowledge, the combination of heparin and oral anticoagulants is the best available method.77 An acceptable procedure is to give heparin during the 1st trimester, then oral anticoagulants until about the 37th or 38th week, and heparin again during the last 2 or 3 weeks instead of oral anticoagulants, in order to minimize the risk of bleeding complications in the neonate. It should be safe to resume oral anticoagulants 24 hours after delivery. It is a reasonable practice to give vitamin K to the newborn31 Recent observations suggest that oral anticoagulants are not contraindicated in breast-feeding women.78 Metcalfe and UelandG stated recently that subcutaneous heparin therapy throughout pregnancy is practicable and indeed preferable to other methods. Spearing et a1.7s have suggested self-administered subcutaneous heparin of the order of 10,000 units twice daily, which they regarded as safe and effective. Further studies should clarify whether heparin given in comparatively low doses and subcutaneously over a longer period can prevent thromboembolic complications in patients at high risk. During oral anticoagulant therapy, it is important to be aware of the potential hazards of drug interactions. There are numerous drugs that may increase or decrease the sensitivity to oral anticoagulants. In practice, such drugs may be prescribed inadvertently or taken by the patient through self-medication. Drug interaction is a complex process; some are well documented, others only suspected. The commonly used drugs that increase sensitivity to oral anticoagulants are salicylates, phenylbutazone and related drugs, and anabolic steroids. Clofibrate has possibly a similar effect. Barbiturates are an important group of drugs that decrease sensitivity to oral anticoagulants. In addition to drugs, there are intrinsic disorders that influence sensitivity to oral anticoagulants in one way or the other, such as hepatic dysfunction, malabsorption with vitamin K deficiency and, possibly, genetic factors. CONGENITAL

HEART

DISEASE

Congenital heart disease has been reported to occur in slightly less than 1% of all live births.80 Until about 2 decades ago, it 40

had been generally reported that in adults, congenital heart disease formed about 2% of all types of heart disease. In pregnancy, about 10% of the patients found to have heart disease were classified as suffering from congenital heart disease.g, 31 During the past 2 decades, an important change has been taking place in Western countries in the proportional distribution of some types of heart disease encountered in pregnant women. The most striking features are the absolute decrease in the incidence of rheumatic heart disease and the increase in the number of women with congenital heart disease seen in antenatal clinics, due undoubtedly to palliative or corrective cardiac surgery carried out before the childbearing age. Although patients with already surgically treated congenital heart disease are now seen in antenatal clinics on an increasing scale, there is still a large proportion of patients who have not undergone cardiac surgery. Most patients with acyanotic congenital heart disease in the latter group tolerate pregnancy well and there is no increase in fetal loss. Admittedly, certain conditions, like aortic stenosis and coarctation of the aorta, require special consideration. On the other hand, malformations associated with pulmonary hypertension, just as cases of surgically uncorrected cyanotic congenital heart disease, constitute a highrisk group. In general, the main risks are myocardial failure, acute cardiocirculatory collapse in certain types of congenital cardiac malformation and bacterial infection at the site of the defect. In practice, cardiac surgery is rarely required in congenital heart disease during pregnancy. On the rare occasions when surgical intervention is advisable, the principles are the same as in rheumatic heart disease, namely, closed cardiac surgery can be performed at any stage of gestation, but open heart surgery with cardiopulmonary-bypass should be avoided, if possible, in early pregnancy during the period of organogenesis. ARTERIOVENOUS

SHUNTS

Although the 3 conditions discussed here, i.e., persistent ductus arteriosus and atria1 and ventricular septal defect, have some common basic hemodynamic features, the mechanisms of shunting and the clinical aspects are quite different and require separate consideration. PERSISTENT DUCTUS ARTERIOSUS. -Persistent ductus arteriosus as a dominant defect has been observed in about 15% of all cases of congenital heart disease and it occurs more frequently in women than in men.8o It forms about 10% of all cases of congenital heart disease encountered in pregnancy, obviously with a wide range of variation in different hospital series. Furthermore, owing to prevailing opinion for some time now, virtually 41

all known cases of persistent ductus, including those entirely free of symptoms, have been surgically treated in early childhood, so that more and more patients are now seen in antenatal clinics after operative closure of the duct. A pregnant woman with an unoperated duct is now a rarity. In the presence of a not-too-large and uncomplicated ductus, a condition characterized clinically by a continuous systolic-diastolic murmur, there is an uninterrupted left-to-right shunting caused by the great difference in pressure between the aorta and pulmonary artery during both systole and diastole. These patients are symptom-free and this is the clinical pattern seen in most patients of childbearing age among those who have not yet undergone surgical closure of the duct. These patients usually tolerate the hemodynamic burden of pregnancy as a rule satisfactorily. Nevertheless, heart failure may occasionally develop and, in fact, in 1960 Mendelson31 reviewed 204 pregnant patients not operated on and found a maternal mortality of 5.5% heart failure being the main cause of death. The other potential complication in pregnancy is bacterial infection of the duct. With increase in pulmonary vascular resistance and in pulmonary artery pressure, the volume and direction of the shunting depend on the relative resistance and pressures in the systemic and pulmonary vascular systems. Pregnancy at this stage of the disease carries an increased risk, not only because of the existence of a combined left ventricular volume and right ventricular pressure load, but also on account of the specific hazards of pulmonary hypertension. In the presence of severe pulmonary hypertension, the pregnant patient is at risk from circulatory collapse rather than from progressive heart failure. Even in the absence of pulmonary hypertension, a transient reversal of the shunt can occur immediately after delivery, if there is a significant blood loss resulting in a sudden fall in systemic blood pressure. This is a readily controllable situation. Should heart failure develop during pregnancy, closure of the duct can be undertaken without increased risk to the mother or fetus. Infection of the duct is also a complication that may require cardiac surgery without delay. Mendelson31 reviewed the case histories of 24 patients in whom operative closure of the duct was performed during pregnancy. In this series, there was no maternal death and only 1 fetal loss, which was due to spontaneous abortion. ATRIAL SEPTAL DEFECT. - Atria1 septal defect forms about 17% of all types of congenital heart disease in adults and is about twice as common in women as in men.80 In uncomplicated atria1 septal defect, the arteriovenous shunt puts a direct load on the right ventricle and increases the pulmonary blood flow according to the magnitude of the shunt. The pulmonary vascular system with its low resistance readily ac42

commodates the increased blood volume and the pulmonary artery pressure remains within normal limits. Thus, patients with uncorrected atria1 septal defect of the secundum type may have no symptoms and no evidence of impaired cardiac function until after the childbearing age. Congestive heart failure is not uncommon in the 5th decade or later, when it is often associated with atria1 arrhythmias. Infective endocarditis is hardly ever observed. In accordance with the natural history of the defect, pregnancy and also multiple pregnancies are usually well tolerated, without any increased risk to mother or fetus. Nevertheless, there have been in the past well-documented cases of heart failure and maternal deaths.31 Another rare but well-documented complication is transient reversal of the shunt with cyanosis due either to a sudden fall in arterial blood pressure or to acute pulmonary hypertension secondary to pulmonary embolism.s* ls Although pregnancy carries an increased risk in the presence of persistent pulmonary hypertension associated with a secundum atria1 septal defect, or in a primum defect, the literature contains several reports of a successful outcome. Three of our 36 patients studied in 65 pregnancies had severe pulmonary hypertension and had uneventful pregnancies. Atria1 septal defect is occasionally associated with mitral stenosis, the so-called Lutembacher’s disease. In this situation, the left atria pressure is not usually high and the clinical picture is dominated by the atria1 septal defect. Patients with Lutembacher’s disease have usually uncomplicated pregnancies, as did 2 of our own patients. Operative closure of the defect has to be considered during pregnancy if heart failure develops and medical treatment fails to bring about prompt improvement. Episodes of atria1 tachycardia, persisting atria1 flutter or fibrillation are not uncommonly associated with atria1 septal defect, and they do not necessarily cease after successful closure of the defect. In fact, there have been cases in which such atria1 tachyarrhythmias first appeared after operative treatment. Admittedly, these arrhythmias develop usually after the childbearing age. Should they appear during pregnancy, antiarrhythmic management is governed by the same principles as outlined in the section on cardiac arrhythmias. VENTRICULAR SEPTALDEFECT.-Ventricular septal defect as an isolated lesion in children and adults is probably more common than persistent ductus arteriosus, but somewhat less common than atria1 septal defect.80 The clinical course of ventricular septal defect depends mainly on the size of the defect and on the pulmonary vascular resistance. In the presence of a small defect, the hemodynamic effects are negligible and may remain so for life. The patients are en43

