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Fetal cardiovascular hemodynamics in the presence of complete atrioventricular block
Fetal cardiovascular hemodynamics in the presence of complete atrioventricular block Jean-Claude Veille, MD: and Wesley Covitz, MDb Winston-Salem, North Carolina OBJECTIVE: Our purpose was to follow serially the hemodynamic adaptation to a congenital complete heart block in a human fetus. STUDY DESIGN: Longitudinal and serial M-mode and Doppler echocardiography over a 10-week span were performed on a fetus affected by complete heart block. Ventricular fractional shortening, size, and flow across the atrioventricular valves and outflow tracts were determined starting at 20 weeks up to the time of delivery. Neonatal Doppler follow-up was performed at 2 days of life after implantation of a temporary pacemaker. RESULTS: The right and left ventricles were able to adapt to sustained bradycardia by increasing their size. This ventricular dilatation was also asspciated with an increase in fractional shortening, which was associated with ventricular free wall hypertrophy. When ventricular heart rate decreased to 38 beats/min, fractional shortening decreased, this was associated with the rapid onset of ascites and pericardial effusion. CONCLUSION: In the presence of sustained bradycardia ventricular output can increase, because this fetus was able to increase ventricular size and fractional shortening and wall thickness. (AM J OBSTET GVNECOl1994;170:1258-62.)
Key words: Congenital heart block, ventricular size and output Studies on fetal ventricular function have suggested that the fetal heart normally operates near or at the peak of the curve relating atrial pressure and ventricular stroke volume. '-3 Thus, to maintain cardiac output, the fetus has to manipulate its heart rate because it cannot readily change its stroke volume. This has led to the conclusion that the fetal heart is different from the adult heart in its ability to manipulate stroke volume in response to changes in heart rate,4. 5 although this has been questioned by others. 6 • 7 Data regarding such relationships are lacking in the human fetus, because the cardiovascular responses of the human fetus to normal and abnormal in utero conditions have been difficult to study. Reed et al." have reported on fetal cardiac function during tachyarrhythmias. 8 Lingman et al. 9 reported on one patient with complete heart block, but this observation was made late in the third trimester. With the recent introduction ofM-mode and pulsed Doppler echocardiography longitudinal studies of car-
From the Departments of Obstetrics and Gynecology" and Pediatrics, b Bowman Gray School of Medicme of Wake Forest University. Supported by National Insntutes of Health grant No. HL38296 from the Heart, Lung and Blood Institute (f.e. v,). Recezved for publzcation May 3, 1993; revised September 10, 1993; accepted November 30, 1993. Reprznt requests: Jean-Claude Veille, MD, Department of Obstetrics and Gynecology, Bowman Gray School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157. Copyright © 1994 by Mosby-Year Book, Inc. 0002-9378194 $3.00 + 0 6/1/53269
1258
diac function of the human fetus have been emerging.'o Ventricular size and function can be determined using M-mode and ventricular output can be estimated with pulsed Doppler flow across the atrioventricular valves and the great vessels so long as the area of the structure can be estimated. ,. The purpose of this study is to present the longitudinal interaction between heart rate, ventricular size, volume, and function in a human fetus affected by a third-degree heart block (complete heart block) whose mother had nuclear (SS-A) and cytoplasmic (Ro) antibodies, specific markers for Sjogren's syndrome. These immunoglobulin G antibodies cross the placenta and can cause complete heart block.' 2 Such congenital heart blocks have been reported to occur in one in 20,000 live born infants with structurally normal hearts. '3, . ,
Case report Our patient was a 35-year-old woman known to have Sjogren's syndrome and Hashimoto's thyroiditis. These diagnoses were confirmed 5 years ago during an acute episode of suppurative parotitis that was complicated by sepsis. She had been asymptomatic since that episode. She was first seen at 7 weeks of gestation for prenatal care. She was asymptomatic at that time, and the only medication she was receiving was levothyroxine sodium (Synthroid, Boots Pharma, Puerto Rico) 0.2 mg daily. Physical examination was essentially normal. Laboratory results were significant for the following: antinuclear antibody 1: 200, anticardiolipid antibody
Veille and Covitz
Volume 170. Number 5, Part 1 Am J Obstet Gynecol
1: 100, anti-double-stranded deoxyribonucleic acid negative; anti-SSNRo positive at > 1 : 64, anti-SSB/La negative, antibodies to smooth muscle positive, compatible with collagen vascular disease. The positive SSNRo confirmed Sjogren's syndrome. Pelvic ultrasonography confirmed an intrauterine pregnancy of 7 weeks. At 17 and 20 weeks repeat ultrasonography showed normal fetal growth, anatomy, and normal four-chamber fetal heart with a rate ranging between 142 and 153 beats/min. At each ultrasonographic examination, the estimation of the fetal weight was made with measurements of biparietal diameter and abdominal circumference. 