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Pregnancy in the presence of tetralogy of Fallot
Pregnancy
in the Presence
of Tetralogy
of Fallot Observations EPHRAIM C. MEYER,
on Two Patients*
S. TULSKY, M.D., PETER SIGMANN, M.D. and EARL N. SILBER, M.D.
M.D., ALEX
Chicago,
A
Illinois
this hospital at the age of 10 following a cyanotic syncopal episode. Clinical evaluation was consistent with tetralogy of Fallot with a moderate bidirectional shunt. A small and late pulmonic component of the second sound was heard and recorded (Fig. 1). The electrocardiogram showed peaked P waves in
TOTAL of 55 pregnancies in 46 patients with tetralogy bf Fallot have been reported;‘” but in over half of them the precise nature of the lesion has not been unequivocally established. With the advent of shunt procedures, the prognosis has been improved, and the hemodynamic changes induced by pregnancy have been altered. The functional size of the shunt produced will have a bearing on the degree of the eventual volume load of the left ventricle. The patients are exposed to the risk of shunt reversal and marked arterial unsaturation should systemic resistance fall precipitously during pregnancy or labor.‘v6 These facts were born out in successful pregnancies in two patients with hemodynamically proved tetralogy of Fallot. Analysis of these 2 cases revealed certain other interesting phenomena.
lead II and in the left precordial leads; QRS was mainly inverted in leads I, aVL and in leads from the left precordium, and mainly upright in lead VI. The tracing was interpreted as an “adaptation type” of right ventricular hypertrophy. Right heart catheterization revealed pressures of 90/5 mm. Hg in both ventricles and a systolic gradient of 80 mm. across the pulmonic valve with infundibular and valvular components. Communications between the right and the left side at both atrial and ventricular levels appeared to be present. At the age of 13, selective angiocardiography established the diagnosis of tetralogy of Fallot, and an additional atria1 defect was ruled out. Several x-ray studies throughout the years revealed only slight cardiomegaly. The patient was well developed, falling consistently into the fortieth percentile in weight and height. Course During Pregnancy: The patient was closely observed from her initial admission during pregnancy until term. Oral iron and vitamin preparations were prescribed, but she needed no digitalis. The pertinent laboratory data are charted in Table I and Figure 2. In the initial 20 weeks of gestation a progressive reduction of effort tolerance was obAlthough no overt signs of congestive heart served. failure were noted, venous pressure was elevated. The laboratory tests revealed essentially a reduced arterial oxygen saturation and a fall in hematocrit with an increased plasma volume as determined by tagged albumin technic. In the phonocardiogram a single second sound was recorded, suggesting reduced blood flow across the pulmonic valve (Fig. 1). Although further deterioration was expected during
CASE REPORTS CASE 1. A 16 year old Negro girl was admitted to Michael Reese Hospital on May 21, 1963 after an episode of lightheadedness. A 12 week old pregnancy was found on examination of this cyanotic patient. She was referred to the Obstetric Service for further evaluation. This patient had been followed-up by us for the past six years. Cyanosis of the lips and choking during feedings had been reported in the first year of her life. Motor development was moderately retarded; she sat when 10 months old and did not stand before 22 months. At the age of 3 years definite cyanosis, marked fatigability and squatting were noted. She was admitted to another hospital at the age of 5 where cardiomegaly and a normal hemogram were reported. Findings Prior to Pregnancy: She was first admitted to
* Fram the Cardiovascular Institute and the Department of Obstetrics and Gynecology, Michael Reese Hospital and Medical Center, Chicago, Ill. This study was supported by grants of the National Heart Institute (HE-06375 and HTS-5252). 874
THE
AMERICAN
JOURNAL
OF CARDIOLOGY
Pregnancy and Tetralogy of Fallot 5-s-62,
6EF0RE
PREGNANCY
875 5-25-68
FRYH WEEK
a6lH
WEEK
7-19-u OF
OF
PREGNANCY
PREGNANCY
FIG. 1. Case 1. Phonocardiograms. Tracing at upper left (5/5/62)
taken before pregnancy at paper speed of 100 mm./sec., showing a late pulmonic component of the second sound (Ps). The tracing recorded during the eighteenth week of gestation (May 25, 1963) at paper speed of 50 mm./sec., reveals a single second sound, whereas in the sound records later in pregnancy (twenty-sixth week) and four weeks post partum the pulmonary component of the second sound reappears.
the latter part of pregnancy, the patient improved; she was less fatigued and tolerated her pregnancy well. Venous pressure dropped, and the arterial oxygen saturation rose moderately. The hematocrit, despite the dilution effect of pregnancy, rose from 48 per cent in the twentieth week to 60 per cent at term. During the latter part of pregnancy a late and small
pulmonary component of the second sound reappeared (Fig. 1.). The patient had an uneventful delivery in the thirtieth week of pregnancy and gave birth to a small, normal female child. Five hours post partnm a short episode of syncope occurred with marked cyanosis and no measurable blood pressure. This episode was successfully treated by vasopressor
TABLE I Case 1.