tirely symptom-free and tolerate the hemodynamic burden of pregnancy without difficulty. However, the potential risk of infective endocarditis is just the same as in large defects, if not greater. When.the defect is large but the pulmonary vascular resistance is still normal, the pulmonary blood flow can exceed significantly the systemic blood flow. With these changes, the heart size can get progressively larger and heart failure may develop in the 3d or 4th decade. Accordingly, pregnancy in the presence of a large defect may not run an uncomplicated course. If ventricular septal defect is associated with increased pulmonary vascular resistance and right ventricular hypertension, the shunt may become bidirectional, with transient or permanent cyanosis. Pregnancy at this stage carries an increased risk, whose gravity depends on the degree of the hemodynamic changes. A review of 110 cases of patients with ventricular septal defect complicating pregnancy who were not operated on showed a heart failure rate of 8% and a mortality of 5.5%.31 Three of the 6 reported deaths were caused by circulatory collapse following delivery; congestive heart failure, paradoxical embolism and infective endocarditis were each responsible for one of the 3 other deaths. Because a number of infants with ventricular septal defect are now treated surgically because of heart failure and lack of satisfactory response to medical treatment, and a larger number of those with a shunt in excess of 2:l undergo elective closure of the defect in childhood, more and more patients are reaching the childbearing age and becoming pregnant after cardiac surgery. Late results of the operation are good and these women have uncomplicated pregnancies. The outcome is less satisfactory in the occasional case with a residual shunt, or postoperative heart block or significant pulmonary vascular disease; in these situations, pregnancy requires very close supervision. In patients not operated on, the need for cardiac surgery during pregnancy should arise only very rarely. It should only be considered in patients who develop heart failure and do not respond adequately to medical treatment or in those who have severe bacterial endocarditis. VENOARTERIAL SHUNT

Although the association of pregnancy and cyanotic congenital heart disease concerns only a small group of patients, it constitutes a most important cardiologic and obstetric problem, posing a greatly increased risk to both mother and fetus. Only 2 conditions will be discussed here, namely, Fallot’s tetralogy and Eisenmenger’s syndrome; other types of cyanotic congenital heart disease are rarely seen in association with pregnancy and experience is understandably greatly limited. 44

FALLOT’S TETRALOGY. -This condition accounts for less than 15% of all cases of congenital heart disease.80 It is found ,more often in male than in female patients. In the past, a large number of these patients died in infancy or early childhood, and only a few naturally selected patients reached the childbearing age. The causes of death were mainly heart failure, respiratory infection, infective endocarditis and cerebral complications. With the advent of antibiotic therapy and the introduction of palliative and, more recently, corrective cardiac surgery, the situation has significantly changed. In patients with Fallot’s tetralogy untreated surgically, pregnancy carries a maternal mortality of more than 4%81 and a fetal loss of more than 30%.31 The combination of a low peripheral vascular resistance peculiar to the pregnant state and the fixed obstruction created by the pulmonary stenosis and potentiated by right ventricular outflow tract obstruction tends to increase the right-to-left shunt and the degree of cyanosis. From the prognostic point of view, recurrent syncope, a hematocrit reading in excess of 60%, oxygen saturation of less than 80% and a right ventricular pressure exceeding 120 mm Hg are considered unfavorable signs.** Labor and the immediate postdelivery period are the most critical times. Most deaths have been caused at this stage by hypotension with circulatory failure. Progressive heart failure as a cause of death is less common. More recently, Batson summarized the findings in 8 patients with Fallot’s tetralogy who had a total of 27 pregnancies. There was no maternal death, but fetal loss still amounted to more than 50%, due mainly to abortions, but also to stillbirths and neonatal deaths. Dubourg et a1.84 reported the case of a 38year-old woman with Fallot’s trilogy (pulmonary stenosis, atria1 septal defect and right ventricular hypertrophy) who underwent pulmonary valvotomy and closure of the atria1 septal defect in the 3d month of her pregnancy. Her condition had greatly improved, but she aborted 3 months later. In another patient with Fallot’s tetralogy reported on by Baker et a1.,85 pulmonary valvotomy was carried out at 24 weeks’ gestation with a satisfactory outcome. Palliative cardiac surgery of the anastomotic type and mainly total correction of the defect, which is now being carried out electively in early childhood on an ever increasing scale, can greatly improve the prospects of successful childbearing (Fig 5). EISENMENGER’S SYNDROME. -The characteristic features of Eisenmenger’s syndrome are pulmonary hypertension with high pulmonary vascular resistance and right-to-left shunt with central cyanosis. The site of the shunt may be at the aortopulmonary, atria1 or ventricular level. It has been observed in about 3% of all cases of congenital heart disease in children and adults.so 45

Fig 5.-Tetralogy of Fallot. A, chest x-ray film taken when the patient was 2 years of age. She underwent pulmonary valvotomy at the age of 4 and Potts anastomotic operation at 7. Total correction of the defect was carried out when she was 27. Two virtually uneventful pregnancies occurred 1 and 2 years, respectively, after total correction. 6, chest x-ray film taken after second pregnancy.

The disease shows a progressive course, with important complications, such as heart failure, pulmonary infarction, various forms of arrhythmias and syncopal episodes. Death often occurs before the age of 40 years. This condition is not amenable to cardiac surgery and pregnancy carries a considerable risk. Jones and Howittsl reported a maternal mortality of 27%. Neilson et a1.*6 found an even higher death rate, of the order of 45%, and the highest death rate, namely, 70%, was recorded by Pitts et al .87 This is in sharp contrast to the series of 11 patients reported on by Batson: who survived 23 pregnancies, although the fetal loss was as high as 26%. However, this was a retrospective study and details of the number of cases completing pregnancy with the features of Eisenmenger syndrome were not given. Most deaths occur in the very early puerperium and often suddenly or after a short period of significant increase in cyanosis. Cutforth et al.88 monitored closely several episodes of syncope. They found that all were related to the assumption of the erect posture or to physical effort. The mean pulmonary artery pressure rose at this time. They postulated that an increase in right-to-left shunt had occurred, which may have resulted in sufficient anoxia to lead to syncope and death. They have also shown that straining during or after delivery can cause very high right ventricular pressures that could initiate fatal arrhythmias. Midwall et al.89 studied the pulmonary hemodynamits during labor in patients with the Eisenmenger syndrome. 46

They found that uterine contractions resulted in a decrease in the ratio of pulmonary-to-systemic blood flow. In their experience, high concentrations of oxygen produced a fall in pulmonary arterial pressure, with an increase in the ratio of pulmonary-to-systemic blood flow. They have also observed that oxytocic drugs, positional changes and epidural anesthesia for delivery did not affect adversely the pulmonary hemodynamics. Eisenmenger’s disease is not currently amenable to palliative or corrective cardiac surgery, and the clinical implications are that women suffering from this disease should be advised against undertaking pregnancy. In pregnant patients, therapeutic termination of pregnancy must always remain an individual approach and decision, but on general grounds it should be seriously considered. At the same time, it is important to take into account that the use of oral contraceptive agents is highly dangerous in this situation. DOMINANT VALVE AND/OR VASCULAR DISEASES