15 The first M-mode and Doppler echocardiograms were made at the 20-week visit. At 22 weeks the fetal heart rate (FHR) was noted to be around 60 beats/min. Although steroid treatment of the mother for the possible suppression of the maternal antibodies was considered after consultation with the pediatric cardiologist, it was felt that such treatment will not result in an improvement in the complete heart block. Fetal M-mode and Doppler echocardiography documented the presence of a third-degree heart block (complete heart block). High-resolution ultrasonography was repeated every 2 weeks to monitor fetal ascites or pericardial effusion and twice a week when the ventricular heart rate fell below 60 beats/min. M-mode and Doppler echocardiograms were repeated every 2 to 3 weeks to analyze ventricular function and ventricular output. At 28 weeks ventricular heart rate dropped to 48 beats/min. Treatment with f3-mimetics or isoproterenol was considered to increase ventricular heart rate. It was felt that f3-mimetics would not improve the ventricular rate and that isoproterenol may be associated with significant side effects. Because of adequate fetal movement and growth we elected to observe and monitor closely. The thyroid function of the patient was rechecked and found to be adequate. She continued on her original thyroid treatment. The atrial heart rate was close to 110 to 112 beats/min. An M-mode study could not be obtained at this gestational age because of fetal position, but Doppler data are reported. A small, unilateral pericardial effusion was noted but was not large enough to be considered abnormal. A small degree of ascites was first documented at 30 weeks. Fetal growth, fetal movements, and assessment of fetal well-being were found to be satisfactory. At 31 weeks the patient noted decreased fetal movements, and repeat ultrasonography showed mild to moderate ascites. The pericardial effusion did not increase significantly from previous scans. Ventricular and atrial heart rates were 42 and 102 beats/min, respectively. The patient was admitted to the hospital for steroid administration to enhance fetal lung maturation. The next day repeat ultrasonography showed marked ascites. The ventricular heart rate had decreased to 38 beats/min (Fig. 1), and the atrial rate was 102 beats/min. The modified biophysical profile score was 2/8 (absent fetal movement, fetal tone, and fetal breathing). The decision was made to proceed to delivery by low-trans-
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Fig. 1. Superimposed are FHR and ventricular dimensions before and after onset of congenital heart block. Postdelivery data are also illustrated. Open circles, Values obtained for right ventricle at corresponding gestational age for normal fetuses.
verse cesarean section. A male infant with Apgar scores of 7 and 7 at 1 and 5 minutes, respectively, weighing 2105 gm was delivered. The umbilical venous pH was 7.35. The newborn had a ventricular heart rate of 38 beats/min, ascites, and hepatosplenomegaly. The infant was stabilized, and an isoproterenol drip was started to increase ventricular heart rate. The infant underwent echocardiography and placement of a temporary transvenous pacemaker. At 1 week of age a permanent epicardial pacemaker was implanted. Two months after deliv~ry the infant was discharged home in stable condition. Follow-up M-mode and Doppler examinations were performed at 6 months of age. Material and methods
All M-mode and Doppler echocardiogram studies were recorded on tape and on a strip chart recorder at a preset speed of 50 mm/sec and 100 mm/sec, respectively. M-mode echoes were obtained with the longitudinal axis with the cursor placed perpendicular to the septum to include the atrioventricular valves. The left and right endocardial point at their largest diameter were used to measure end-diastolic dimension. The nadir of the endocardial point was used to measure the end-systolic dimension. 8 End-diastolic dimension and end-systolic dimensions were measured with an on-line computer (Digisonics, Houston, Texas). Fractional shortening (or the percent change in dimension) was calculated in the following manner: End-diastolic dimension - End-systolic dimension/end-diastolic dimension X 100. The left and right free ventricular wall thickness was assessed by M-mode echocardiography. Pulsed Doppler of the atrioventricular valves were obtained with the four-chamber view. The size of the pulmonary artery and descending aorta were measured
1260
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May 1994 Am J Obslet Gynecol
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Fig. 2. Ventricular contractility (i.e., fractional shortening) for left and right heart are illustrated. Decrease in right ventricular fractional shortening at thirty-first week of study paralleled appearance on ultrasonography of fetal ascites and pericardial effusion.
with the short axis and during systole with the Doppler sample as parallel to the vessel as possible. The mean temporal velocity integral (i.e., the area under the Doppler curve) was measured from the strip chart hard copy with an on-line hand-held digitizer pen (Digisonics). At least four to six cardiac cycles were digitized and averaged. The diameters of the right and left atrioventricular valves annulae and the diameters of the vessels were recorded during diastole and systole, respectively, by means of two-dimensional echocardiograms and freeze frame. To document systole and diastole, a playback cine-loop was used to allow frame-by-frame analysis of the cardiac cycle. Flows were estimated by multiplying the values of the integration of the estimated instantaneous velocities for each of the vascular structures studied by their cross-sectional area and by the FHR. Results
The first M-mode and Doppler echocardiogram was performed at 20 weeks of gestation when the FHR was 149 beats/min (estimated fetal weight 380 gm). During this initial study M-mode echocardiography showed a normal left and right ventricular size and function. Io At 22 weeks FHR had decreased to about 60 beats/min. M-mode showed a complete A-V dissociation compatible with a complete heart block. During this scan right and left ventricular dimensions had significantly increased from the previous study (Fig. 1) and persisted throughout the remainder of the pregnancy (estimated fetal weight 728 gm). Values previously obtained on normal fetuses are illustrated by open circles and are included for comparison. Ventricular fractional shortening of both ventricular chambers continued to increase at the twenty-fifth week of study (estimated fetal
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Fig. 3. Illustration of significant increase in peak flow velocity in pulmonary artery and descending aorta before and after occurrence of complete heart block. These increases persisted until twenty-ninth week of gestation but decreased during last study at 31 weeks.
