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Left ventricular systolic and diastolic function in pregnant patients with sickle cell disease
Left ventricular systolic and diastolic function in pregnant disease patients with sickle cell Jean-Claude
Veille,
MD, and Regina
Hanson,
RDMS
Winston-Salem, North Carolina
OBJECTIVE: Our purpose was to document noninvasively the effect of sickle cell disease on left ventricular systolic and diastolic function during the third trimester of pregnancy. STUDY DESIGN: Fifteen patients with sickle cell disease underwent a two-dimensional M-mode echocardiography obtained using the long axis with the cursor placed at the level of the tip of the mitral valve. All studies were performed with the patient in the left lateral decubitus. A group of 40 normal pregnant patients served as controls. None of the patients had evidence of cardiovascular disease. Left atrial and ventricular dimensions and mass were calculated and averaged. Left ventricular systolic and diastolic function were assessed. RESULTS: Pregnant patients with sickle cell disease had a significant enlargement of the left ventricular end-diastolic dimension, posterior wall, Interventricular septum, and ventricular mass than the control group. Although heart rate and fractional shortening were not different between the two groups, stroke volume and cardiac output were higher in patients with sickle cell disease. This was mostly because of enlargement of left end-diastolic dimension. Ventricular diastolic function was different in patients with sickle cell disease, resulting in an increase in the duration of the rapid filling. CONCLUSION: Left ventricular systolic function in patients with sickle cell disease was not affected in spite of a marked ventricular hypertrophy and ventricular enlargement. Diastolic function, however, was lower in the sickle cell group, which indicates a decrease in ventricular compliance. These patients had a higher cardiac output than did a normal pregnant group in the third trimester. This was accomplished by increasing ventricular size without increasing heart rate or fractional shortening. (AM J Oestet GmEcoi. 1994; 170: 107-10. )
Key words: Left ventricular function, sickle cell, pregnancy Although maternal mortality in patients with sickle disease has been reported as high as 10% to 14% during pregnancy, '. 2 improved management of these has decreased a patients maternal mortality to about 1%.5" ; Patients with sickle cell disease have cardiac dysfunction, '. 6 and pregnancy may affect left ventricular systolic and diastolic function, resulting in cardiovascular insufficiency. " To date, there is no information regarding the effect of pregnancy on left ventricular diastolic function in this patient population and systolic during the third trimester. The aim of this study was to test the hypothesis that pregnancy significantly affects left ventricular systolic and diastolic function in patients diseases. M-mode cell sickle with echocardiography was From the Department of Obstetricsand Gynecology,Bowman Gray School of Medicine of Wake Forest University. Supported in part by National Institutes of Health, Natumal Heart, Lung, and Blood Institute grant No. HL38296 (/. C. V.).
Received for publication May 10,1993. August accepted
17,1993;
revised July
30,1993;
Reprint requests:Jean-Claude Vedle, MD, Department of Obstetrics Bowman Gray School GynecologX of Medicine, Winston-Salem, and NC 27157. Copyright © 1994 by Mosby-Year Book, Inc. 0002-9378/94 $1.00 + .20 6/1/50628
used to document left ventricular size and function during systole and diastole. A group of normal patients were used for comparison during the third trimester of gestation. Method Two-dimensional M-mode echocardiograms with a 3.5 MHz phased-array transducer were obtained in 10 black pregnant patients with homozygous sickle cell anemia and five women with sickle cell-hemoglobin C disease. A group of 40 normal pregnant patients with no complications was also evaluated during the third trimester. All of the patients were normotensive and had no cardiovascular disease. The only medication taken by the subjects were prenatal vitamins. Informed consents previously approved by the Institutional Review Committee of the hospital were obtained before the study. M-mode echocardiograms were obtained using an ATL UN19 (Advanced Technology, Bothell, `Nash.). All patients were studied in the left lateral decubitus position after a 15-minute rest. M-mode echocardiography has previously been described and has been found to be a reliable and acceptable noninvasive method to assesscardiac function during preg-
107
108
Veille and Hanson
January 1994 Am J Obstet Gynecol
Table I. Results (means ± SEM) I
Variable
Control
Heart rate (beats/min) Mean arterial pressure (mm Hg) End-diastolic dimension (mm) Left atrium (mm) Left ventricle posterior wall thickness diastole (mm) Interventricular septum diastole (mm) Mass (gm) Fractional shortening (%) Stroke volume (ml) Cardiac output (Umin) Total peripheral resistance (dynes " sec " cm Hemoglobin (%)
86.6 69.5 49.4 35.2 7.1
± ± ± ± ±
1.8 0.9 0.7 1.1 0.2
8.4 141.9 37.9 72.3 6.395 939.6 11.9
± ± ± ± ± ± ±
0.3 9.0 0.9 3.1 0.28 49.3 0.1
Sickle cell 78.5 67.7 52.7 38.3 11.7 11.7 303.7 38.7 91.3 7.596 780.8 8.7
± ± ± ± ±
6.3 1.8 1.5 1.6 0.5
± 0.4 20.9 ± 1.8 ± 6.7 ± 0.54 ± 80.9 ± 0.2
Significance NS NS p<0.03 NS p<0.00001 p<0.00001 p<0.00001 NS p<0.05 p<0.03 NS p<0.0001
NS, Not significant.