Laboratory
Data Before, During and Following Pregnancy ----Pregnancy
7-
Hemoglobin (gm. %) Hematocrit (%) cells (millions/mma.) Arterial oxygen saturation (%) Venous pressure (mm. saline) Circulation time, arm to mouth (sec.)
Redblood
VOLUME
14,
DECEMBER
1964
(Weeks)
(Delivery Nov. lo,1963
1960
1962
14
16
20
24
26
28
32
34
36
38
Partum
20.0
17.8
17.3
15.5 50
15.5 48 5.2 75 190 1s
17.0 54 5.5
16.0 52
17.8 55 6.0 82
17.6 54 ._.
16.8
18.8 60 7.1
16.8 52
120 20
. . .
18.6 58 6.4 82 140 22
:: : 80
.
::: . .
a.b
.
.
73
5.6
86
Meyer,
876
Tulsky? Sigmann
and Silber
JO I.
45
110
[I Yen. cm.
on f
i-
Press.
I5
Saline
10 f-
Heart
Sound.
Sl L-.
time
1 rh P
20th
8eforcl
26th
32nd
3f3th
JAfta,
Pregnonry
FIG. 2. Case 1. Laboratory data before, during and following pregnancy. Note the tendency for dilution of blood in the initial 20 weeks which is reversed later in
pregnancy.
agents. The patient at the time of this report was scheduled for complete surgical correction of her lesion. CASE 2: This 21 year old white woman in her twenty-fifth week of pregnancy was known to have been a “blue baby” since her first year of life. At the age of 9 she was admitted to another hospital and found to be cyanotic at rest and dyspneic on moderate effort. The clinical, electrocardiographic and x-ray studies were reported to be consistent with tetralogy of Fallot. Right heart catheterization and angiocardiography confirmed this clinical impression. A
left-sided Potts’ operation was performed at this time. Cyanosis disappeared. At the age of 18 the patient maintained normal activity and was not cyanotic. X-ray films revealed moderate cardiomegaly with heavy vascular markings in the left lung field. The electrocardiogram showed evidence of left atria1 and left ventricular enlargement in addition to right ventricular hypertrophy. At the age of 21 the patient was followed-up She was digitalied and throughout her pregnancy. started on diuretic therapy prophylactically during the twenty-thiid week of pregnancy. Although no objective cause for her complaints of dyspnea, orthopTHE
AMERICAN
JOURNAL
OF
CARDIOLOQY
Pregnancy
and Tetralogy
877
of Fallot
vital capacity remained consistently in the range of predicted values. In the thirty-ninth week of gestation the patient was delivered uneventfully of a 5 lb. 12 oz. male child. The postpartum period was uncomplicated. Digitalization and diuretic therapy were stopped three months post partum. The patient has remained well except for recurrent bouts of paroxysmal atria1 tachycardia, for the control of which redigitalization and quinidine administration have been necessary.
DISCUSSION AVR
AVL
AVF
Vl
V2
V3
V4
Vs
V6
Case 2. Electrocardiogramrevealing left ventricular hypertrophy and strain with no associated features of right ventricular hypertrophy 11 years following an aortopulmonary shunt operation. There is a vertical position and digitalis alteration of the ST-T segment.
FIG. 3.
nea and palpitation was found, she was admitted to Michael Reese Hospital for further evaluation in her twenty-fifth week of gestation. On admission, the patient had no overt signs of heart failure; her lungs were clear; liver and spleen were not enlarged ; her neck veins were not engorged and only minimal ankle edema was present. The precordium was hyperactive with apical impulse palpable 2 cm. lateral to the midclavicular line as an accentuated and sustained heave. Blood pressure was 1601 50 mm. Hg, and the peripheral pulses were collapsing. An early ejection murmur closely followed the first sound ; the second sound was widely split with a small and late pulmonic component. A third sound was heard at the apex followed by a short diastolic flow murmur. In the pulmonic area a continuous machinery murmur was heard, and in the third intercostal space a loud, widely radiating systolic ejection murmur was present. The electrocardiogram revealed left ventricular hypertrophy and strain with no associated features of right ventricular hypertrophy (Fig. 3). Venous pressure was 143 mm. of saline and the circulation time (arm to tongue) was 14 sec. The patient was discharged, and the latter part of pregnancy was uneventful. Serial measurements of VOLUME14, DECEMBER1964
These 2 cases confirm the view that pregnancy is compatible with tetralogy of Fallot. Both patients were definitely proved by phonocardiography and by hemodynamic and other laboratory data to have tetralogy of Fallot. In only 20 of 46 patients previously reported was the diagnosis confirmed by such studies or by subsequent autopsy. Cyanosis, per se, does not represent a contraindication to pregnancy.5 Thus, among the 55 pregnancies previously reported, the over-all fetal mortality was 22, and maternal mortality, 7. There were 2 fetal losses and no maternal mortality in 9 of the patients who had shunt procedures prior to pregnancy. Both our patients carried their pregnancy without serious complication to both mother and child. The prognosis of mother and fetus has been related to the maternal hematocrit. In the presence of maternal bulboconal malformation, Neill’ found a fetal mortality of 85 per cent when the hematocrit exceeded 65 per cent, and 60 per cent with less severe hematocrit elevations. The problem of appropriate hematocrit in these circumstances is made more complex by the observation that patients with congenital cyanotic heart disease with elevated hematocrits may have hypochromic cells, suffer from relative anemia and require iron therapy.8 Shunt procedures have not only improved the prognosis, but also have altered the pathophysiology and, hence, the course of tetralogy of Fallot during pregnancy. The fraction of cardiac output shunted in tetralogy of Fallot, with a given size of a ventricular septal defect, is determined by the difference between the effective resistance offered by the peripheral arteries and that of the fixed obstruction at the pulmonic valve. This fraction, in turn, determines the arterial oxygen saturation which, presumably, determines the amount of stimulation of the hemopoietic system to vary both the relative and absolute volume change in the red blood
878
Meyer,
‘Fulsky,