weight 906 gm) (Fig. 2). At the twenty-seventh week, however, fractional shortening decreased (estimated fetal weight 1602 gm). During the last echocardiogram examination at 31 weeks right ventricular fractional shortening, however, had significantly decreased when the ascites appeared (estimated fetal weight 2130 gm) (Fig. 2). Fractional shortening of the left ventricle increased to 57%. At 48 hours after birth, with the correction of heart rate, left ventricular contractility returned to a normal value. The right and left ventricular blood flows were indexed to the estimated fetal weight, which was calculated with biparietal diameter and abdominal circumference. I5 Measurements of the left and right free walls were not different from those previously obtained on normal human fetuses by means of the same technique in the early studies. s However, at the twenty-ninth and thirty-first week there was a significant increase in wall thickness of both ventricles (5 mm vs 3.2 mm for the 95th percentile in normal fetuses at this gestational age)." Peak flow velocity in the pulmonary artery, which had initially decreased at the onset of the block, remained elevated until the thirtyfirst week, at which time we documented fetal ascites. The peak flow velocity of the descending aorta increased with the appearance of the cardiac block up until the appearance of ascites at 31 weeks (Fig. 3). With the delivery and the correction of heart rate the pulmonary artery peak flow velocity decreased to normal values, whereas that of the descending aorta was still below reported values in the infant (normal values in children are 70 to 110 cm/sec for the pulmonary artery and 120 to 180 em/sec for the aorta).16 With the ventricular heart rate down to 38 beats/min, however, right
Veille and Covitz
Volume 170. Number 5. Part 1 Am J Obstet Gynecol
and left ventricular index decreased (Fig. 4). This decrease paralleled the appearance of ascites and pericardial effusion. Atrial rates, which were also monitored during this longitudinal study, ranged between 110 and 112 beats/min throughout the pregnancy until the day before delivery. During this last study the atrial rate dropped to 102 beats/min. With the placement of the temporary pacemaker after birth left ventricular output increased and the ascites improved.
Comment This report is the first to document the long-term adaptation in a human fetus to a congenital heart block in an otherwise structurally normal heart. These results would indicate that during prolonged and sustained bradycardia this fetus is able to manipulate its stroke volume by increasing ventricular size and fractional shortening and wall thickness to maintain cardiac output, a phenomenon previously observed in the adult heart. During the early part of this adaptation the ventricular free walls were not increased in size, but a significant increase occurred between the twenty-ninth and the thirty-first week. The net result was an increase in ventricular filling and an increase in ventricular fractional shortening with a corresponding increase in ventricular output. This observation is a departure from previous data obtained in the ovine fetus 4 and newborn 17 lamb during acute experimentation. Rudolph and Heymann 4 showed a direct linear relationship between the percent change in heart rate and right and left ventricular output. They suggested that heart rate played a dominant role in the regulation of fetal cardiac output, because the ovine fetal heart was shown to have a limited ability to increase or manipulate its stroke volume. 5 Kirkpatrick et al.,6 on the other hand, concluded that the Frank-Starling mechanism is not only operational in the ovine fetus but that it was an effective mechanism used to control cardiac output. They found that slow heart rates were not associated with a corresponding fall in cardiac output and suggested that heart rate was not the primary determinant of ventricular output in the ovine fetus. Anderson et aP found that ventricular stroke volume and output could be modulated independently of heart rate. They found that when heart rate was controlled with atrial pacing, left ventricular end-diastolic dimensions, stroke volume, and output significantly increased during the administration of isoproterenol. They concluded that the fetal left ventricle can increase stroke volume in response to such stimulus and that this change was not dependent on heart rate. Experimental data on fetal lambs suggest that both the right and left ventricles operate at the zenith of the curve relating stroke volume and arterial pressure. 2 • 3 These observations lead to the concept that
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25 Gestational Age (weeks) Fig. 4. Illustration of blood volume of right and left ventricular outflow tracts. Aorta refers to flow of descending aorta. No value of pulmonary artery was obtained at 22 weeb. Outputs indexed to estimated fetal weights also decreased at 31 weeks before fetal ascites. No postnatal flows were determined, because fetal and neonatal circulations are different and thus do not represent outflow from same ventricles.