nancy. ' Briefly, the transducer was placed in the left third or fourth intercostal space to obtain a long axis The M-mode view of the left ventricle. cursor was positioned at the level of the chordae tendinea and moved toward the annulus to obtain views of the left cavity with a flick of the mitral valve. " A ventricular sweep of the left ventricle was then obtained, and to the left atrium were recorded on a strip chart at a speed of 50 mm/sec. Left dimensions obtained from the ventricular end-diastolic onset of QRS complex and the end-systolic dimensions returning
echoes perpendicular
at the end-diastolic nadir of the septal motion, according to recommendations made by Sahn et al., ' Six consecutive were analyzed. cardiac cycles were obtained
measured
and
averaged. The following (1) left ventricular volume
calculations
were obtained: or end-systolic volume = 7D/2.4 + D, where D= end-diastolic dimension (2) stroke volor end-systolic dimensions, ume = end-diastolic volume - end-systolic volume, (3) in dimen(percent change dimensions - end-systolic disions) = end-diastolic dimensions = 100, (4) cardiac mensions/end-diastolic output = stroke volume x heart rate. Left ventricular diastolic function was determined by tracing the septum fractional
shortening
wall from the M-mode hard copy with a digital light pen and graphic overlay. computer-assisted and posterior
Peak filling rate of the left ventricle during diastole, the duration of rapid filling, and the peak rate of systolic thickening and peak rate of diastolic thinning were determined by the interventricular septum and left posterior wall. Total peripheral resistance was obtained as follows: Total peripheral resistance = 80 (Mean blood pressure/Cardiac output), where Mean ventricular
arterial pressure = Systolic +2 Diastolic/3. Statistical between Comparison analysis.
the
two
t test with a groups were made with the unpaired level of 0.05 to reject the null two-sided significance hypothesis. Results are presented as means and SEM.
Results Mean gestational age at the time of this study was not different between the controls and the patients with sickle cell disease (35 ±1 vs 34 -1 weeks, p= not significant). None of the patients had preeclampsia or any hypertensive disorders. Left ventricular M-mode echocardiogram results are shown in Table I. Left ventricular end-diastolic dimension was larger in the sickle cell group, but there was no difference in the left atrial dimensions. Left ventricular wall interventricular septal size during diastole and cardiac mass were significantly greater in patients with sickle cell disease compared with the control group (Table I). Although heart rate and fractional shortening were not different between the two groups, stroke volume and cardiac output were significantly greater in the patients with sickle cell disease. The hemoglobin was significantly lower in the sickle cell patients (8.5% ± 0.2% vs 11.9% ± 0.1%, p<0.0001). Left ventricle diastolic function results are shown in Table II. The peak filling rate of the left ventricle during diastole was significantly lower in the sickle cell group when compared with the normal group (Table II). The duration of rapid filling of the left ventricle was significantly longer in patients with sickle cell disease (Table II). Septal rate of systolic thickening and the rate of septal diastolic thinning was not different between the two groups. Left ventricular posterior wall diastolic thinning was significantly shorter in the patients with sickle cell disease (Table II). No abnormality of the normalized peak rate of systolic thickening was found during the analysis of either septal or left posterior wall motion. There was no difference in the total peripheral resistance between the normal and the patients affected by sickle cell disease (938.6 ± 49.3 vs 780.8 ± 80.9 dynes - sec - cm-'). There was no significant difference in either measured or derived cardiovascular parameters between the patients affected by SS or SC disease.