cells. The increased blood viscosity in patients with this disease is due to the crythrocytosis so engendered. 9,liJ The phy’siologtr~ alterations induced by fvrgnancy produce a fall in the systemic perilhera resistance in two way.9~“~‘“: 1. By increasing plasma volume (40 to 50y0) in excess of the increase in red cell volume (20 to 3Ooj,), a hemodilution and lower viscosity result. This increase in plasma volume appears in the twelfth week of gestation and gradually increases until the twenty-fourth week, after which the rise is accelerated to reach a peak about the thirty-third week.12-16 2. The placenta, by behaving hemodynamically as an arteriovenous fistula,’ leads to a shunt effect. During the last month of pregnancy this action of the placenta declines. A pregnant patient with tetralogy of Fallot should, like the normal patient, have a similar placental shunting during the course of pregnancy. The reduced peripheral resistance in turn would lead to a progressively greater fraction of blood being shunted from the right to the left side of the heart.2r6 Pregnancy and Blood Viscosity: We assume that plasma volume rose in our patients, as expected, throughout pregnancy. This initially aggravated the disease in our first case, as documented by a rise in venous pressure, a drop in the arterial oxygen saturation and a dilution effect with the hematocrit approaching normal levels. Her unexpected clinical improvement in the latter half of pregnancy was associated with a rise in hematocrit which represented an almost twofold increase in the relative viscosity of the Because of the lack of homogeneity of blood.g the blood and the size of the capillaries it traverses, the effect of viscosity on resistance to flow cannot be approximated by Poiseuille’s law alone.‘6 Resistance across the pulmonic obstruction depends on whether flow is laminar However, there is some experior turbulent.” mental evidence that resistance rises with relative increase in viscosity in the hind legs of Thus, the effects of increased viscosity dogs.ls in tetralogy of Fallot are complex and matheNevertheless, it is posmatically unsolvable. sible that increased viscosity raised the resistance in the peripheral vascular bed significantly more than in the region of the relatively short and wide pulmonary valve. The result, if this were true, would be to reduce right to left shunt and even to enhance pulmonary flow in the latter part of pregnancy. This hypothesis
Sigmatln
and Silber
to ‘Iccount for our clinical observations is supported b!, the reappearance of the pulmonary component of the second sound in the phonocardiogram after having been absent in a sound tracing during the eighteenth week of gestation (,Fig. l).lg Analogous animal experiments should test this hypothesis. Pregnanry Following Shunt Procedure for TetralOgY: Our second case exemplifies one possible result in a patient following a shunt procedure. The hemodynamic status is altered by the operation which simulates a large patent ductus arteriosus with a significant left to right shunt. Consequently, there is an augmented volume load on the left ventricle. The electrocardiogram shows a striking evolution from a pattern of right ventricular hypertrophy to that of left ventricular hypertrophy and strain. Long term follow-up after shunt procedures20-23 in nearly 2,000 patients with tetralogy of Fallot reveals that moderate enlargement of the cardiac silhouette is common and is to be considered a manifestation of augmented volume load. In one series,*O combined ventricular hypertrophy was observed in two thirds of all patients 10 years after surgery. A more advanced evolution of the electrocardiogram, as seen in our second case, however, has not been mentioned. In one report,23 the possibility of left ventricular failure was mentioned but not documented. The relative resistance across the surgically induced defect will determine the size and direction of the shunt. In tetralogy of Fallot, a connection is created between a normal arterial vascular bed and pulmonary circulation “protected” by the obstruction at the pulmonic outflow tract. The resistance of the surgically induced defect itself, added to a possible functional constriction of the pulmonary vessels, prevents a massive left to right shunt. However, when the surgical shunt becomes large and the inherent resistance, therefore, becomes low, left ventricular failure due to volume overload may result. A reversal of the surgical shunt seems unlikely. However, increased shunting from right to left may occur in the interventricular defect inasmuch as the resistance of the fixed obstruction at the pulmonary outflow tract exceeds, in these patients, the systemic peripheral resistance. The variability of the latter in pregnancy, labor and the immediate postpartum period, for instance, are marked. The dramatic consequences of systemic hypotension seen in our first patient following delivTHE
AMERICAN
JOURNAL
OF
CARDIOLOGY
Pregnancy
and Tetralogy
ery, have been documented in a case reported by Hamiltonz3 in which the right to left shunt presumably varied between 100 per cent and zero as the arterial oxygen saturations increased from 15 per cent when the blood pressure was 65/30 mm. Hg to 85 per cent with a blood pressureof 165/110. Analysis of other patients with tetralogy of Fallot during pregnancy, as made by us in these two cases, may lend further support to our interpretations. SUMMARY
Two patients in their first pregnancy and with tetralogy of Fallot, proved by cardiac catheterization and angiocardiography, are Both delivered successfully at term. presented. In the first patient, age 16, the red blood cell count, hematocrit, arterial oxygen saturation and phonocardiogram had been examined frequently. A striking clinical improvement in the latter half of the pregnancy accompanied a rise of the hematocrit from 48 to 60 per cent. The pulmonic component of the second heart sound disappeared in the second trimester but was again recorded in the third, when the red These blood cell concentration was again high. data are discussed with special consideration of the role played by increased blood viscosity in the last trimester. The second patient, now 21 years old, had an augmented left ventricular volume load due to a Potts’ operation 11 years earlier. The possible effects of this type of surgical intervention on patients with tetralogy of Fallot during pregnancy are discussed.