Primary valvar and vascular disorders occur either in isolation or in association with other congenital defects. We shall only discuss disorders that are not uncommonly seen in adults and in pregnant women. PULMONARY STENOSIS.-Isolated pulmonary stenosis forms about 13% of all cases of congenital heart disease in children and adults.*O It occurs with equal frequency in both sexes. The natural course of the disease depends largely on the height of the right ventricular pressure. It is not possible to draw a sharp dividing line, but some patients can remain symptom-free for a considerable time, including the whole period of childbearing age, despite a right ventricular pressure in excess of 80 mm Hg. A number of patients with pulmonary stenosis with intact septum are treated surgically in infancy or in very early childhood as a matter of urgency, if they develop severe hypoxemia. Elective operation later in childhood is broadly considered to be indicated if there is a gradient across the valve stenosis in excess of 50 mm Hg. The raised blood volume in pregnancy is likely to put a further load on the right ventricle. However, this additional load is usually well‘ tolerated, as judged by the fact that heart failure only rarely occurs during pregnancy. A review of .59 cases of unoperated pulmonary stenosis complicating pregnancy revealed 5 instances of heart failure, but no maternal death.31 In this series, there was only one fetal loss due to therapeutic abortion. In our personal series of 12 pregnancies complicated by isolated pulmonary stenosis, 10 pregnancies were uncomplicated, 1 ended in miscarriage and a 21-year-old patient developed right47

sided ment nated sider

heart failure in- her second pregnancy. After medical treatand control of the heart failure, the pregnancy was termiby hysterotomy. This was in 1952. Today we would conpulmonary valvotomy in a similar type of case.

AORTIC STENOSIS.-Congenital obstruction to left ventricular outflow, which constitutes about 5% of all cases of congenital heart disease, can be valvar, subvalvar or supravalvar. Valvar stenosis forms about 70-80% of the cases. The aortic valve is often bicuspid. The condition has a male predominance. Bicuspid valves show a greatly increased tendency to early calcification, resulting in significant aggravation of the stenosis. The natural course of congenital aortic stenosis is variable and documentation has become even more difficult since the introduction of cardiac surgery. A number of cases are complicated by cardiac failure in early life, but many of these have associated endomyocardial disease. In the symptom-free group, occasional sudden death is known to occur in childhood. Many patients maintain their clinical fitness well into adult life, but the prognosis is always guarded. Once one or more of the main symptoms, namely, breathlessness, angina or syncope, have developed, the outlook is grave unless the aortic obstruction is surgically relieved. Sudden death, presumably due to ventricular arrhythmias, is not uncommon. The risk of pregnancy in patients with surgically untreated aortic stenosis has to be evaluated in the light of the natural history of the disease. Many patients with even severe aortic stenosis with a gradient of 100 mm Hg or so across the aortic valve can have uneventful pregnancies. At the same time, the absence of symptoms in perhaps less severe aortic stenosis does not guarantee an uncomplicated pregnancy. Left ventricular failure or sudden death are the main potential hazards. Infective endocarditis is also a recognized complication, especially in the presence of a bicuspid valve. Pregnant patients with moderateto-severe aortic stenosis should be firmly advised to avoid undue physical exertion. An integral part of the management is to ensure that facilities for prompt cardiopulmonary resuscitation are available, should the need arise. The onset of left ventricular failure in pregnancy or repeated syncopal episodes may constitute an indication for aortic valvotomy without delay. Admittedly, aortic valvotomy is not a perfect operation and these patients frequently require subsequent replacement of the aortic valve, but it is decidedly less traumatic in the pregnant state and it reduces the risk of sudden death. In reviewing the subject of congenital aortic stenosis in relation to pregnancy, Robinson et a1.s0 warned against the use of oxytocic drugs in this condition. In their experience, the intravenous administration of 1 cc of synthetic oxytocin resulted in ventricular fibrillation and death in a 29-year-old pregnant woman. They postulated that the oxytocin-induced increase in 48

cardiac output was brought about by an increase in both stroke volume and heart rate. In patients with aortic stenosis, these factors would increase the pressure gradient across the aortic valve and the velocity of ventricular ejection, leading to increased myocardial oxygen consumption and diminished coronary blood flow. The final effects would be myocardial hypoxia and enhanced ventricular irritability. The above-mentioned patient was found to have an unsuspected myocardial infarction, in addition to aortic stenosis; the question remains open whether a similar sequence of events would develop in patients without acute myocardial injury. COARCTATION OF THE AORTA.-Coarctation of the aorta is responsible for about 7% of all cases of congenital heart disease in children and adults.60 It is more common in male than in female patients. Coarctation of the aorta is not uncommonly associated with a bicuspid aortic valve and occasionally with a cerebral aneurysm. A large number of patients remain free from symptoms for a considerable time and the condition may be first diagnosed on routine examination in late childhood or early adult life. The main hazards of the disease are complications derived from the hypertensive state, the pathologic processes of the aorta itself and infection of the aortic defect or of the associated bicuspid aortic valve. In uncomplicated coarctation, pregnancy does not necessarily constitute an added risk, but this can be only retrospectively established; collective experience with large numbers of cases has revealed a maternal morality far in excess of the average maternal mortality in patients with cardiac disease, namely, about 3.5% in respect of pregnancies and about 9% in respect of patients. In a comprehensive review of a series of 147 patients who had 380 pregnancies, there were 13 maternal deaths: 6 patients died from rupture of the aorta, 2 from cerebrovascular accidents, 3 from heart failure, 1 from bacterial endocarditis of the aortic valve and 1 from undetermined causes.s1 The association of coarctation and aortic dissection is well known and may be more common in pregnancy than in the nonpregnant state. It represents a greatly increased risk to the pregnant woman. There is an increased fetal loss in pregnant patients with unoperated on coarctation, possibly due to impaired blood supply to the uterus and placenta in the presence of inadequate collateral circulation. Burwell and Metcalfe’J reported a fetal mortality of 13%. In contrast to essential hypertension, the hypertensive state in coarctation is rarely potentiated by pregnancy-induced hypertension (toxemia of pregnancy) and, therefore, this latter condition cannot be considered a contributory factor to the increased fetal loss. The question of the best method of delivery of patients with 49

coarctation has always been a matter of discussion. In the past, several workers have favored delivery by elective cesarean section. However, most centers are now of the opinion that in uncomplicated cases and without obstetric reasons there is no clear indication fo?%esarean section and normal vaginal delivery at term should be the preferred method. In this context it is noteworthy that the strain of labor does not appear to be an important factor in the process of aortic rupture, as proved in a collected series of cases in which more than 80% of the aortic ruptures occurred before the onset of labor.s2 Furthermore, aortic rupture appears to be unrelated to the height of the arterial blood pressure, which, in any case, tends to fall in the 2d trimester, similar to the behavior of the blood pressure in normal pregnancy, and may not rise again to its original level in late pregnancy. Surgery has an important part to play in the management of coarctation of the aorta. Some infants develop severe heart failure and are treated surgically as an emergency measure. Elective resection of coarctation is carried out in a large number of patients later in childhood. Thus, more and more women are reaching the childbearing age after surgical resection of the coarctation and as shown by experience, usually have uneventful pregnancies. Among the patients with surgically uncorrected cases of coarctation in adult life, a number have received surgical treatment during pregnancy.g, lg, 31 Mendelson31 summarized reported experience regarding operative treatment of coarctation in relation to pregnancy. In a group of 51 patients operated on before pregnancy there was no maternal death and the fetal loss was 20%. In a small group of 8 patients who underwent resection of the coarctation during pregnancy there was 1 maternal death and 1 fetal loss. The patient who died was operated on in the first month of gestation; she developed an aneurysm at the site of the anastomosis, which ruptured in the 7th month of pregnancy. Pregnancy is obviously not an ideal time to advise elective resection of the coarctation. In fact, Burwell and Metcalfes pointed out some time ago that operative treatment of coarctation should be avoided during pregnancy, if possible, because of the risk arising from the frequently encountered pathologic changes in the aortic wall. We concur with the opinion of many workers that in uncomplicated cases, medical management during pregnancy is preferable to surgical treatment, except perhaps in the very occasional patient with a systolic blood pressure well in excess of 200 mm Hg, which was the case in one of our patients who underwent a successful resection of her coarctation at 20 weeks’ gestation. However, if complications develop, especially signs of aortic dissection or aneurysm, operative intervention should be considered without delay.s1 EBSTEIN’S DISEASE. - Ebstein’s abnormality is a comparatively uncommon disease. The main features of the lesion are an abnormal tricuspid valve, which is displaced into the right ventri-