Veille and Hanson
Volume 170, Number 1, Part I Am J Obstet Gynecol
109
Table II. Diastolic values (mean ± SEM) Control Left ventricle Left ventricular diastolic relaxation-diastole (cm/sec) Duration of rapid filling (msec) Septum Normalized peak rate of systolic thickening second Normalized peak rate of diastolic thinning second Posterior wall Normalized peak rate of systolic thickening second Normalized peak rate of diastolic thinning second
per per
per per
Sickle cell
Significance
14.6 ± 0.9
11.5 t 0.5
p<0.03
165.8 ± 7.8
205.7 ± 12.3
p<0.009
2.8 ± 0.1
2.4 ± 0.2
NS
2.8 ± 0.1
2.3 ± 0.3
NS
5.3 ± 0.4
4.4 ± 0.5
NS
8.5 ± 0.9
5.1 ± 0.7
p<0.02
NS, Not significant.
Comment During the third trimester of pregnancy left ventricular end-diastolic dimension was significantly greater in disease than by a normal pregcell with sickle patients left The group. ventricles of patients with control nant thicker, which in sickle cell disease were significantly diastolic relaxation. The turn affected left ventricular disease left in the atrium patients sickle cell with of size larger than that of the control was not significantly difference in hemoIn the spite of a significant group. globin level between the two groups, heart rate and between the fractional shortening were not different larger stroke volume and groups. The significantly found in the patients with sickle cell output cardiac disease is secondary to the increase in end-diastolic dimension and is not because of increases in heart rate '° This reflects an adequate fractional shortening. or adjustment to chronic anemia. The peak both thickening the interventricular of systolic rate of left posterior wall was not different in the and septum for dimension. both groups, even when normalized
hemodynamic
The diastolic relaxation of the left ventricle was sigin disease, decreased the group with sickle cell nificantly longer for filling in time the rapid a of resulted which diastolic Although septal relaxation and that chamber. by this state of affected not were thickening systolic diastolic thinning of the posterior the anemia, chronic disease. in lower the with sickle cell patients wall was This abnormal diastolic relaxation can be secondary to decreased ventricular compliance or impaired left venischemia, Preload, myocardial tricular contractile state. or even atrial contraction abnormality may all play a diastolic in the observed ventricular significant role filling. The abnormal diastolic function found in these by left likely is ventriccaused most pregnant patients left in increase by hypertrophy the ventricular and ular
mass. The most likely explanation for this hypertrophy is local ischemic changes secondary to either chronic anemia, sickling, or obstruction of the microcirculation, rather than in a response to an increase in systemic vascular resistance. Thus, in pregnant patients with sickle cell disease, systolic function was found to be normal, but diastolic ventricular relaxation was found to be impaired. This study demonstrates that the increased cardiac output requirements that occur during pregnancy are met by a greater increase in left ventricular end-diastolic dimension. Although we demonstrated diastolic relaxation differences of the left ventricle in these patients at rest, these changes do not seem to affect left ventricular systolic function and output. In children with sickle cell disease left ventricular mass was found to increase when enlargement of the left ventricle could defor the not adequately compensate myocardium mands. " In adults with sickle cell disease the normalized rate of change of the left ventricular cavity dimension in diastole was significantly lower when compared with a group of normal controls. Left posterior wall relaxation when normalized for dimension was also " Although lower in the cell group. sickle significantly we found similar findings in a pregnant population with left in decrease disease, ventricle complithe sickle cell ance did not result in an abnormal volume-length has been assoleft which the ventricle, relationship of " dysfunction. It is always possible ciated with cardiac that such diastolic dysfunction could eventually result in systolic dysfunction and abnormal ejection fraction or wall motion abnormality during periods of cardiac stress or exercise, as has been reported. ' Our study demonstrates that these patients adapt well to pregnancy and that accessory mechanisms such as heart rate or fractional shortening used normally to maintain or to