5.
6.
7.
8.
9.
10.
11. 12.
13.
14.
15.
16. 17. 18.
19. ACKNOWLEDGMENTS We are indebted to Dr. Louis N. Katz for his advice in preparing this report.
20.
REFERENCES 1. BURWELL, C. S. and METCALPE, J. Heart Diseases in Pregnancy, pp. 26 and 207. Boston, 1937. Little, Brown and Co. 2. MENDELSON,C. L. Cardiac Diseases in Pregnancy, p. 156. Philadelphia, 1960. F. A. Davis Co. 3. EASTMAN,N. Editorial. Obst. Gynec. Survey, 12 : 487, 1957. 4. BAKER, J. L. et al. Closed pulmonary valvulotomy
VOLUME
14,
DECEMBER
1964
21. 22. 23.
of Fallot
879
in the management of Fallot’s tetralogy complicated by pregnancy. J. Obst. & Gynaec. Brit. Comm., 70: 154, 1963. BARNES, A. C. and REID, D. E. Discussion in: CANNEL, D. E. and VERNON, C. P. Congenital heart disease and pregnancy. Am. J. Obst. & Gynec., 85: 744, 1963. HYLAND, J. W. Discussion in: COPELAND,W. E., WOOLEY, C. F., RYAN, J. M., RUNCO, V. and LEVIN, H. S. Pregnancy and congenital heart disease. Am. J. Obst. f_%? Gym-c., 86: 107, 1963. NEILL, C. A. and SWANSON,S. Outcome of pregnancy in congenital heart disease (Abstr.). Circulation, 24: 1003, 1963. RUDOLPH, A. M., NADAS, A. S. and BORGES,W. H. Hematologic adjustment to cyanotic congenital heart disease. Pediatrics, 11: 454, 1953. PIROFSKY, B. The determination of blood viscosity in man by a method based on Poiseuille’s law. J. Clin. Invest., 32: 292, 1953. NELSON, W., MAYERSON, H. S., CLARK, J. H. and LYONS, C. Blood volume in congenital heart disease. J. Clin. Invest., 28: 860, 1947. ADAMS, J. Q. Cardiovascular physiology in normal pregnancy. Am. J. Obst. & Gynec., 67: 741, 1954. COHEN, M. E. and THOMSON, K. J. Studies on the circulation in pregnancy. J.A.M.A., 112: 1556, 1939. BERLIN, N. I., GOETSCH,C., HYDE, G. M. and PAX+ SONS, R. J. The blood volume in pregnancy. Surg. Gynec. & Obst., 97: 173, 1953. KELLAR, R. J. Toxemias of Pregnancy. In: Ciba Foundation Symposium, p. 135. Philadelphia, 1950. Blakiston Co. DIECKMANN,W. J. and WECENER, C. R. Studies of the blood in pregnancy. Arch. Znt. Med., 53: 71, 188,353,1934. GREEN, H. D. Medical Physics, Vol. II, p. 238. Chicago, 1950. Year Book Publishers. WITTAKER, S. R. and WINTON, F. R. The viscosity of blood. J. Physiol., 78: 338, 1933. VOGELPOEL,L. and SCHIURE,V. Auscultatory and phonocardiographic assessment of Fallot’s tetralogy. Circulation, 22: 73, 1960. PAUL, M. H., MILLER, R. A. and POTTS, W. J. Long term results of aortic-pulmonary anastomosis for tetralogy of Fallot. Circulation, 23: 525, 1961. TAUSSIC, H. B. and BAUERSFELD,S. R. Follow-up studies on first 1,000 patients operated on for pulmonary stenosis or atresia. Ann. Znt. Med., 38: 1, 1953. CAMPBELL,M. Late results of operations for Fallot’s tetralogy. Brit. M. J., 2: 1175, 1958. NADAS, A. S. Pediatric Cardiology, p. 656. Philadelphia, 1963. W. B. Saunders Co. HAMILTON, W. F., WINSLOW, J. A. and HAMILTON, W. F., JR. Notes on a case of congenital heart disease with cyanotic episodes. J. Clin. Invest. 29: 20, 1950.