50

cle, resulting morphologically in a large right atrium and a small right ventricle with impaired function. It is often associated with an atria1 septal defect and the inevitable tricuspid regurgitation can thus lead to a right to left shunt, with cyanosis and clubbing of the fingers. Although the course of the disease and the clinical manifestations are variable with the possibility of survival to an old age, the prognosis is on the whole poor. Many patients die in early adult life. The main causes of death are cardiac failure and/or serious rhythm disturbances. The patient’s condition can be remarkably improved and activity is virtually restored to normal by tricuspid valve replacement and closure of the atria1 septal defect if the latter is present. However, the risk from serious arrhythmias persists. Although a number of uneventful pregnancies have been reported in patients suffering from Ebstein’s disease, serious complications are known to occur.g3, g4 There is an increased danger of right ventricular failure precipitated by the hemodynamics of pregnancy, owing to the inability of the malfunctioning right ventricle to accommodate effectively the increased blood volume. In this way the tricuspid regurgitation and the right-to-left shunt can also become exaggerated. Further risks are bacterial endocarditis and paradoxical embolization through the atria1 septal defect.g4 The spontaneous abortion rate is high in the presence of persisting cyanosis.g3 Patients who have undergone tricuspid valve replacement have a good chance of negotiating subsequent pregnancies without complications.1s CONGENITAL HEART BLOCK

Congenital complete heart block appears to be more common in male than in female patients and is uncommonly observed in pregnant women. It can occur as an isolated lesion or in association with a congenital heart defect, mainly ventricular septal defect. The etiology is uncertain, just as in many types of congenital cardiac defect, but it is noteworthy that there is now suggestive evidence of a close relationship between maternal systemic lupus erythematosus and congenital complete heart block.s5 However, the possibility arises that these cases of complete heart block form a special group associated with endomyocardial fibrosis. Most patients with congenital complete heart block which is not associated with significant cardiac defects have uneventful pregnancies.lg, s6 The ECG of such a patient is shown in Fig 6. However, complications such as heart failure and Stokes-Adams attacks are known to have occurred. Mendelson31 summarized collective experience in a group of 25 patients who had 39 pregnancies. Heart failure developed in 1 patient and 3 patients 51

Fig B.-Congenital No clinical evidence

complete of organic

heart block heart disease.

in a 23-year-old pregnant Uneventful pregnancy.

woman.

had syncopal episodes. There was also 1 maternal death, but this patient had preeclamptic toxemia and her death did not seem to be related to the complete heart block. Stokes-Adams attacks in midpregnancy or in labor have also been observed by other workersg7, g8 There are several reports of successful pregnancies in patients in whom a pacemaker had been implanted before the start of pregnancy.gg-lO1 Collective experience would point to the following conclusions. In pregnancies with symptom-free complete heart block, the institution of prophylactic pacing is unnecessary. Should syncopal episodes occur, cardiac pacing is currently preferred treatment. The implantation of an artificial pacemaker should also be undertaken if heart failure develops. The management of delivery should present no difficulties in patients with a pacemaker. HYPERTENSIVE

DISORDERS

In this section, we intend to discuss mainly the course of pregnancy in essential hypertension and to mention only briefly the cardiac aspects of pregnancy-induced hypertension (referred to as toxemia of pregnancy in previous writings) and of pheochromocytoma. ESSENTIAL HYPERTENSION

It is generally accepted that a raised blood pressure observed before the 20th week of gestation should be regarded as unrelated to pregnancy. In practice, in a large number of women, the diagnosis of essential hypertension has already been fully documented before the start of pregnancy and some of them may be already receiving antihypertensive drugs when first seen in pregnancy. In the absence of firm data obtained before pregnancy, simple, noninvasive laboratory tests together with the clinical findings should be sufficient to rule out an important renal lesion or pheochromocytoma as a cause of the hypertension. 52

A significant proportion of pregnant women with essential hypertension show a slight fall in both systolic and diastolic pressures in the 2d trimester. This pattern, which is similar to that observed in normotensive women, occurs even in the absence of antihypertensive drug therapy. Barnes43 found a fall of at least 22 mm Hg in systolic blood pressure in 60% and a corresponding fall in diastolic pressure in 25% of 145 patients with essential hypertension findings to which he attributed prognostic significance. In the group of patients who had such a fall in blood pressure in the 2d trimester there was a fetal loss of 4.6% as compared with 16% in those patients who had no fall in blood pressure. In a large number of pregnant patients with essential hypertension who have no significant cardiac enlargement or advanced vascular changes there are no maternal complications and the fetal loss is not greater than that found in normotensive patients. However, a proportion of these patients develop superimposed, pregnancy-related increase in blood pressure, which leads to an increase in fetal 10~s.~~~~~~ Recent studies suggest that the plasma urate level is a reliable indicator of fetal prognosis.lo3 It is now universally recognized that antihypertensive therapy of essential hypertension favorably influences both the immediate and the long-term course of the disease by reducing the risk of cardio-, cerebra- and neurovascular complications. Accordingly, the desirability, or indeed the necessity, of undertaking such treatment at an early stage has been more and more appreciated in recent years. In keeping with this approach, most workers believe that the institution of antihypertensive drug therapy, or its continuation, as the case may be, has an important part in the management of the pregnant patient with essential hypertension. The validity of this concept is underlined again by the results of-the confidential inquiries into maternal deaths, which show that the complications arising from hypertensive disease in pregnancy form a major cause of maternal death.27 Most centers accept the view that if general measures such as adequate rest (maybe some days in bed), sedation, salt restriction and diuretic therapy (in the occasional case only in the form of severe fluid retention) fail to control the blood pressure at a level consistently not exceeding X0/90, the introduction of antihypertensive drug therapy is desirable. We believe that the satisfactory control of the blood pressure during pregnancy improves both maternal and fetal prognosis and is also likely to have a long-term beneficial effect. There are now several antihypertensive drugs that have proved their value. However, the most widely used antihypertensive agent in pregnancy is methyldopa, which is administered mainly alone and occasionally in combination with another drug. Kincaid-Smith et a1.104assessed the value of methyldo53