110 Veille and Hanson
increase cardiac output during acute anemia are not required under normal conditions in the third trimester in these patients with chronic anemia. Covitz et al. 'Y found that the septum was hypertrophied in patients with sickle cell disease. Such abnormality in the septal relaxation may be related to biventricular wall stress and may in turn affect diastolic filling and normal ventricular emptying or filling. " In the current study we also found significant septal hypertrophy, which could have affected ventricular filling without affecting ventricular systolic function and cardiac output. Thus these patients have slowed relaxation and decreased diastolic distensibility, which eventually can result in an elevation of filling pressures and in an inability of the ventricle to fill during diastole. These abnormalities in diastolic filling may in turn influence systolic pump function and may cause pulmonary congestion during such stress periods as exercise and episodes of tachycardia. The presence of diastolic abnormality in these pregnant patients, however, should alert the obstetrician to the possibility that labor or the postpartum period may put these patients at a greater risk for cardiovascular stress. This study supports our original hypothesis that sickle cell disease significantly affects the systolic and diastolic function of the left ventricle during pregnancy. In spite of some diastolic dysfunction these patients can adequately adjust to the cardiovascular stress of pregnancy, and they appear to have no impairment of the left ventricular systolic function. To properly document the effect of pregnancy on cardiac function in patients with sickle cell disease, a study should be conducted to compare the same patients in a nonpregnant state. We thank Dr. W. Covitz for reviewing and analyzing our data.
January 1994 Am J Obstet Gynecol
REFERENCES 1. Fort AT, Morrison JC, Berreras L, Diggs LW, Fish SA. Counselling the patient with sickle cell disease about reproduction: pregnancy outcome does not justify the maternal risk. A.M J Ousrsr GYNECOL1971; 111: 324-7. 2. Hendricks JP, de V Harrison KA, Watson-Williams EJ, Luzzatto L, Ajabor LN. Pregnancy in homozygous sickle cell anemia. J Obstet Gynecol Br Commonw 1979; 79: 396409. 3. Milner PF, Jones BR, Döbler J. Outcome of pregnancy in sickle cell anemia and sickle cell hemoglobin C disease. A.H J Oesrer GYNECOL1980; 138:239-45. 4. Powars DR, Sandhu M, Niland-Weiss J, Johnson C, Bruce S, Manning PR. Pregnancy in sickle cell disease. Obstet Gynecol 1986; 67: 217-28. 5. Gerry JL, Bulkley BH, Hutchins GM. Clinicopathologic analysis of cardiac dysfunction in 52 patients with sickle cell anemia. Am J Cardiol 1978;42: 211-6. 6. Balfour IC, Covitz W, Arensman FW, Eubig C, Garrido M, Jones C. Left ventricular filling in sickle cell anemia. Am J Cardiol 1988; 61: 395-9. 7. Veille JC, Morton MJ, Paul MS. Maternal left ventricular dimension in pregnancies complicated by fetal growth retardation. Obstet Gynecol 1991; 78: 265-9. 8. Popp RI, Filly K, Brown OR, Harrison DC. Effect of transducer placement on echocardiographic measurements of left ventricular dimensions. Am J Cardiol 1975; 35: 537-40. 9. Sahn DJ, DeMaria A. Kisslo J, et al. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978; 58: 1072-7. 10. Gibson DG, Traill TA, Hall RJC, Brown DJ. Echocardiographic features of secondary left ventricular hypertrophy. Br Heart J 1979; 41: 54-9. 11. Balfour IC, Covitz W, Davis H, Syamasundar R, Strong WB, Alpert BS. Cardiac size and function in children with sickle cell anemia. Am Heart J 1984; 108:345-50. 12. Covitz W, Eubig C, Balfour IC, et al. Exercise-induced cardiac dysfunction in sickle cell anemia: a radionuclide study. Am J Cardiol 1983; 51: 570-5. 13. Grossman W, MeLaurin L. Diastolic properties of the left ventricle. Ann Intern Med 1976;84: 316-26.