in the Presence
of Tetralogy
of Fallot Observations EPHRAIM C. MEYER,
on Two Patients*
S. TULSKY, M.D., PETER SIGMANN, M.D. and EARL N. SILBER, M.D.
M.D., ALEX
Chicago,
A
Illinois
this hospital at the age of 10 following a cyanotic syncopal episode. Clinical evaluation was consistent with tetralogy of Fallot with a moderate bidirectional shunt. A small and late pulmonic component of the second sound was heard and recorded (Fig. 1). The electrocardiogram showed peaked P waves in
TOTAL of 55 pregnancies in 46 patients with tetralogy bf Fallot have been reported;‘” but in over half of them the precise nature of the lesion has not been unequivocally established. With the advent of shunt procedures, the prognosis has been improved, and the hemodynamic changes induced by pregnancy have been altered. The functional size of the shunt produced will have a bearing on the degree of the eventual volume load of the left ventricle. The patients are exposed to the risk of shunt reversal and marked arterial unsaturation should systemic resistance fall precipitously during pregnancy or labor.‘v6 These facts were born out in successful pregnancies in two patients with hemodynamically proved tetralogy of Fallot. Analysis of these 2 cases revealed certain other interesting phenomena.
lead II and in the left precordial leads; QRS was mainly inverted in leads I, aVL and in leads from the left precordium, and mainly upright in lead VI. The tracing was interpreted as an “adaptation type” of right ventricular hypertrophy. Right heart catheterization revealed pressures of 90/5 mm. Hg in both ventricles and a systolic gradient of 80 mm. across the pulmonic valve with infundibular and valvular components. Communications between the right and the left side at both atrial and ventricular levels appeared to be present. At the age of 13, selective angiocardiography established the diagnosis of tetralogy of Fallot, and an additional atria1 defect was ruled out. Several x-ray studies throughout the years revealed only slight cardiomegaly. The patient was well developed, falling consistently into the fortieth percentile in weight and height. Course During Pregnancy: The patient was closely observed from her initial admission during pregnancy until term. Oral iron and vitamin preparations were prescribed, but she needed no digitalis. The pertinent laboratory data are charted in Table I and Figure 2. In the initial 20 weeks of gestation a progressive reduction of effort tolerance was obAlthough no overt signs of congestive heart served. failure were noted, venous pressure was elevated. The laboratory tests revealed essentially a reduced arterial oxygen saturation and a fall in hematocrit with an increased plasma volume as determined by tagged albumin technic. In the phonocardiogram a single second sound was recorded, suggesting reduced blood flow across the pulmonic valve (Fig. 1). Although further deterioration was expected during
CASE REPORTS CASE 1. A 16 year old Negro girl was admitted to Michael Reese Hospital on May 21, 1963 after an episode of lightheadedness. A 12 week old pregnancy was found on examination of this cyanotic patient. She was referred to the Obstetric Service for further evaluation. This patient had been followed-up by us for the past six years. Cyanosis of the lips and choking during feedings had been reported in the first year of her life. Motor development was moderately retarded; she sat when 10 months old and did not stand before 22 months. At the age of 3 years definite cyanosis, marked fatigability and squatting were noted. She was admitted to another hospital at the age of 5 where cardiomegaly and a normal hemogram were reported. Findings Prior to Pregnancy: She was first admitted to
* Fram the Cardiovascular Institute and the Department of Obstetrics and Gynecology, Michael Reese Hospital and Medical Center, Chicago, Ill. This study was supported by grants of the National Heart Institute (HE-06375 and HTS-5252). 874
THE
AMERICAN
JOURNAL
OF CARDIOLOGY
Pregnancy and Tetralogy of Fallot 5-s-62,
6EF0RE
PREGNANCY
875 5-25-68
FRYH WEEK
a6lH
WEEK
7-19-u OF
OF
PREGNANCY
PREGNANCY
FIG. 1. Case 1. Phonocardiograms. Tracing at upper left (5/5/62)
taken before pregnancy at paper speed of 100 mm./sec., showing a late pulmonic component of the second sound (Ps). The tracing recorded during the eighteenth week of gestation (May 25, 1963) at paper speed of 50 mm./sec., reveals a single second sound, whereas in the sound records later in pregnancy (twenty-sixth week) and four weeks post partum the pulmonary component of the second sound reappears.
the latter part of pregnancy, the patient improved; she was less fatigued and tolerated her pregnancy well. Venous pressure dropped, and the arterial oxygen saturation rose moderately. The hematocrit, despite the dilution effect of pregnancy, rose from 48 per cent in the twentieth week to 60 per cent at term. During the latter part of pregnancy a late and small
pulmonary component of the second sound reappeared (Fig. 1.). The patient had an uneventful delivery in the thirtieth week of pregnancy and gave birth to a small, normal female child. Five hours post partnm a short episode of syncope occurred with marked cyanosis and no measurable blood pressure. This episode was successfully treated by vasopressor
TABLE I Case 1.
