Research on hypertrophic cardiomyopathy and cardiac function by ultrasound in fetuses of diabetic mothers

o - VTI (cm) 8,0 ± 0,42 9,6 ± 1,35 11,2 ± 1,15 0,000 PA - VTI (cm) 7,1 ± 0,38 7,8 ± 0,54 9,5 ± 0,84 0,000 MV - S’(cm/s) 3,8 ± 0,51 4,0 ± 0,52 4,2 ± 0,64 0,000 TV - S’(cm/s) 5,2 ± 0,81 5,4 ± 0,89 5,9 ± 1,13 0,005 LV - IVCT(ms) 35,0 ± 3,61 37,5 ± 5,99 37,0 ± 3,16 0,432 RV - IVCT(ms) 39,0 ± 5,01 39,0 ± 5,86 38,0 ± 6,68 0,894 LV - FS (%) 34,0 ± 4,67 35,5 ± 5,44 35,0 ± 4,66 0,206 Diastolic cardiac function MV - E/A 0,67 ± 0,04 0,74 ± 0,05 0,77 ± 0,05 0,000 TV - E/A 0,74 ± 0,04 0,76 ± 0,05 0,79 ± 0,72 0,000 MV - E’/A’@ 0,74 ± 0,07 0,81 ± 0,07 0,82 ± 0,06 0,000 TV - E’/A’ 0,72 ± 0,06 0,76 ± 0,09 0,78 ± 0,09 0,003 LV - IVRT (ms) 39,0 ± 4,81 41,0 ± 5,94 42,0 ± 5,94 0,137 RV - IVRT (ms) 40,0 ± 6,28 42,0 ± 6,47 42,0 ± 5,12 0,228 Overall cardiac function LV - MPI 0,38 ± 0,04 0,37 ± 0,04 0,38 ± 0,04 0,116 RV - MPI 0,39 ± 0,03 0,38 ± 0,03 0,41 ± 0,04 0,117 Table 3.5. Correlation coefficient between fetal cardiac function and gestational age in control group. Correlation coefficient (r) Variables By week By month Variables By week By month Systolic cardiac function Diastolic cardiac function Ao - VTI 0,807* 0,728* MV - E/A 0,476* 0,546* PA - VTI 0,830* 0,749* TV - E/A 0,450* 0,485* MV - S’ 0,321* 0,269* MV - E’/A’@ 0,397* 0,384* TV - S’ 0,244* 0,230* TV - E’/A’ 0,213* 0,206* LV – IVCT 0,083 0,097 LV - IVRT 0,124 0,149 RV - IVCT -0,025 -0,002 RV - IVRT 0,005 0,124 LV - FS 0,055 0,045 Overall cardiac function @: standard variables, (*): correlation coefficient is statistically significant LV - MPI 0,037 0,057 RV - MPI -0,048 -0,011 Ao(aortic valve) VTI (velocity time integral), PA( pulmonary valve), MV(mitral valve), TV(tricuspid valve), S’(systolic tissue velocity), LV(left ventricle), RV(right ventricle), IVCT(isovolumetric contraction time), FS(fraction shortening), IVRT(isovolumetric relaxation time), MPI(myocardial performance index) Comments on table 3.4 and table 3.5:  Systolic cardiac function:  Increased Ao-VTI, PV-VTI reflect an increase in the volume of the squeeze in the absence of blood flow obstruction. These two indicators increased significantly by gestation week, closely correlated with gestational age.  MV-S’, TV-S’ reflect the systolic function due to intrinsic contraction ability of myocardium, also increased gradually, averagely correlating with gestational age. 10  LV-IVCT, RV-IVCT are the acceleration of myocardium, reflecting the systolic function due to the intrinsic ability of myocardium. These two indices did not change and did not correlate with gestational age in the last trimester.  LV- FS reflects total systolic function, whether due to changes in preload or internal myocardium. This index was also not changed by pregnancy week, not correlated with gestational age in the last trimester.  Diastolic cardiac function  The ratio of E/A and E'/A' of left and right ventricle increased gradually with gestational week, reflecting the maturation of diastolic function. The linear average correlation but weak with gestational age in the last trimester.  