Veille,
MD, and Regina
Hanson,
RDMS
Winston-Salem, North Carolina
OBJECTIVE: Our purpose was to document noninvasively the effect of sickle cell disease on left ventricular systolic and diastolic function during the third trimester of pregnancy. STUDY DESIGN: Fifteen patients with sickle cell disease underwent a two-dimensional M-mode echocardiography obtained using the long axis with the cursor placed at the level of the tip of the mitral valve. All studies were performed with the patient in the left lateral decubitus. A group of 40 normal pregnant patients served as controls. None of the patients had evidence of cardiovascular disease. Left atrial and ventricular dimensions and mass were calculated and averaged. Left ventricular systolic and diastolic function were assessed. RESULTS: Pregnant patients with sickle cell disease had a significant enlargement of the left ventricular end-diastolic dimension, posterior wall, Interventricular septum, and ventricular mass than the control group. Although heart rate and fractional shortening were not different between the two groups, stroke volume and cardiac output were higher in patients with sickle cell disease. This was mostly because of enlargement of left end-diastolic dimension. Ventricular diastolic function was different in patients with sickle cell disease, resulting in an increase in the duration of the rapid filling. CONCLUSION: Left ventricular systolic function in patients with sickle cell disease was not affected in spite of a marked ventricular hypertrophy and ventricular enlargement. Diastolic function, however, was lower in the sickle cell group, which indicates a decrease in ventricular compliance. These patients had a higher cardiac output than did a normal pregnant group in the third trimester. This was accomplished by increasing ventricular size without increasing heart rate or fractional shortening. (AM J Oestet GmEcoi. 1994; 170: 107-10. )
Key words: Left ventricular function, sickle cell, pregnancy Although maternal mortality in patients with sickle disease has been reported as high as 10% to 14% during pregnancy, '. 2 improved management of these has decreased a patients maternal mortality to about 1%.5" ; Patients with sickle cell disease have cardiac dysfunction, '. 6 and pregnancy may affect left ventricular systolic and diastolic function, resulting in cardiovascular insufficiency. " To date, there is no information regarding the effect of pregnancy on left ventricular diastolic function in this patient population and systolic during the third trimester. The aim of this study was to test the hypothesis that pregnancy significantly affects left ventricular systolic and diastolic function in patients diseases. M-mode cell sickle with echocardiography was From the Department of Obstetricsand Gynecology,Bowman Gray School of Medicine of Wake Forest University. Supported in part by National Institutes of Health, Natumal Heart, Lung, and Blood Institute grant No. HL38296 (/. C. V.).
Received for publication May 10,1993. August accepted
17,1993;
revised July
30,1993;
Reprint requests:Jean-Claude Vedle, MD, Department of Obstetrics Bowman Gray School GynecologX of Medicine, Winston-Salem, and NC 27157. Copyright © 1994 by Mosby-Year Book, Inc. 0002-9378/94 $1.00 + .20 6/1/50628
used to document left ventricular size and function during systole and diastole. A group of normal patients were used for comparison during the third trimester of gestation. Method Two-dimensional M-mode echocardiograms with a 3.5 MHz phased-array transducer were obtained in 10 black pregnant patients with homozygous sickle cell anemia and five women with sickle cell-hemoglobin C disease. A group of 40 normal pregnant patients with no complications was also evaluated during the third trimester. All of the patients were normotensive and had no cardiovascular disease. The only medication taken by the subjects were prenatal vitamins. Informed consents previously approved by the Institutional Review Committee of the hospital were obtained before the study. M-mode echocardiograms were obtained using an ATL UN19 (Advanced Technology, Bothell, `Nash.). All patients were studied in the left lateral decubitus position after a 15-minute rest. M-mode echocardiography has previously been described and has been found to be a reliable and acceptable noninvasive method to assesscardiac function during preg-
107
108
Veille and Hanson
January 1994 Am J Obstet Gynecol
Table I. Results (means ± SEM) I
Variable
Control
Heart rate (beats/min) Mean arterial pressure (mm Hg) End-diastolic dimension (mm) Left atrium (mm) Left ventricle posterior wall thickness diastole (mm) Interventricular septum diastole (mm) Mass (gm) Fractional shortening (%) Stroke volume (ml) Cardiac output (Umin) Total peripheral resistance (dynes " sec " cm Hemoglobin (%)
86.6 69.5 49.4 35.2 7.1
± ± ± ± ±
1.8 0.9 0.7 1.1 0.2
8.4 141.9 37.9 72.3 6.395 939.6 11.9
± ± ± ± ± ± ±
0.3 9.0 0.9 3.1 0.28 49.3 0.1
Sickle cell 78.5 67.7 52.7 38.3 11.7 11.7 303.7 38.7 91.3 7.596 780.8 8.7
± ± ± ± ±
6.3 1.8 1.5 1.6 0.5
± 0.4 20.9 ± 1.8 ± 6.7 ± 0.54 ± 80.9 ± 0.2
Significance NS NS p<0.03 NS p<0.00001 p<0.00001 p<0.00001 NS p<0.05 p<0.03 NS p<0.0001
NS, Not significant.