Laboratory
Data Before, During and Following Pregnancy ----Pregnancy
7-
Hemoglobin (gm. %) Hematocrit (%) cells (millions/mma.) Arterial oxygen saturation (%) Venous pressure (mm. saline) Circulation time, arm to mouth (sec.)
Redblood
VOLUME
14,
DECEMBER
1964
(Weeks)
(Delivery Nov. lo,1963
1960
1962
14
16
20
24
26
28
32
34
36
38
Partum
20.0
17.8
17.3
15.5 50
15.5 48 5.2 75 190 1s
17.0 54 5.5
16.0 52
17.8 55 6.0 82
17.6 54 ._.
16.8
18.8 60 7.1
16.8 52
120 20
. . .
18.6 58 6.4 82 140 22
:: : 80
.
::: . .
a.b
.
.
73
5.6
86
Meyer,
876
Tulsky? Sigmann
and Silber
JO I.
45
110
[I Yen. cm.
on f
i-
Press.
I5
Saline
10 f-
Heart
Sound.
Sl L-.
time
1 rh P
20th
8eforcl
26th
32nd
3f3th
JAfta,
Pregnonry
FIG. 2. Case 1. Laboratory data before, during and following pregnancy. Note the tendency for dilution of blood in the initial 20 weeks which is reversed later in
pregnancy.
agents. The patient at the time of this report was scheduled for complete surgical correction of her lesion. CASE 2: This 21 year old white woman in her twenty-fifth week of pregnancy was known to have been a “blue baby” since her first year of life. At the age of 9 she was admitted to another hospital and found to be cyanotic at rest and dyspneic on moderate effort. The clinical, electrocardiographic and x-ray studies were reported to be consistent with tetralogy of Fallot. Right heart catheterization and angiocardiography confirmed this clinical impression. A
left-sided Potts’ operation was performed at this time. Cyanosis disappeared. At the age of 18 the patient maintained normal activity and was not cyanotic. X-ray films revealed moderate cardiomegaly with heavy vascular markings in the left lung field. The electrocardiogram showed evidence of left atria1 and left ventricular enlargement in addition to right ventricular hypertrophy. At the age of 21 the patient was followed-up She was digitalied and throughout her pregnancy. started on diuretic therapy prophylactically during the twenty-thiid week of pregnancy. Although no objective cause for her complaints of dyspnea, orthopTHE
AMERICAN
JOURNAL
OF
CARDIOLOQY
Pregnancy
and Tetralogy
877
of Fallot
vital capacity remained consistently in the range of predicted values. In the thirty-ninth week of gestation the patient was delivered uneventfully of a 5 lb. 12 oz. male child. The postpartum period was uncomplicated. Digitalization and diuretic therapy were stopped three months post partum. The patient has remained well except for recurrent bouts of paroxysmal atria1 tachycardia, for the control of which redigitalization and quinidine administration have been necessary.
DISCUSSION AVR
AVL
AVF
Vl
V2
V3
V4
Vs
V6
Case 2. Electrocardiogramrevealing left ventricular hypertrophy and strain with no associated features of right ventricular hypertrophy 11 years following an aortopulmonary shunt operation. There is a vertical position and digitalis alteration of the ST-T segment.
FIG. 3.
nea and palpitation was found, she was admitted to Michael Reese Hospital for further evaluation in her twenty-fifth week of gestation. On admission, the patient had no overt signs of heart failure; her lungs were clear; liver and spleen were not enlarged ; her neck veins were not engorged and only minimal ankle edema was present. The precordium was hyperactive with apical impulse palpable 2 cm. lateral to the midclavicular line as an accentuated and sustained heave. Blood pressure was 1601 50 mm. Hg, and the peripheral pulses were collapsing. An early ejection murmur closely followed the first sound ; the second sound was widely split with a small and late pulmonic component. A third sound was heard at the apex followed by a short diastolic flow murmur. In the pulmonic area a continuous machinery murmur was heard, and in the third intercostal space a loud, widely radiating systolic ejection murmur was present. The electrocardiogram revealed left ventricular hypertrophy and strain with no associated features of right ventricular hypertrophy (Fig. 3). Venous pressure was 143 mm. of saline and the circulation time (arm to tongue) was 14 sec. The patient was discharged, and the latter part of pregnancy was uneventful. Serial measurements of VOLUME14, DECEMBER1964
These 2 cases confirm the view that pregnancy is compatible with tetralogy of Fallot. Both patients were definitely proved by phonocardiography and by hemodynamic and other laboratory data to have tetralogy of Fallot. In only 20 of 46 patients previously reported was the diagnosis confirmed by such studies or by subsequent autopsy. Cyanosis, per se, does not represent a contraindication to pregnancy.5 Thus, among the 55 pregnancies previously reported, the over-all fetal mortality was 22, and maternal mortality, 7. There were 2 fetal losses and no maternal mortality in 9 of the patients who had shunt procedures prior to pregnancy. Both our patients carried their pregnancy without serious complication to both mother and child. The prognosis of mother and fetus has been related to the maternal hematocrit. In the presence of maternal bulboconal malformation, Neill’ found a fetal mortality of 85 per cent when the hematocrit exceeded 65 per cent, and 60 per cent with less severe hematocrit elevations. The problem of appropriate hematocrit in these circumstances is made more complex by the observation that patients with congenital cyanotic heart disease with elevated hematocrits may have hypochromic cells, suffer from relative anemia and require iron therapy.8 Shunt procedures have not only improved the prognosis, but also have altered the pathophysiology and, hence, the course of tetralogy of Fallot during pregnancy. The fraction of cardiac output shunted in tetralogy of Fallot, with a given size of a ventricular septal defect, is determined by the difference between the effective resistance offered by the peripheral arteries and that of the fixed obstruction at the pulmonic valve. This fraction, in turn, determines the arterial oxygen saturation which, presumably, determines the amount of stimulation of the hemopoietic system to vary both the relative and absolute volume change in the red blood
878
Meyer,
‘Fulsky,