pa in a group of 32 pregnant women with severe hypertension, 29 of whom had had documented evidence of a hypertensive state before pregnancy. The dosage was individually adjusted in an attempt kmaintain the blood pressure at a level below 140/90 mm Hg. To achieve this, the final daily dose ranged from 500 mg to 4 gm. There were 3 fetal deaths in this group; one, however, was due to premature rupture of the membranes and, therefore, the corrected perinatal mortality was 6.2%. In the experience of Leather et a1.,lo5 methyldopa in combination with bendrofluazide was effective in pregnant patients with essential hypertension, but of no benefit to patients with pregnancy-induced hypertension. Further studies confirmed the beneficial effect of methyldopa on the course of pregnancy in patients with essential hypertension.‘06, lo7 We have closely followed the course of pregnancy in 88 patients with essential hypertension, a number of whom had been known to us before pregnancy. Of these 88,34 were receiving antihypertensive medication, mainly methyldopa. Nine patients in the treated group (26%) had an initial blood pressure of at least 190/125, the highest being 240/160. A satisfactory control of the blood pressure (140/90 or less) was achieved in 28 patients (82%). Two patients (6%) developed superimposed pregnancyrelated hypertension. There was no maternal death and there was fetal loss in 3 cases (9%). In a group of 54 patients whose cardiovascular status was on the whole comparable to that of the drug-treated group, except that it included only 3 patients with an initial blood pressure of 190/125 or higher, no antihypertensive drugs were used and the management consisted of periodic bed rest, sedation and moderate salt restriction. Of 54 patients, 10 (18%) developed superimposed pregnancy-related hypertension. The fetal loss amounted to 13 (24%). Although there is general agreement that methyldopa satisfactorily lowers the blood pressure in most pregnant women with essential hypertension, Redman et a1.1°7 have suggested that it does not necessarily prevent the development of superimposed preeclampsia as judged by the rise in plasma urate. These authors also expressed the opinion that the improved fetal outcome is not a direct result of the beneficial effect of methyldopa on the maternal blood pressure and that methyldopa may have an effect on the uterine tone, prevent midpregnancy abortion and thus improve fetal survival. Should treatment with methyldopa alone prove inadequate, a satisfactory control of the blood pressure can be achieved as a rule by the addition or oral hydralazine. In any event, when a significant reduction of the blood pressure appears to be a matter of great urgency, the use of parenteral hydralazine is likely to be helpful. The side effects of methyldopa are not serious and there is 54

nothing to indicate that the drug has a teratogenic effect. A positive Coombs’ test is uncommon within less than 6 months of treatment. Hemolytic anemia is a rare complication. /3-Adrenergic blocking agents have been used on an increasing scale in recent years in the treatment of hypertension, and experience has also been gained in their use in hypertensive pregnancy. Although there is general agreement regarding their efficacy in reducing high blood pressure in pregnancy, observations vary between their complete safety and the production of undesirable side effects on the fetus, such as low birth weight possibly due to placental insufficiency, respiratory distress and hypoglycemia.‘08-110 A study comparing methyldopa and oxpreno101 for treatment of hypertension in pregnancy was conducted by Gallery et al.“’ They found oxprenolol to be safe and effective in controlling hypertension during pregnancy, and even superior to methyldopa. There were 2 neonatal deaths in the methyldopa group and none in the oxprenolol-treated group. Current opinion favors the idea that the use of diuretics in pregnancy should be discouraged except in cases with severe fluid retention. Diuretic drugs may induce relative hypovolemia, which has a bearing on the infant’s birthweight, and they may also impair placental function.lo2 As pregnancy can be successfully managed by antihypertensive drugs and periods of prolonged rest, there is no definite medical indication for therapeutic termination of pregnancy, even in patients with accelerated or malignant hypertension, if reasonable renal function has been preserved. With regard to delivery, induction of labor or elective cesarean section in wellselected cases at the stage of adequate maturity of the fetus are likely to give best results. Even with a satisfactory control of the blood pressure there is a potential risk of intrauterine death of the fetus due to placental insufficiency in the last 1 or 2 weeks before full term. PREGNANCY-RELATED HYPERTENSION PREGNANCY, PREECLAMPSIA)

(TOXEMIA

OF

The cardiac aspects of pregnancy-related hypertension are well documented. Irrespective of whether it is superimposed on essential hypertension or occurs in a previously normotensive patient, it can give rise to acute clinical and ECG changes.lg Analysis of case histories has shown that these changes are independent on the degree of hypertension and may not be even directly related to the hypertensive state as such. The main cardiac change is the development of acute pulmonary edema, which is probably brought about by fluid retention, possibly in the presence of acute damage to the pulmonary capillaries with increased capillary permeability. ECG changes chnsist mainly of 55

T-wave inversion. Q-waves are absent. The changes are likely to be caused by focal myocardial lesions. The duration of ECG changes varies considerably; they may not only persist for a while after delivery but may even become more pronounced in the puerperium. Gross cardiac enlargement is rarely found in this syndrome. The cardiac manifestations which are similar to those reported in acute glomerulonephritis regress invariably. The treatment of pregnancy-induced hypertension does not differ from that of essential hypertension discussed above, but the control of the blood pressure is more urgent. The role of bed rest and salt restriction should be emphasized. PHEOCHROMOCYTOMA

Pheochromocytoma is uncommonly encountered in pregnancy, but it is of great importance in view of its very high maternal and fetal mortality, especially if the tumor remains unrecognized. Several reviews recorded a maternal mortality of 4050% 112,113 The diagnosis can be indeed difficult because of the variable presenting clinical picture. In one of our patients the first important clinical manifestation was acute pulmonary edema near term, with a normal blood pressure throughout’pregnancy. Another patient who had a very moderate rise in blood pressure without any symptoms a few hours before the onset of labor developed acute circulatory collapse shortly after delivery. A high index of suspicion is necessary in recognizing the existence of a pheochromocytoma and when such a tumor is suspected, the levels of catecholamines and of vanillylmandelic acid in the urine can substantiate the diagnosis. The clinical picture depends to some extent on the relative amount of epinephrine or norepinephrine secretion by the tumor.l14 The hypertensive state may be sustained or paroxysmal in typical cases, and often it is absent over long periods of observation. Hypertensive attacks can be precipitated by the process of delivery. Acute pulmonary edema and paroxysmal tachyarrhythmias are the most important cardiac manifestations. The general principles concerning the management of pheochromocytoma during pregnancy have been summarized by Smith.‘15 If the diagnosis is established in early or midpregnancy, removal of the tumor is advisable. Later in pregnancy, delivery by cesarean section may have to precede abdominal exploration and removal of the pheochromocytoma. Operative intervention should be safe today with the use of (Y- and P-adrenergic blocking agents preoperatively and complete cardiocirculatory monitoring throughout operation so as to recognize and control immediately hypotension or a hypertensive crisis or cardiac arI rhythmias. 56

CARDIOMYOPATHY

AND

PREGNANCY

Cardiomyopathy is defined as a disorder of the heart muscle of unknown etiology. Several types of cardiomyopathy have been recognized, but we will discuss here 2 types that have been extensively studied in relation to pregnancy. A dilated type of cardiomyopathy occurs in late pregnancy or in the puerperium and has been considered by several workers as a specific entity directly induced by the pregnant state. The other type is hypertrophic obstructive cardiomyopathy, which is a chronic disorder whose origin is entirely unrelated to pregnancy. PERIPARTUM CARDIOMYOPATHY

Peripartum cardiomyopathy is probably the most appropriate term for this disorder because the clinical manifestations do not necessarily appear only after delivery but often in the late stages of pregnancy. Although there is no complete unanimity of opinion as to whether a specific clinicopathological entity in direct causal relationship to pregnancy is present or pregnancy acts only as a precipitating factor in the presence of a preexisting disease, most workers are now inclined to adhere to the former hypothesis. Admittedly, the clinical pattern and the course of the disease are not uniform and there are some variations from the typical cases in different parts of the world. Accordingly, Goodwin and Oakley 116have suggested that periparturn cardiomyopathy may be a multifactorial illness and pregnancy is only one of its causative factors. Hormonal changes and autoimmune mechanisms have also been considered as precipitating factors.117 Environmental, social and nutritional factors may also play a part. llE The opinion has also been expressed that drug-induced myocardial damage may be responsible for some cases classified as cardiomyopathy of pregnancy.l18 However, its frequent recurrence in subsequent pregnancies strongly favors the view that this disorder is a specific entity in close causal relationship with pregnancy. l ls, 120 ROBERT A. O'ROURKE: Experimental

studies suggest that pregnancy may predispose to viral myocarditis. When cardiomyopathic viruses are given to pregnant rodents, almost 90% develop congestive cardiomyopathy as compared to less than 10% of nonpregnant rodents.