ventricles of fetuses or young newborns have reduced compliance compared with adult hearts.17 Our findings woulc;l indicate that even when ventricular rate is kept constant, internal ventricular dimensions can increase and maintain adequate ventricular output. By means of two-dimensional echocardiogram and pulsed Doppler, Silverman and Schmidt l " reported ventricular size. contractility, and output in three fetuses with large sacral teratomas. In all three fetuses internal ventricular dimensions increased. Ventricular output was either maintained or increased, and contractility was maintained. These observations of human fetuses during long-term heart block or increase in preload suggest that under certain circumstances the size of the ventricles can increase to maintain cardiac output. Although some authors have suggested that the human fetus can use the Frank-Starling mechanism to regulate right or left ventricular output, these observations were made on term fetuses. Furthermore, only the effects of increasing FHR on cardiac output were observed. 19 The hemodynamic data presented in this paper are limited by the fact that they were obtained on a single fetus. Not all fetuses affected by a congenital heart block may respond in a similar manner. These results nonetheless are provocative and would support the experimental findings by Kirkpatrick et aLB and Anderson et aP The mechanism by which this fetus was able to increase
1262 Veille and Covitz
ventricular size and volume is not clear. End-diastolic dimension could have increased as a result of connective tissue remodeling, serial fiber replication, or increases in "preload." Thus during a congenital heart block the fetus was able to manipulate its stroke volume by increasing ventricular size fractional shortening and wall thickness to maintain an adequate output. Further studies are, however, required to confirm the above findings. In the presence of chronic and sustained fetal bradycardia M-mode and Doppler echocardiography should be added to the armamentarium of fetal surveillance. Timing for the delivery may, in turn, be helped by such noninvasive methods. Although fractional shortening does not reflect cardiac contractility, we speculate that when right ventricular fractional shortening decreased right-sided pressures increased, which in turn could have been, at least in part, responsible for the appearance of the ascites. REFERENCES
1. Gilbert RD. Control oHetal cardiac output during changes in blood volume. Am J Physiol 1980;238:H80-6. 2. Thornburg KL, Morton MJ. Filling and arterial pressure as determinants of RV stroke volume in the sheep fetus. Am J Physiol 1983;244:H656-63. 3. Thornburg KL, Morton MJ. Filling and arterial pressures as determinants of left ventricular stroke volume in the fetal lambs. Am J Physiol 1986;251 :H961-8. 4. Rudolph AM, Heymann MA. Circulatory changes during growth in the fetal lamb. Circ Res 1970;26:289-99. 5. Rudolph AM, Heymann MA. Cardiac output in the fetal lamb: the effects of spontaneous and induced changes of heart rate on right and left ventricular output. AM J OBSTET GYNECOL 1976;124:183-92. 6. Kirkpatrick SE, Pitlick PT, Naliboff J, Friedman WF. Frank-Starling relationship as an important determinant
May 1994 Am] Obstet Gynecol
of fetal cardiac output. Am J Physiol 1976;231:495-500. 7. Anderson PAW, Fair EC, Killam AP, et al. The in utero left ventricle of the fetal sheep: the effects of isoprenaline. J Physiol 1990;430:441-52. 8. Reed KL, Sahn DJ, Marx GR, Anderson CF, Shenker L. Cardiac Doppler flow during fetal arrhythmias: physiologic consequences. Obstet Gynecol 1987;70: 1-6. 9. Lingman G, Dahlstrom JA, Eik-Ness SH, Marsal K, Ohlin P, Ohrlander S. Haemodynamic assessment of fetal heart arrhythmias. Br J Obstet Gynaecol 1984;91 :647 -52. 10. VeilleJC, SivakoffM, Nemeth M. Evaluation of the human fetal cardiac size and function. Am J Perinatol 1990;7: 54-9. 11. DeSmedt MCH, Visser GHA, Meijboom EJ. Fetal cardiac output estimated by Doppler echocardiography during mid and late gestation. Am J Cardiol 1987;60:338-42. 12. Litsey SE, Noonan JA, O'Connor WN, Cottrill CM, Mitchell B. Maternal connective tissue disease and congenital heart block. N EnglJ Med 1985;312:98-100. 13. Veille JC, Sunderland C, Bennett RM. Complete heart block in a fetus associated with maternal Sjogren's syndrome. AMJ OBSTET GYNECOL 1985;151:660-1. 14. Schmidt KG, Ulmer HE, Silverman NH, Kleinman CS, Copel JA. Perinatal outcome of fetal complete atrioventricular block: a multicenter experience. J Am Coli Cardiol 1991;91:1360-6. 15. Shepard MJ, Richards VA, Berkowitz RL, Warsof SL, Hobbins J C. An evaluation of two equations for predicting fetal weight by ultrasound. AM J OBSTET GYNECOL 1982; 142:47-54. 16. Nanda NC, ed. Appendices in Doppler echocardiography. New York: Igaku-Shoin, 1985:482. 17. Romero TE, Friedman WF. Limited left ventricular response to volume overload in the neonatal period: a comparative study with the adult animal. Pediatr Res 1979; 13:91 0-5. 18. Silverman NH, Schmidt KG. Ventricular volume overload in the human fetus: observation from fetal echocardiography. J Am Soc Echocardiogr 1990;3:20-9. 19. Kenny J, Plappert T, Doubilet P, Saltzman D, St. John Sutton M. Effects of heart rate on ventricular size, stroke volume, and output in the normal human fetus: a prospective Doppler echocardiographic study. Circulation 1987;76:52-8.