nancy. ' Briefly, the transducer was placed in the left third or fourth intercostal space to obtain a long axis The M-mode view of the left ventricle. cursor was positioned at the level of the chordae tendinea and moved toward the annulus to obtain views of the left cavity with a flick of the mitral valve. " A ventricular sweep of the left ventricle was then obtained, and to the left atrium were recorded on a strip chart at a speed of 50 mm/sec. Left dimensions obtained from the ventricular end-diastolic onset of QRS complex and the end-systolic dimensions returning
echoes perpendicular
at the end-diastolic nadir of the septal motion, according to recommendations made by Sahn et al., ' Six consecutive were analyzed. cardiac cycles were obtained
measured
and
averaged. The following (1) left ventricular volume
calculations
were obtained: or end-systolic volume = 7D/2.4 + D, where D= end-diastolic dimension (2) stroke volor end-systolic dimensions, ume = end-diastolic volume - end-systolic volume, (3) in dimen(percent change dimensions - end-systolic disions) = end-diastolic dimensions = 100, (4) cardiac mensions/end-diastolic output = stroke volume x heart rate. Left ventricular diastolic function was determined by tracing the septum fractional
shortening
wall from the M-mode hard copy with a digital light pen and graphic overlay. computer-assisted and posterior
Peak filling rate of the left ventricle during diastole, the duration of rapid filling, and the peak rate of systolic thickening and peak rate of diastolic thinning were determined by the interventricular septum and left posterior wall. Total peripheral resistance was obtained as follows: Total peripheral resistance = 80 (Mean blood pressure/Cardiac output), where Mean ventricular
arterial pressure = Systolic +2 Diastolic/3. Statistical between Comparison analysis.
the
two
t test with a groups were made with the unpaired level of 0.05 to reject the null two-sided significance hypothesis. Results are presented as means and SEM.
Results Mean gestational age at the time of this study was not different between the controls and the patients with sickle cell disease (35 ±1 vs 34 -1 weeks, p= not significant). None of the patients had preeclampsia or any hypertensive disorders. Left ventricular M-mode echocardiogram results are shown in Table I. Left ventricular end-diastolic dimension was larger in the sickle cell group, but there was no difference in the left atrial dimensions. Left ventricular wall interventricular septal size during diastole and cardiac mass were significantly greater in patients with sickle cell disease compared with the control group (Table I). Although heart rate and fractional shortening were not different between the two groups, stroke volume and cardiac output were significantly greater in the patients with sickle cell disease. The hemoglobin was significantly lower in the sickle cell patients (8.5% ± 0.2% vs 11.9% ± 0.1%, p<0.0001). Left ventricle diastolic function results are shown in Table II. The peak filling rate of the left ventricle during diastole was significantly lower in the sickle cell group when compared with the normal group (Table II). The duration of rapid filling of the left ventricle was significantly longer in patients with sickle cell disease (Table II). Septal rate of systolic thickening and the rate of septal diastolic thinning was not different between the two groups. Left ventricular posterior wall diastolic thinning was significantly shorter in the patients with sickle cell disease (Table II). No abnormality of the normalized peak rate of systolic thickening was found during the analysis of either septal or left posterior wall motion. There was no difference in the total peripheral resistance between the normal and the patients affected by sickle cell disease (938.6 ± 49.3 vs 780.8 ± 80.9 dynes - sec - cm-'). There was no significant difference in either measured or derived cardiovascular parameters between the patients affected by SS or SC disease.