cells. The increased blood viscosity in patients with this disease is due to the crythrocytosis so engendered. 9,liJ The phy’siologtr~ alterations induced by fvrgnancy produce a fall in the systemic perilhera resistance in two way.9~“~‘“: 1. By increasing plasma volume (40 to 50y0) in excess of the increase in red cell volume (20 to 3Ooj,), a hemodilution and lower viscosity result. This increase in plasma volume appears in the twelfth week of gestation and gradually increases until the twenty-fourth week, after which the rise is accelerated to reach a peak about the thirty-third week.12-16 2. The placenta, by behaving hemodynamically as an arteriovenous fistula,’ leads to a shunt effect. During the last month of pregnancy this action of the placenta declines. A pregnant patient with tetralogy of Fallot should, like the normal patient, have a similar placental shunting during the course of pregnancy. The reduced peripheral resistance in turn would lead to a progressively greater fraction of blood being shunted from the right to the left side of the heart.2r6 Pregnancy and Blood Viscosity: We assume that plasma volume rose in our patients, as expected, throughout pregnancy. This initially aggravated the disease in our first case, as documented by a rise in venous pressure, a drop in the arterial oxygen saturation and a dilution effect with the hematocrit approaching normal levels. Her unexpected clinical improvement in the latter half of pregnancy was associated with a rise in hematocrit which represented an almost twofold increase in the relative viscosity of the Because of the lack of homogeneity of blood.g the blood and the size of the capillaries it traverses, the effect of viscosity on resistance to flow cannot be approximated by Poiseuille’s law alone.‘6 Resistance across the pulmonic obstruction depends on whether flow is laminar However, there is some experior turbulent.” mental evidence that resistance rises with relative increase in viscosity in the hind legs of Thus, the effects of increased viscosity dogs.ls in tetralogy of Fallot are complex and matheNevertheless, it is posmatically unsolvable. sible that increased viscosity raised the resistance in the peripheral vascular bed significantly more than in the region of the relatively short and wide pulmonary valve. The result, if this were true, would be to reduce right to left shunt and even to enhance pulmonary flow in the latter part of pregnancy. This hypothesis
Sigmatln
and Silber
to ‘Iccount for our clinical observations is supported b!, the reappearance of the pulmonary component of the second sound in the phonocardiogram after having been absent in a sound tracing during the eighteenth week of gestation (,Fig. l).lg Analogous animal experiments should test this hypothesis. Pregnanry Following Shunt Procedure for TetralOgY: Our second case exemplifies one possible result in a patient following a shunt procedure. The hemodynamic status is altered by the operation which simulates a large patent ductus arteriosus with a significant left to right shunt. Consequently, there is an augmented volume load on the left ventricle. The electrocardiogram shows a striking evolution from a pattern of right ventricular hypertrophy to that of left ventricular hypertrophy and strain. Long term follow-up after shunt procedures20-23 in nearly 2,000 patients with tetralogy of Fallot reveals that moderate enlargement of the cardiac silhouette is common and is to be considered a manifestation of augmented volume load. In one series,*O combined ventricular hypertrophy was observed in two thirds of all patients 10 years after surgery. A more advanced evolution of the electrocardiogram, as seen in our second case, however, has not been mentioned. In one report,23 the possibility of left ventricular failure was mentioned but not documented. The relative resistance across the surgically induced defect will determine the size and direction of the shunt. In tetralogy of Fallot, a connection is created between a normal arterial vascular bed and pulmonary circulation “protected” by the obstruction at the pulmonic outflow tract. The resistance of the surgically induced defect itself, added to a possible functional constriction of the pulmonary vessels, prevents a massive left to right shunt. However, when the surgical shunt becomes large and the inherent resistance, therefore, becomes low, left ventricular failure due to volume overload may result. A reversal of the surgical shunt seems unlikely. However, increased shunting from right to left may occur in the interventricular defect inasmuch as the resistance of the fixed obstruction at the pulmonary outflow tract exceeds, in these patients, the systemic peripheral resistance. The variability of the latter in pregnancy, labor and the immediate postpartum period, for instance, are marked. The dramatic consequences of systemic hypotension seen in our first patient following delivTHE
AMERICAN
JOURNAL
OF
CARDIOLOGY
Pregnancy
and Tetralogy
ery, have been documented in a case reported by Hamiltonz3 in which the right to left shunt presumably varied between 100 per cent and zero as the arterial oxygen saturations increased from 15 per cent when the blood pressure was 65/30 mm. Hg to 85 per cent with a blood pressureof 165/110. Analysis of other patients with tetralogy of Fallot during pregnancy, as made by us in these two cases, may lend further support to our interpretations. SUMMARY
Two patients in their first pregnancy and with tetralogy of Fallot, proved by cardiac catheterization and angiocardiography, are Both delivered successfully at term. presented. In the first patient, age 16, the red blood cell count, hematocrit, arterial oxygen saturation and phonocardiogram had been examined frequently. A striking clinical improvement in the latter half of the pregnancy accompanied a rise of the hematocrit from 48 to 60 per cent. The pulmonic component of the second heart sound disappeared in the second trimester but was again recorded in the third, when the red These blood cell concentration was again high. data are discussed with special consideration of the role played by increased blood viscosity in the last trimester. The second patient, now 21 years old, had an augmented left ventricular volume load due to a Potts’ operation 11 years earlier. The possible effects of this type of surgical intervention on patients with tetralogy of Fallot during pregnancy are discussed.