Key words: Congenital heart block, ventricular size and output Studies on fetal ventricular function have suggested that the fetal heart normally operates near or at the peak of the curve relating atrial pressure and ventricular stroke volume. '-3 Thus, to maintain cardiac output, the fetus has to manipulate its heart rate because it cannot readily change its stroke volume. This has led to the conclusion that the fetal heart is different from the adult heart in its ability to manipulate stroke volume in response to changes in heart rate,4. 5 although this has been questioned by others. 6 • 7 Data regarding such relationships are lacking in the human fetus, because the cardiovascular responses of the human fetus to normal and abnormal in utero conditions have been difficult to study. Reed et al." have reported on fetal cardiac function during tachyarrhythmias. 8 Lingman et al. 9 reported on one patient with complete heart block, but this observation was made late in the third trimester. With the recent introduction ofM-mode and pulsed Doppler echocardiography longitudinal studies of car-
From the Departments of Obstetrics and Gynecology" and Pediatrics, b Bowman Gray School of Medicme of Wake Forest University. Supported by National Insntutes of Health grant No. HL38296 from the Heart, Lung and Blood Institute (f.e. v,). Recezved for publzcation May 3, 1993; revised September 10, 1993; accepted November 30, 1993. Reprznt requests: Jean-Claude Veille, MD, Department of Obstetrics and Gynecology, Bowman Gray School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157. Copyright © 1994 by Mosby-Year Book, Inc. 0002-9378194 $3.00 + 0 6/1/53269
1258
diac function of the human fetus have been emerging.'o Ventricular size and function can be determined using M-mode and ventricular output can be estimated with pulsed Doppler flow across the atrioventricular valves and the great vessels so long as the area of the structure can be estimated. ,. The purpose of this study is to present the longitudinal interaction between heart rate, ventricular size, volume, and function in a human fetus affected by a third-degree heart block (complete heart block) whose mother had nuclear (SS-A) and cytoplasmic (Ro) antibodies, specific markers for Sjogren's syndrome. These immunoglobulin G antibodies cross the placenta and can cause complete heart block.' 2 Such congenital heart blocks have been reported to occur in one in 20,000 live born infants with structurally normal hearts. '3, . ,
Case report Our patient was a 35-year-old woman known to have Sjogren's syndrome and Hashimoto's thyroiditis. These diagnoses were confirmed 5 years ago during an acute episode of suppurative parotitis that was complicated by sepsis. She had been asymptomatic since that episode. She was first seen at 7 weeks of gestation for prenatal care. She was asymptomatic at that time, and the only medication she was receiving was levothyroxine sodium (Synthroid, Boots Pharma, Puerto Rico) 0.2 mg daily. Physical examination was essentially normal. Laboratory results were significant for the following: antinuclear antibody 1: 200, anticardiolipid antibody
Veille and Covitz
Volume 170. Number 5, Part 1 Am J Obstet Gynecol
1: 100, anti-double-stranded deoxyribonucleic acid negative; anti-SSNRo positive at > 1 : 64, anti-SSB/La negative, antibodies to smooth muscle positive, compatible with collagen vascular disease. The positive SSNRo confirmed Sjogren's syndrome. Pelvic ultrasonography confirmed an intrauterine pregnancy of 7 weeks. At 17 and 20 weeks repeat ultrasonography showed normal fetal growth, anatomy, and normal four-chamber fetal heart with a rate ranging between 142 and 153 beats/min. At each ultrasonographic examination, the estimation of the fetal weight was made with measurements of biparietal diameter and abdominal circumference. 15 The first M-mode and Doppler echocardiograms were made at the 20-week visit. At 22 weeks the fetal heart rate (FHR) was noted to be around 60 beats/min. Although steroid treatment of the mother for the possible suppression of the maternal antibodies was considered after consultation with the pediatric cardiologist, it was felt that such treatment will not result in an improvement in the complete heart block. Fetal M-mode and Doppler echocardiography documented the presence of a third-degree heart block (complete heart block). High-resolution ultrasonography was repeated every 2 weeks to monitor fetal ascites or pericardial effusion and twice a week when the ventricular heart rate fell below 60 beats/min. M-mode and Doppler echocardiograms were repeated every 2 to 3 weeks to analyze ventricular function and ventricular output. At 28 weeks ventricular heart rate dropped to 48 beats/min. Treatment with f3-mimetics or isoproterenol was considered to increase ventricular heart rate. It was felt that f3-mimetics would not improve the ventricular rate and that isoproterenol may be associated with significant side effects. Because of adequate fetal movement and growth we elected to observe and monitor closely. The thyroid function of the patient was rechecked and found to be adequate. She continued on her original thyroid treatment. The atrial heart rate was close to 110 to 112 beats/min. An M-mode study could not be obtained at this gestational age because of fetal position, but Doppler data are reported. A small, unilateral