Veille and Hanson
Volume 170, Number 1, Part I Am J Obstet Gynecol
109
Table II. Diastolic values (mean ± SEM) Control Left ventricle Left ventricular diastolic relaxation-diastole (cm/sec) Duration of rapid filling (msec) Septum Normalized peak rate of systolic thickening second Normalized peak rate of diastolic thinning second Posterior wall Normalized peak rate of systolic thickening second Normalized peak rate of diastolic thinning second
per per
per per
Sickle cell
Significance
14.6 ± 0.9
11.5 t 0.5
p<0.03
165.8 ± 7.8
205.7 ± 12.3
p<0.009
2.8 ± 0.1
2.4 ± 0.2
NS
2.8 ± 0.1
2.3 ± 0.3
NS
5.3 ± 0.4
4.4 ± 0.5
NS
8.5 ± 0.9
5.1 ± 0.7
p<0.02
NS, Not significant.
Comment During the third trimester of pregnancy left ventricular end-diastolic dimension was significantly greater in disease than by a normal pregcell with sickle patients left The group. ventricles of patients with control nant thicker, which in sickle cell disease were significantly diastolic relaxation. The turn affected left ventricular disease left in the atrium patients sickle cell with of size larger than that of the control was not significantly difference in hemoIn the spite of a significant group. globin level between the two groups, heart rate and between the fractional shortening were not different larger stroke volume and groups. The significantly found in the patients with sickle cell output cardiac disease is secondary to the increase in end-diastolic dimension and is not because of increases in heart rate '° This reflects an adequate fractional shortening. or adjustment to chronic anemia. The peak both thickening the interventricular of systolic rate of left posterior wall was not different in the and septum for dimension. both groups, even when normalized
hemodynamic
The diastolic relaxation of the left ventricle was sigin disease, decreased the group with sickle cell nificantly longer for filling in time the rapid a of resulted which diastolic Although septal relaxation and that chamber. by this state of affected not were thickening systolic diastolic thinning of the posterior the anemia, chronic disease. in lower the with sickle cell patients wall was This abnormal diastolic relaxation can be secondary to decreased ventricular compliance or impaired left venischemia, Preload, myocardial tricular contractile state. or even atrial contraction abnormality may all play a diastolic in the observed ventricular significant role filling. The abnormal diastolic function found in these by left likely is ventriccaused most pregnant patients left in increase by hypertrophy the ventricular and ular
mass. The most likely explanation for this hypertrophy is local ischemic changes secondary to either chronic anemia, sickling, or obstruction of the microcirculation, rather than in a response to an increase in systemic vascular resistance. Thus, in pregnant patients with sickle cell disease, systolic function was found to be normal, but diastolic ventricular relaxation was found to be impaired. This study demonstrates that the increased cardiac output requirements that occur during pregnancy are met by a greater increase in left ventricular end-diastolic dimension. Although we demonstrated diastolic relaxation differences of the left ventricle in these patients at rest, these changes do not seem to affect left ventricular systolic function and output. In children with sickle cell disease left ventricular mass was found to increase when enlargement of the left ventricle could defor the not adequately compensate myocardium mands. " In adults with sickle cell disease the normalized rate of change of the left ventricular cavity dimension in diastole was significantly lower when compared with a group of normal controls. Left posterior wall relaxation when normalized for dimension was also " Although lower in the cell group. sickle significantly we found similar findings in a pregnant population with left in decrease disease, ventricle complithe sickle cell ance did not result in an abnormal volume-length has been assoleft which the ventricle, relationship of " dysfunction. It is always possible ciated with cardiac that such diastolic dysfunction could eventually result in systolic dysfunction and abnormal ejection fraction or wall motion abnormality during periods of cardiac stress or exercise, as has been reported. ' Our study demonstrates that these patients adapt well to pregnancy and that accessory mechanisms such as heart rate or fractional shortening used normally to maintain or to