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19. ACKNOWLEDGMENTS We are indebted to Dr. Louis N. Katz for his advice in preparing this report.
20.
REFERENCES 1. BURWELL, C. S. and METCALPE, J. Heart Diseases in Pregnancy, pp. 26 and 207. Boston, 1937. Little, Brown and Co. 2. MENDELSON,C. L. Cardiac Diseases in Pregnancy, p. 156. Philadelphia, 1960. F. A. Davis Co. 3. EASTMAN,N. Editorial. Obst. Gynec. Survey, 12 : 487, 1957. 4. BAKER, J. L. et al. Closed pulmonary valvulotomy
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in the management of Fallot’s tetralogy complicated by pregnancy. J. Obst. & Gynaec. Brit. Comm., 70: 154, 1963. BARNES, A. C. and REID, D. E. Discussion in: CANNEL, D. E. and VERNON, C. P. Congenital heart disease and pregnancy. Am. J. Obst. & Gynec., 85: 744, 1963. HYLAND, J. W. Discussion in: COPELAND,W. E., WOOLEY, C. F., RYAN, J. M., RUNCO, V. and LEVIN, H. S. Pregnancy and congenital heart disease. Am. J. Obst. f_%? Gym-c., 86: 107, 1963. NEILL, C. A. and SWANSON,S. Outcome of pregnancy in congenital heart disease (Abstr.). Circulation, 24: 1003, 1963. RUDOLPH, A. M., NADAS, A. S. and BORGES,W. H. Hematologic adjustment to cyanotic congenital heart disease. Pediatrics, 11: 454, 1953. PIROFSKY, B. The determination of blood viscosity in man by a method based on Poiseuille’s law. J. Clin. Invest., 32: 292, 1953. NELSON, W., MAYERSON, H. S., CLARK, J. H. and LYONS, C. Blood volume in congenital heart disease. J. Clin. Invest., 28: 860, 1947. ADAMS, J. Q. Cardiovascular physiology in normal pregnancy. Am. J. Obst. & Gynec., 67: 741, 1954. COHEN, M. E. and THOMSON, K. J. Studies on the circulation in pregnancy. J.A.M.A., 112: 1556, 1939. BERLIN, N. I., GOETSCH,C., HYDE, G. M. and PAX+ SONS, R. J. The blood volume in pregnancy. Surg. Gynec. & Obst., 97: 173, 1953. KELLAR, R. J. Toxemias of Pregnancy. In: Ciba Foundation Symposium, p. 135. Philadelphia, 1950. Blakiston Co. DIECKMANN,W. J. and WECENER, C. R. Studies of the blood in pregnancy. Arch. Znt. Med., 53: 71, 188,353,1934. GREEN, H. D. Medical Physics, Vol. II, p. 238. Chicago, 1950. Year Book Publishers. WITTAKER, S. R. and WINTON, F. R. The viscosity of blood. J. Physiol., 78: 338, 1933. VOGELPOEL,L. and SCHIURE,V. Auscultatory and phonocardiographic assessment of Fallot’s tetralogy. Circulation, 22: 73, 1960. PAUL, M. H., MILLER, R. A. and POTTS, W. J. Long term results of aortic-pulmonary anastomosis for tetralogy of Fallot. Circulation, 23: 525, 1961. TAUSSIC, H. B. and BAUERSFELD,S. R. Follow-up studies on first 1,000 patients operated on for pulmonary stenosis or atresia. Ann. Znt. Med., 38: 1, 1953. CAMPBELL,M. Late results of operations for Fallot’s tetralogy. Brit. M. J., 2: 1175, 1958. NADAS, A. S. Pediatric Cardiology, p. 656. Philadelphia, 1963. W. B. Saunders Co. HAMILTON, W. F., WINSLOW, J. A. and HAMILTON, W. F., JR. Notes on a case of congenital heart disease with cyanotic episodes. J. Clin. Invest. 29: 20, 1950.