Peripartum cardiomyopathy is a special form of cardiomyopathy, which has been frequently observed in Northern Nigeria.lzl* l22 It occurs mainly, but not invariably, in the postpartum period. It is more readily amenable to medical treatment and carries a much lower mortality rate than the rather “typical” form observed in Western countries. It is attributed to the custom of taking large amounts of dried lake salts after delivery 57

and lying on heated mud beds. The intake of large amounts of salt in the belief that it promotes lactation possibly leads to increase in extracellular fluid and in plasma volume. Both the high sodiumintake and the excessive heat load result in an increase in cardiac work. The great majority of these patients have hypertension, but both the hypertension and the cardiac failure respond most satisfactorily to digitalis and diuretic therapy. It is of interest that left ventricular function as assessed by echocardiography and measurements of systolic time intervals did not appear to be significantly impaired in these cases and the estimated cardiac output was increased.‘** These findings do not suggest severe heart muscle disorder. PATHOLOGIC CHANGES. -The pathologic changes in peripartum cardiomyopathy encountered in Western countries represent a combination of degenerative changes and cellular infiltration. The main alterations are cloudy swelling with loss of crossstriation of muscle fibers, and cellular infiltration by lymphocytes, mononuclear cells and plasma cells. Cardiomegaly is a regular feature, and mural thrombi are frequently present. Light microscopic study of endomyocardial biopsy specimens shows loss of myofibrils and increase of collagenous fibers and electron microscopy reveals peculiar fibrous structures in the sarcoplasm.123J 124 CLINICAL ECG AND HEMODYNAMIC FEATURES.-Themostimportant clinical symptoms and signs are increasing shortness of breath, chest pain that can simulate an angina1 attack, hemoptysis, disturbances of the cardiac rhythm, embolic manifestations and progressive heart failure. Thromboembolic events occur more frequently in peripartum cardiomyopathy than in any other type of cardiomyopathy, possibly because of the hypercoagulable state that exists in pregnancy.l*O However, pulmonary embolism is probably more common than systemic embolism. The main ECG changes are ST-segment depression and Twave inversion, conduction defects and disorders of the cardiac rhythm. Hemodynamic investigations showed increase in pulmonary vascular resistance with raised pulmonary artery and pulmonary “wedge” pressures and also a raised right ventricular enddiastolic pressure. 123A decrease in cardiac output and low pulmonary arterial oxygen saturation were also reported.125 Prolonged therapy is essential, especially in the presence of severe heart failure. In addition to the usual measures against heart failure, anticoagulant therapy should be considered in view of the high incidence of thromboembolic events. Prolonged, complete bed rest has also been advocated.126 In. any event, the immediate prognosis is guarded. After severe heart failure has occurred, progression of the disease can be very rapid, with an average mortality of about 30%, ranging from 15 to 60% in var58

ious reports.l23,127,12* The long-term prognosis depends mainly on the degree of recovery from the initial episode. Study of the natural course of the disease has shown that in a group of 14 patients who made a full recovery with normalization of the cardiac size, only 2 died over an observation period averaging 10 years, and both deaths were due to noncardiac causes, whereas in the group of 13 patients who showed residual cardiomegaly, 11 have died from progressive heart failure after an average survival period of 4.7 years. 12s Subsequent pregnancies were well tolerated in the former group, but not in the latter. OBSTRUCTIVE

CARDIOMYOPATHY

AND PREGNANCY

The course of pregnancy in hypertrophic obstructive cardiomyopathy was extensively studied by Oakley et al.130 From a study of 23 patients who had 54 pregnancies they concluded that pregnancy was safe in this disorder. There was no maternal death in this series. There were 10 abortions, but no infant died in the perinatal period. On the basis of their experience, they now advise a flexible approach regarding the use of /I-adrenergic blocking agents. They believe it is justifiable to administer them in the presence of angina, but with very close monitoring of fetal growth in these cases. Otherwise, they should be withheld in order to avoid potential hazards to the fetus. Normal vaginal delivery should be the preferred method. CORONARY

HEART

DISEASE

Recent observations tend to show that coronary artery disease and acute cardiac infarction are not uncommon in young women, a large proportion of whom are exposed to one or more wellrecognized coronary risk factors, including the use of oral contraceptive agents. ~~33 Although there are inherent difficulties in estimating the prevalence of ischemic heart disease in women in the reproductive years, the survey of Oliver132 strongly suggests that the incidence of the disease is on the increase. Should currently advocated preventive approaches prove inadequate, it is very likely that there will be an increase in the number of pregnant patients with symptoms and signs of ischemic heart disease in the years to come. Considering the main recognized risk factors, it has been suggested that oral contraceptive agents increase the hazards of myocardial infarction only in those women who are already exposed to one or more of the high-risk factors. 132 Patients who have angina of effort during pregnancy do not run a higher risk of developing acute cardiac infarction than they would in the nonpregnant state over a comparable period of time. The immediate prognosis is reasonably good if due attention is paid to existing risk factors, controlling them where ap59

propriate, and adequate medical management is provided, including the possible use of /3-adrenergic blocking agents. The development of acute cardiac infarction during pregnancy presents a sqious problem. A review of 29 cases reported by various centers revealed a maternal mortality of 52%.31 Fletcher et a1.134 studied personally 5 patients who sustained acute cardiac infarction while pregnant. Their ages ranged from 36 to 41 years. There was no maternal death in this group, and only one fetal death, which was possibly the result of severe preeclampsia. A comprehensive review of reported cases was presented by Ginz.13” It was estimated that the incidence of acute cardiac infarction in pregnancy was of the order of l:lO,OOO deliveries. In 7 of the 39 cases analyzed, the attack occurred in the 1st trimester, 10 in the 2d trimester and 22 in late pregnancy or in the puerperium. The overall mortality was 28%, with the highest maternal mortality rate in the puerperium. Sasse et a1.13‘j reported the case histories of 2 young women, aged 16 and 26 years, respectively, with no known coronary risk factors who developed a transmural myocardial infarction during the 3d trimester of gestation while lying in the supine position. Both made a good recovery and had an uneventful delivery. Coronary angiograms performed a few months later were normal. The authors have postulated that the cardiac infarction was caused by coronary arterial spasm due to release of renin from the transiently ischemic placenta resulting from prolonged supine recumbency. Shaver et a1.137 described a 27-year-old woman who developed an acute anterior myocardial infarction 3 weeks after delivery. Coronary angiography revealed a primary dissection of the left coronary artery. The authors reviewed 12 other patients who developed primary dissection of a coronary artery in late pregnancy (2 cases) or after delivery (10 cases). Eleven of these died and the diagnosis was documented by necropsy. One patient survived and the findings were confirmed by coronary arteriography. Thus, there were only 2 survivors in a group of 13 documented cases. Most patients were normotensive and showed no abnormal features until the acute episode. Whether straining during the various stages of labor can lead to intimal tear with hemorrhage into the media is a matter of conjecture. The authors suggest that rupture of the vasa vasorum into the media could be the usual initial event. The principles of management of acute cardiac infarction during pregnancy do not differ from those in the nonpregnant state, but the question of anticoagulant therapy and the method of delivery may require special consideration. In view of the questionable value of anticoagulants in acute cardiac infarction and of the potential hazards of oral anticoagulants to the fetus, we believe that their use should not be generally encouraged and should be reserved for selected cases with special indication for 60

such therapy. Although a number of patients with cardiac infarction have been delivered by cesarean section, we believe that normal vaginal delivery should remain the preferred method in most cases. The safety of pregnancy subsequent to acute cardiac infarction depends on several factors. A time interval of at least 1 year between the acute attack and pregnancy, a younger age in the obstetric sense, not more than slight cardiac enlargement, the absence of angina and no history of recent use of contraceptive drugs can be regarded as favorable features to anticipate a pregnancy without serious complications. Before undertaking pregnancy, full investigation, including coronary arteriography, should be undertaken. DISSECTING