110 Veille and Hanson
increase cardiac output during acute anemia are not required under normal conditions in the third trimester in these patients with chronic anemia. Covitz et al. 'Y found that the septum was hypertrophied in patients with sickle cell disease. Such abnormality in the septal relaxation may be related to biventricular wall stress and may in turn affect diastolic filling and normal ventricular emptying or filling. " In the current study we also found significant septal hypertrophy, which could have affected ventricular filling without affecting ventricular systolic function and cardiac output. Thus these patients have slowed relaxation and decreased diastolic distensibility, which eventually can result in an elevation of filling pressures and in an inability of the ventricle to fill during diastole. These abnormalities in diastolic filling may in turn influence systolic pump function and may cause pulmonary congestion during such stress periods as exercise and episodes of tachycardia. The presence of diastolic abnormality in these pregnant patients, however, should alert the obstetrician to the possibility that labor or the postpartum period may put these patients at a greater risk for cardiovascular stress. This study supports our original hypothesis that sickle cell disease significantly affects the systolic and diastolic function of the left ventricle during pregnancy. In spite of some diastolic dysfunction these patients can adequately adjust to the cardiovascular stress of pregnancy, and they appear to have no impairment of the left ventricular systolic function. To properly document the effect of pregnancy on cardiac function in patients with sickle cell disease, a study should be conducted to compare the same patients in a nonpregnant state. We thank Dr. W. Covitz for reviewing and analyzing our data.
January 1994 Am J Obstet Gynecol
REFERENCES 1. Fort AT, Morrison JC, Berreras L, Diggs LW, Fish SA. Counselling the patient with sickle cell disease about reproduction: pregnancy outcome does not justify the maternal risk. A.M J Ousrsr GYNECOL1971; 111: 324-7. 2. Hendricks JP, de V Harrison KA, Watson-Williams EJ, Luzzatto L, Ajabor LN. Pregnancy in homozygous sickle cell anemia. J Obstet Gynecol Br Commonw 1979; 79: 396409. 3. Milner PF, Jones BR, Döbler J. Outcome of pregnancy in sickle cell anemia and sickle cell hemoglobin C disease. A.H J Oesrer GYNECOL1980; 138:239-45. 4. Powars DR, Sandhu M, Niland-Weiss J, Johnson C, Bruce S, Manning PR. Pregnancy in sickle cell disease. Obstet Gynecol 1986; 67: 217-28. 5. Gerry JL, Bulkley BH, Hutchins GM. Clinicopathologic analysis of cardiac dysfunction in 52 patients with sickle cell anemia. Am J Cardiol 1978;42: 211-6. 6. Balfour IC, Covitz W, Arensman FW, Eubig C, Garrido M, Jones C. Left ventricular filling in sickle cell anemia. Am J Cardiol 1988; 61: 395-9. 7. Veille JC, Morton MJ, Paul MS. Maternal left ventricular dimension in pregnancies complicated by fetal growth retardation. Obstet Gynecol 1991; 78: 265-9. 8. Popp RI, Filly K, Brown OR, Harrison DC. Effect of transducer placement on echocardiographic measurements of left ventricular dimensions. Am J Cardiol 1975; 35: 537-40. 9. Sahn DJ, DeMaria A. Kisslo J, et al. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978; 58: 1072-7. 10. Gibson DG, Traill TA, Hall RJC, Brown DJ. Echocardiographic features of secondary left ventricular hypertrophy. Br Heart J 1979; 41: 54-9. 11. Balfour IC, Covitz W, Davis H, Syamasundar R, Strong WB, Alpert BS. Cardiac size and function in children with sickle cell anemia. Am Heart J 1984; 108:345-50. 12. Covitz W, Eubig C, Balfour IC, et al. Exercise-induced cardiac dysfunction in sickle cell anemia: a radionuclide study. Am J Cardiol 1983; 51: 570-5. 13. Grossman W, MeLaurin L. Diastolic properties of the left ventricle. Ann Intern Med 1976;84: 316-26.