pericardial effusion was noted but was not large enough to be considered abnormal. A small degree of ascites was first documented at 30 weeks. Fetal growth, fetal movements, and assessment of fetal well-being were found to be satisfactory. At 31 weeks the patient noted decreased fetal movements, and repeat ultrasonography showed mild to moderate ascites. The pericardial effusion did not increase significantly from previous scans. Ventricular and atrial heart rates were 42 and 102 beats/min, respectively. The patient was admitted to the hospital for steroid administration to enhance fetal lung maturation. The next day repeat ultrasonography showed marked ascites. The ventricular heart rate had decreased to 38 beats/min (Fig. 1), and the atrial rate was 102 beats/min. The modified biophysical profile score was 2/8 (absent fetal movement, fetal tone, and fetal breathing). The decision was made to proceed to delivery by low-trans-
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Fig. 1. Superimposed are FHR and ventricular dimensions before and after onset of congenital heart block. Postdelivery data are also illustrated. Open circles, Values obtained for right ventricle at corresponding gestational age for normal fetuses.
verse cesarean section. A male infant with Apgar scores of 7 and 7 at 1 and 5 minutes, respectively, weighing 2105 gm was delivered. The umbilical venous pH was 7.35. The newborn had a ventricular heart rate of 38 beats/min, ascites, and hepatosplenomegaly. The infant was stabilized, and an isoproterenol drip was started to increase ventricular heart rate. The infant underwent echocardiography and placement of a temporary transvenous pacemaker. At 1 week of age a permanent epicardial pacemaker was implanted. Two months after deliv~ry the infant was discharged home in stable condition. Follow-up M-mode and Doppler examinations were performed at 6 months of age. Material and methods
All M-mode and Doppler echocardiogram studies were recorded on tape and on a strip chart recorder at a preset speed of 50 mm/sec and 100 mm/sec, respectively. M-mode echoes were obtained with the longitudinal axis with the cursor placed perpendicular to the septum to include the atrioventricular valves. The left and right endocardial point at their largest diameter were used to measure end-diastolic dimension. The nadir of the endocardial point was used to measure the end-systolic dimension. 8 End-diastolic dimension and end-systolic dimensions were measured with an on-line computer (Digisonics, Houston, Texas). Fractional shortening (or the percent change in dimension) was calculated in the following manner: End-diastolic dimension - End-systolic dimension/end-diastolic dimension X 100. The left and right free ventricular wall thickness was assessed by M-mode echocardiography. Pulsed Doppler of the atrioventricular valves were obtained with the four-chamber view. The size of the pulmonary artery and descending aorta were measured
1260
Veille and Covitz
May 1994 Am J Obslet Gynecol
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Fig. 2. Ventricular contractility (i.e., fractional shortening) for left and right heart are illustrated. Decrease in right ventricular fractional shortening at thirty-first week of study paralleled appearance on ultrasonography of fetal ascites and pericardial effusion.
with the short axis and during systole with the Doppler sample as parallel to the vessel as possible. The mean temporal velocity integral (i.e., the area under the Doppler curve) was measured from the strip chart hard copy with an on-line hand-held digitizer pen (Digisonics). At least four to six cardiac cycles were digitized and averaged. The diameters of the right and left atrioventricular valves annulae and the diameters of the vessels were recorded during diastole and systole, respectively, by means of two-dimensional echocardiograms and freeze frame. To document systole and diastole, a playback cine-loop was used to allow frame-by-frame analysis of the cardiac cycle. Flows were estimated by multiplying the values of the integration of the estimated instantaneous velocities for each of the vascular structures studied by their cross-sectional area and by the FHR. Results
The first M-mode and Doppler echocardiogram was performed at 20 weeks of gestation when the FHR was 149 beats/min (estimated fetal weight 380 gm). During this initial study M-mode echocardiography showed a normal left and right ventricular size and function. Io At 22 weeks FHR had decreased to about 60 beats/min. M-mode showed a complete A-V dissociation compatible with a complete heart block. During this scan right and left ventricular dimensions had significantly increased from the previous study (Fig. 1) and persisted throughout the remainder of the pregnancy (estimated fetal weight 728 gm). Values previously obtained on normal fetuses are illustrated by open circles and are included for comparison. Ventricular fractional shortening of both ventricular chambers continued to increase at the twenty-fifth week of study (estimated fetal
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Fig. 3. Illustration of significant increase in peak flow velocity in pulmonary artery and descending aorta before and after occurrence of complete heart block. These increases persisted until twenty-ninth week of gestation but decreased during last study at 31 weeks.