ANEURYSM

OF THE AORTA

It is well recognized that the state of pregnancy is a predisposing factor in the development of aortic dissections2, 138 During pregnancy, structural changes occur in the walls of large arteries, including the aorta, which are instrumental in the causation of dissection.s In a study of 49 cases of aortic dissection in women of childbearing age, 24 (49%) occurred in association with pregnancy.S2 The strain of labor did not appear to be an important factor in the causation of dissection, since 20 of the 24 cases occurred before the onset of labor. The clinical picture is variable and depends on the extent of the dissection. The presenting symptoms and signs may be predominantly cardiovascular, gastrointestinal or neurologic in nature. Dissection of the aorta is usually associated with arterial hypertension and there is also an increased liability to dissection in patients with coarctation of the aorta. In the patient reported by Hume and Krosnick,13s who had no hypertension or coarctation, dissection occurred at the onset of labor, and the lesion was surgically repaired after delivery by cesarean section. Aortic dissection is also an important complication of Marfan’s syndrome. Husebye et a1.140 reported the case of a 22-year-old woman with Marfan’s disease who had had repeated episodes of aortic dissection between the 22d and 31st weeks of gestation. She was delivered of a normal infant by cesarean section at 38 weeks. However, the patient died of congestive heart failure 8 months later. In a study of 15 cases of fatal aortic dissection in pregnant patients, 9 were considered to have definite Marfan’s disease and 4 more had suggestive evidence of this disorder.141 The patient with Marfan’s disease reported by Elias and Berkowitz14* had 2 uncomplicated pregnancies, but only one child was normal, the other had signs of Marfan’s syndrome. Her 3d pregnancy was terminated. The management of aortic dissection occurring during preg61

nancy is conducted on the same lines as in the nonpregnant state. Prompt control of the hypertensive state, if present, should be attempted, but it cannot be too strongly emphasized that lowering-of the blood pressure, even to an “acceptable” level, is not an abgolute safeguard against aortic rupture. Complete prolonged bed rest is essential. Surgery has an important part to play in this condition, either as an immediate emergency measure or at a later stage, if after survival of the acute episode the disease shows signs of progression. PRIMARY PULMONARY HYPERTENSION The term primary pulmonary hypertension has been retained, but this syndrome is being discussed outside the section on congenital cardiovascular disease because its existence as a congenital entity has been questioned. 143Although a congenital abnormality of the media of the small pulmonary arteries has been considered an etiologic factor144 and a familial incidence has also been well documented,145 it has been suggested that in a large number of cases of so-called primary pulmonary hypertension, the process starts later in life with the development of multiple miliary pulmonary emboli provoking a vascular reaction.146 The disease involves predominantly young women. Its natural course, which terminates either by sudden death or by the development of congestive heart failure, is hardly influenced by the administration of vasodilating agents or anticoagulants. Pregnancy is a serious undertaking in primary pulmonary hypertension as a maternal mortality of up to 53% has been recorded.*l The mode of death is syncope rather than progressive right heart failure, just as in severe pulmonary hypertension as part of the Eisenmenger’s syndrome. In view of the high maternal risk, patients with primary pulmonary hypertension should be advised against becoming pregnant. As the use of oral contraceptive agents carries an increased risk in this condition, appropriate counseling should be considered. If a patient with this disorder is found to be pregnant, serious consideration should be given to termination of the pregnancy. If termination is not feasible, the patient should be encouraged to have periods of prolonged rest, but not in the supine position for any length of time in order not to exaggerate the tendency to syncope in susceptible cases. As labor and the immediate postdelivery time are the most critical periods, any excessive blood loss should be controlled without delay. The maintenance of the systolic blood pressure at a satisfactory level is an essential requirement. Undue physical effort should be avoided at any time throughout pregnancy. Continuous drug therapy, including the use of oral anticoagulants, has little part to play in the management of these patients during pregnancy. 62

THE USE OF DRUGS AND OTHER AGENTS IN PREGNANCY Most of the drugs administered to women during pregnancy are liable to cross the placental circulation and some of these create a potential hazard to the fetus. This point is to be considered in all stages of pregnancy, but the most critical periods are the 1st trimester, when organogenesis takes place, and late pregnancy near term. In treating maternal disorders, it is necessary to weigh the beneficial action of any drug used against its potential adverse effect on the fetus. In the present section we shall only discuss the effects of commonly used drugs in cardiovascular practice. DIGITALIS. - Transplacental transmission of digitalis has been fully documented. 14’ However, maternal digitalis therapy is virtually safe from the point of view of fetal well-being. Considering the very large number of pregnant women who have been receiving digitalis over the years, there is a striking paucity of episodes of even suggestive digitalis-induced cardiotoxicity in the newborn. In one case, ingestion of a “large” dose of digitoxin by the mother in the 8th month of her pregnancy and 4 days before delivery was considered to be responsible for the ECG changes of ST-segment depression and atrioventricular conduction defect in the newborn. 14* In an unselected series of ECG cardiograms in more than 50 newborn infants of mothers who received digitalis during pregnancy, the only abnormality we have encountered was a junctional rhythm on one occasion, which persisted for 48 hours. Mendelson31 has also emphasized the virtual absence of clinical or ECG evidence of digitalis cardiotoxicity in infants born to mothers who had received digitalis throughout pregnancy. Rogers et a1.14’ measured digitalis concentrations in the fetal umbilical cord by radioimmunoassay and found that it was similar to that in the maternal venous blood. They also made the interesting observation that a relatively low maternal serum digoxin level toward the end of pregnancy can increase after delivery without any change in the digitalis dosage. The authors raised the possibility that the fetus participates in the metabolism of digitalis. It is also of interest that spontaneous labor was found to occur earlier and was shorter in patients who were taking digitalis as compared with a group of patients not receiving digitalis.14s This effect has been attributed to the direct action of digitalis on the myometrium. DIURETICS. -With the exception of thiazides, which may cause liver damage and neutropenia in the fetus, the main diuretics currently in use have not been observed to cause any adverse effects on the fetus.150 In any event, there is now general agreement that diuretics should be used sparingly during pregnancy, 63