weight 906 gm) (Fig. 2). At the twenty-seventh week, however, fractional shortening decreased (estimated fetal weight 1602 gm). During the last echocardiogram examination at 31 weeks right ventricular fractional shortening, however, had significantly decreased when the ascites appeared (estimated fetal weight 2130 gm) (Fig. 2). Fractional shortening of the left ventricle increased to 57%. At 48 hours after birth, with the correction of heart rate, left ventricular contractility returned to a normal value. The right and left ventricular blood flows were indexed to the estimated fetal weight, which was calculated with biparietal diameter and abdominal circumference. I5 Measurements of the left and right free walls were not different from those previously obtained on normal human fetuses by means of the same technique in the early studies. s However, at the twenty-ninth and thirty-first week there was a significant increase in wall thickness of both ventricles (5 mm vs 3.2 mm for the 95th percentile in normal fetuses at this gestational age)." Peak flow velocity in the pulmonary artery, which had initially decreased at the onset of the block, remained elevated until the thirtyfirst week, at which time we documented fetal ascites. The peak flow velocity of the descending aorta increased with the appearance of the cardiac block up until the appearance of ascites at 31 weeks (Fig. 3). With the delivery and the correction of heart rate the pulmonary artery peak flow velocity decreased to normal values, whereas that of the descending aorta was still below reported values in the infant (normal values in children are 70 to 110 cm/sec for the pulmonary artery and 120 to 180 em/sec for the aorta).16 With the ventricular heart rate down to 38 beats/min, however, right
Veille and Covitz
Volume 170. Number 5. Part 1 Am J Obstet Gynecol
and left ventricular index decreased (Fig. 4). This decrease paralleled the appearance of ascites and pericardial effusion. Atrial rates, which were also monitored during this longitudinal study, ranged between 110 and 112 beats/min throughout the pregnancy until the day before delivery. During this last study the atrial rate dropped to 102 beats/min. With the placement of the temporary pacemaker after birth left ventricular output increased and the ascites improved.
Comment This report is the first to document the long-term adaptation in a human fetus to a congenital heart block in an otherwise structurally normal heart. These results would indicate that during prolonged and sustained bradycardia this fetus is able to manipulate its stroke volume by increasing ventricular size and fractional shortening and wall thickness to maintain cardiac output, a phenomenon previously observed in the adult heart. During the early part of this adaptation the ventricular free walls were not increased in size, but a significant increase occurred between the twenty-ninth and the thirty-first week. The net result was an increase in ventricular filling and an increase in ventricular fractional shortening with a corresponding increase in ventricular output. This observation is a departure from previous data obtained in the ovine fetus 4 and newborn 17 lamb during acute experimentation. Rudolph and Heymann 4 showed a direct linear relationship between the percent change in heart rate and right and left ventricular output. They suggested that heart rate played a dominant role in the regulation of fetal cardiac output, because the ovine fetal heart was shown to have a limited ability to increase or manipulate its stroke volume. 5 Kirkpatrick et al.,6 on the other hand, concluded that the Frank-Starling mechanism is not only operational in the ovine fetus but that it was an effective mechanism used to control cardiac output. They found that slow heart rates were not associated with a corresponding fall in cardiac output and suggested that heart rate was not the primary determinant of ventricular output in the ovine fetus. Anderson et aP found that ventricular stroke volume and output could be modulated independently of heart rate. They found that when heart rate was controlled with atrial pacing, left ventricular end-diastolic dimensions, stroke volume, and output significantly increased during the administration of isoproterenol. They concluded that the fetal left ventricle can increase stroke volume in response to such stimulus and that this change was not dependent on heart rate. Experimental data on fetal lambs suggest that both the right and left ventricles operate at the zenith of the curve relating stroke volume and arterial pressure. 2 • 3 These observations lead to the concept that
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25 Gestational Age (weeks) Fig. 4. Illustration of blood volume of right and left ventricular outflow tracts. Aorta refers to flow of descending aorta. No value of pulmonary artery was obtained at 22 weeb. Outputs indexed to estimated fetal weights also decreased at 31 weeks before fetal ascites. No postnatal flows were determined, because fetal and neonatal circulations are different and thus do not represent outflow from same ventricles.
ventricles of fetuses or young newborns have reduced compliance compared with adult hearts.17 Our findings woulc;l indicate that even when ventricular rate is kept constant, internal ventricular dimensions can increase and maintain adequate ventricular output. By means of two-dimensional echocardiogram and pulsed Doppler, Silverman and Schmidt l " reported ventricular size. contractility, and output in three fetuses with large sacral teratomas. In all three fetuses internal ventricular dimensions increased. Ventricular output was either maintained or increased, and contractility was maintained. These observations of human fetuses during long-term heart block or increase in preload suggest that under certain circumstances the size of the ventricles can increase to maintain cardiac output. Although some authors have suggested that the human fetus can use the Frank-Starling mechanism to regulate right or left ventricular output, these observations were made on term fetuses. Furthermore, only the effects of increasing FHR on cardiac output were observed. 19 The hemodynamic data presented in this paper are limited by the fact that they were obtained on a single fetus. Not all fetuses affected by a congenital heart block may respond in a similar manner. These results nonetheless are provocative and would support the experimental findings by Kirkpatrick et aLB and Anderson et aP The mechanism by which this fetus was able to increase
1262 Veille and Covitz
ventricular size and volume is not clear. End-diastolic dimension could have increased as a result of connective tissue remodeling, serial fiber replication, or increases in "preload." Thus during a congenital heart block the fetus was able to manipulate its stroke volume by increasing ventricular size fractional shortening and wall thickness to maintain an adequate output. Further studies are, however, required to confirm the above findings. In the presence of chronic and sustained fetal bradycardia M-mode and Doppler echocardiography should be added to the armamentarium of fetal surveillance. Timing for the delivery may, in turn, be helped by such noninvasive methods. Although fractional shortening does not reflect cardiac contractility, we speculate that when right ventricular fractional shortening decreased right-sided pressures increased, which in turn could have been, at least in part, responsible for the appearance of the ascites. REFERENCES
1. Gilbert RD. Control oHetal cardiac output during changes in blood volume. Am J Physiol 1980;238:H80-6. 2. Thornburg KL, Morton MJ. Filling and arterial pressure as determinants of RV stroke volume in the sheep fetus. Am J Physiol 1983;244:H656-63. 3. Thornburg KL, Morton MJ. Filling and arterial pressures as determinants of left ventricular stroke volume in the fetal lambs. Am J Physiol 1986;251 :H961-8. 4. Rudolph AM, Heymann MA. Circulatory changes during growth in the fetal lamb. Circ Res 1970;26:289-99. 5. Rudolph AM, Heymann MA. Cardiac output in the fetal lamb: the effects of spontaneous and induced changes of heart rate on right and left ventricular output. AM J OBSTET GYNECOL 1976;124:183-92. 6. Kirkpatrick SE, Pitlick PT, Naliboff J, Friedman WF. Frank-Starling relationship as an important determinant
May 1994 Am] Obstet Gynecol
of fetal cardiac output. Am J Physiol 1976;231:495-500. 7. Anderson PAW, Fair EC, Killam AP, et al. The in utero left ventricle of the fetal sheep: the effects of isoprenaline. J Physiol 1990;430:441-52. 8. Reed KL, Sahn DJ, Marx GR, Anderson CF, Shenker L. Cardiac Doppler flow during fetal arrhythmias: physiologic consequences. Obstet Gynecol 1987;70: 1-6. 9. Lingman G, Dahlstrom JA, Eik-Ness SH, Marsal K, Ohlin P, Ohrlander S. Haemodynamic assessment of fetal heart arrhythmias. Br J Obstet Gynaecol 1984;91 :647 -52. 10. VeilleJC, SivakoffM, Nemeth M. Evaluation of the human fetal cardiac size and function. Am J Perinatol 1990;7: 54-9. 11. DeSmedt MCH, Visser GHA, Meijboom EJ. Fetal cardiac output estimated by Doppler echocardiography during mid and late gestation. Am J Cardiol 1987;60:338-42. 12. Litsey SE, Noonan JA, O'Connor WN, Cottrill CM, Mitchell B. Maternal connective tissue disease and congenital heart block. N EnglJ Med 1985;312:98-100. 13. Veille JC, Sunderland C, Bennett RM. Complete heart block in a fetus associated with maternal Sjogren's syndrome. AMJ OBSTET GYNECOL 1985;151:660-1. 14. Schmidt KG, Ulmer HE, Silverman NH, Kleinman CS, Copel JA. Perinatal outcome of fetal complete atrioventricular block: a multicenter experience. J Am Coli Cardiol 1991;91:1360-6. 15. Shepard MJ, Richards VA, Berkowitz RL, Warsof SL, Hobbins J C. An evaluation of two equations for predicting fetal weight by ultrasound. AM J OBSTET GYNECOL 1982; 142:47-54. 16. Nanda NC, ed. Appendices in Doppler echocardiography. New York: Igaku-Shoin, 1985:482. 17. Romero TE, Friedman WF. Limited left ventricular response to volume overload in the neonatal period: a comparative study with the adult animal. Pediatr Res 1979; 13:91 0-5. 18. Silverman NH, Schmidt KG. Ventricular volume overload in the human fetus: observation from fetal echocardiography. J Am Soc Echocardiogr 1990;3:20-9. 19. Kenny J, Plappert T, Doubilet P, Saltzman D, St. John Sutton M. Effects of heart rate on ventricular size, stroke volume, and output in the normal human fetus: a prospective Doppler echocardiographic study. Circulation 1987;76:52-8.