perhaps only in severe water retention, because of their potential undesirable effects on maternal hemodynamics. CORTICOSTEROIDS.-There is some evidence that the use of steroids in pregnancy may result in placental insufficiency and increase in perinatal mortality. 151*152However, the risk appears to be rather small and should not constitute an absolute bar to the use of steroids in urgent cases in which there is good indication for such therapy. . SALICYLATES. - Salicylates administered to the mother during the late stages of pregnancy may be responsible for hemorrhagic events in the newborn because of platelet dysfunction and low factor XII concentrations in the fetus.152 ANTICOAGULANTS. -The potential hazards of bleeding and of teratogenic effects of oral anticoagulants have been fully discussed in the section on the use of anticoagulants in pregnancy. ANTIBIOTICS.-Most antibiotics, if not all, readily cross the placental circulation. Experience would indicate that penicillins as a group are virtually safe and have no adverse effect on the fetus. However, some other antimicrobial drugs can be responsible for selective adverse effects on the newborn. Some of the sulphonamides may prevent the inactivation of bilirubin by competing with it for binding on plasma proteins and thus leading to a rise in free bilirubin plasma concentration with its consequences.l52> l53 Streptomycin and related antibiotics may damage the 8th cranial nerve of the fetus, especially if given for longer periods during pregnancy. 154 Tetracyclines are known to cause staining of deciduous teeth in the newborn and also depression of bone growth, possibly through the process of chelation with calcium. SEDATIVES AND ANALGESICS.-Barbiturates and other sedatives, as well as morphine can cause depression of the respiratory center in the newborn, if given to the mother during labor. Morphine can also reduce significantly the fetal heart rate. 155 ANTIARRHYTHMIC AGENTS. -On the whole, currently used antiarrhythmic drugs can be safely given to pregnant patients. However, phenytoin, which is used in cardiologic practice as an antiarrhythmic agent, has been reported to cause occasionally congenital heart defects and cleft lip and/or cleft palate. 156 /3-ADRENERGIC BLOCKING AGENTS. -p-Blockers have been most successfully used as antiarrhythmic, antianginal and antihypertensive agents and have accordingly a definite place in the management of certain pregnant patients. However, their use in pregnancy can result in adverse effects on the fetus. These side effects have been discussed in the section on hypertensive disorders. 64

EFFECTS OF MATERNAL SMOKING ON THE FETUS.-There is suggestive evidence that mothers who smoke during pregnancy have smaller infants than those who do not smoke. It has been reported that smoking has resulted in enlargement of the placenta, with microscopic changes such as obliterative endarte?itis and necrosis of the decidua basalis.15’ The placental changes were considered to be the result of underperfusion caused by a reduced uterine blood flow. The undesirable effect of smoking is also illustrated by the observations that in pregnant women who stopped smoking in the 3d trimester for 48 hours there was a reduction in carboxyhemoglobin and a decrease in hemoglobin-oxygen affinity, resulting in an increase of 8% in oxygen availability in the 48 hours.15* There is no conclusive direct evidence that maternal smoking has teratogenic effects on the fetus.159 MATERNAL ALCOHOL CONSUMPTION. -A syndrome referred to as fetal alcohol syndrome has been described to occur in the offspring of some alcoholic mothers.lGO, 16’ The main features are growth retardation, characteristic facial features and congenital heart defects.

OxvToc~c AGENTS.-In spite of scanty reports of acute pulmonary edema following the administration of ergometrine, we believe that its use can be made safe in the presence of organic heart disease. This opinion was recently reemphasized by de Swiet,l@ who also suggested that patients who may be considered at risk can be given simultaneously a rapidly acting parenteral diuretic or diazepam, which neutralizes to some extent the effect of ergometrine on the central venous pressure. DRUGS AND BREAST-FEEDING.-There is insufficient information as yet on the potential adverse effects on the suckling infant of most drugs taken by the mother during pregnancy and after delivery. However, current experience confirms the view that digitalis and warfarin can be safely taken by the breast-feeding women, In the case of other drugs, great caution should be exercised. A high therapeutic ratio is not an absolute guarantee that the drug is safe and cannot have adverse effects.

INDICATIONS

FOR TERMINATION

OF PREGNANCY

Precise medical indications for the therapeutic termination of pregnancy cannot be formulated on a generally agreed basis. Furthermore, changing social attitudes in many countries have tended to obscure the sharp dividing line between medical indication in its strictest sense and social indication. However, individual workers or group of workers can propose certain guidelines taking into account their own personal medical experience and external conditions they are confronted with in their prac65

tice. Admittedly, even these guidelines have to remain flexible in order to accommodate specific situations. We believe that in rheumatic heart disease, therapeutic terminations of pregnancy is hardly ever necessary on strictly medical grounds. The &lidity of this approach became evident to us even before the introduction of cardiac surgery. Today we think that our opinion requires no revision; indeed, it is further strengthened by the successful results achieved by cardiac surgery in the types of cases of rheumatic heart disease that are likely to be encountered in pregnancy. Patients with cyanotic congenital heart disease that is amenable to cardiac surgery but remains yet uncorrected run an increased risk on becoming pregnant. In case of cardiocirculatory failure, medical treatment is often ineffective and cardiac surgery performed under these circumstances in pregnancy is associated with a greatly increased risk. Accordingly, termination of pregnancy should be seriously considered as early as possible. These patients have a very good chance of negotiating successfully one or more future pregnancies after surgical correction of the cardiac defect. Patients with primary pulmonary hypertension and those with severe pulmonary hypertension as an integral feature of the Eisenmenger syndrome constitute a high-risk group. As stated before, these patients should be advised to avoid becoming pregnant and in those found to be pregnant, early termination of the pregnancy should be strongly recommended. THE IMPORTANCE OF PREGRAVIDITY ASSESSMENT THE CARDIAC STATE. ADVICE ON UNDERTAKING PREGNANCY OR CONTRACEPTION.

OF

Current health care, whether within the framework of a full or partial national health service or of any other system, provides for routine medical examination at birth, at school age and in most cases at the start of employment. Thus, most women, if not all, are likely to be aware of any cardiovascular disorder they may have before contemplating to undertake their first pregnancy. We refer here only to the cardiovascular system, but obviously other medical disorders require similar considerations. In this way, attendances at antenatal clinics have gradually become less and less important occasions for “case finding” purposes. Broadly speaking, assessment of the cardiovascular state prior to pregnancy would place the women into one of 3 groups, i.e., (1) those with a normal cardiovascular system, who require no special attention; (2) those with organic heart disease, but (a) unlikely to require specific therapeutic action in the near or foreseeable future, or (b) with symptoms and/or signs indicating the 66

desirability of early therapeutic action before a final opinion is expressed regarding fitness for pregnancy; and (3) those with organic heart disease the nature of which would render pregnancy inadvisable on account of its progressive course and nonamenability to surgical correction. There are a number of examples to illustrate the situation of patients in group 2b. One such important example is the young woman who is entirely symptom-free but has unmistakable signs of severe mitral stenosis. Considering the currently very low risk of closed mitral valvotomy, we would advise cardiac surgery in such a patient before undertaking pregnancy. A similar surgical approach may be considered in the presence of uncorrected congenital heart disease, but the decision depends on the nature of the cardiac defect. The institution of antihypertensive drug therapy should be considered in patients with so far untreated and perhaps only moderate essential hypertension. Patients in group 3 present a serious problem. Statistically, they run a serious risk on becoming pregnant since the maternal mortality rate is high; however, uneventful pregnancies have been observed in a large number of cases. Accordingly, a more individualized approach, taking into account all medical and environmental factors, is the only rational procedure. Should the advice be against pregnancy, further counseling with a view to avoiding pregnancy is an integral part of medical care. In general, the use of oral contraceptive agents is associated with some risk, even in apparently healthy women. In the presence of cardiovascular disease, the risk is greatly increased and in some cases it may be prohibitive. The main cardiovascular risk is venous thrombosis, which often gives rise to pulmonary embolization. However, since the reduction of the estrogen content of the commonly used contraceptive agents, the incidence of venous thrombosis and of pulmonary embolism has declined.lG3 Other important complications likely to be related to the use of oral contraceptive agents are cerebrovascular disease, including subarachnoid hemorrhage, and myocardial infarction.131, 164 In young women taking oral contraceptive agents who developed transmural myocardial infarction there was evidence of reduced coronary flow in the presence of normal, unobstructed coronary arteries.*64 If the nature of the cardiac disease is such that the risk of using oral contraceptive agents is considered prohibitive, alternative methods of contraception may have to be adopted on a temporary or permanent basis. However, sterilization of the woman or vasectomy in the husband are measures that should not be lightly undertaken and that require the most meticulous consideration of all medical, social and environmental factors pertaining to the case. 67

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