LV-IVRT, RV-IVRT are relaxation times of the ventricles, reflecting the diastolic function of the ventricles without relying on loading. These indices did not change and correlate with gestational age in last trimester.  Overall cardiac function:  LV-MPI, RV-MPI are indicators reflecting systolic and diastolic function, unchanged and did not correlat with gestational age in the last trimester. 3.3. The prevalence, characteristics of fetal HCM and cardiac function of diabetic mother. 3.3.1. The prevalence and characteristics of HMC in fetuses of diabetic mothers 3.3.1.1. The prevalence of fetal hypertrophic myocardiopathy  According to type of diabetic mother and the severity of HbA1C Chart 3.6. The prevalence of fetal HCM according to type of DM & HbA1C Comments: The prevalence of fetal HCM in general diabetic group was 43,2%, increased in pregestational diabetes (66,1%), and in group with HbA1C ≥ 6% (69,7%).  According to the combined clinical factors of the mother Chart 3.7. Prevalence of fetal HCM according to the maternal clinical factors 56,8% 61,8% 33,9% 65,4% 30,3% 43,2% 38,2% 66,1% 34,6% 69,7% Diabetic group (n=361) Gestational diabetes (n=296) Pregestational diabetes (n=65) HbA1C < 6% (n=272) HbA1C ≧ 6% (n=89) Non - HCM HCM 59% 43,1% 58,7% 41% 41% 56,9% 41,3% 59% No (n=310) Yes (n=51) No (n=322) Yes (n=39) Diabetic mother combined obesity Diabetic mother combined over weight gained Fetal Non - HCM Fetal HCM 11 Comments: The prevalence of fetal HCM was significantly increased in obese mothers was 56,9% and in over-weight gain during pregnancy was 59% compared to the rest (p <0,05)  According to fetal weight Chart 3.8.The prevalence of fetal HCM according to fetal weight Comments: The prevalence of fetal HCM in the macrosomia group was 55,6%, significantly higher than the other groups (p <0,05). 3.3.1.2. Characteristics of HMC in fetuses of diabetic mother  The severity of fetal cardiac wall thickness Chart 3.9. The severity of fetal cardiac wall thickness in diabetic group Comments: The absolute absolute cardiac thicknesses were not too thick, there was no case of obstruction of the outflow of ventricles. Beside that, 19,7% and 21,6% of fetuses increased cardiac wall thickness at ≤ 1SD and 1-2SD.  Hypertrophic region Chart 3.10. The prevalence of HCM by region of hypertrophy 60% 59,9% 44,4% 40% 40,1% 55,6% Low weight (n=15) Normal weight(n=292) Macrosomia (n=54) Fetal HCM Fetal non-HCM 26,9% 28,5% 25,5% 15,5% 23,8% 19,4% 23,8% 19,7% 16,3% 21,3% 16,1% 21,6% 33% 30,7% 34,6% 43,2% RVW LVW IVS Common Normal ≤ 1SD 1SD - 2SD > 2SD 5,4mm 4,9mm 5,6mm 70,5% 76,2% 80% 24% 25% 51% LVW RVW IVS 1 region 2 regions 3regions Hypertrophic region Number of hypertrophic region P e rc e n ta ge 12 Comments: the percentage of hypertrophy in IVS was highest (80%) and the hypertrophy of all 3 cardiac walls was the most (51%). 3.3.2. Manifestations of cardiac function in fetuses of diabetic mother 3.3.2.1. Manifestations of systolic function Table 3.6. Systolic function of the fetuses in diabetic group Variables Controls (n=178) Categorize fetuses of diabetic group according to the fetal HCM Non-HCM (n=205) HCM (n=156) 28-31+6 week n 55 80 86 Ao - VTI (cm) 8,0 ± 0,42 8,4 ± 0,95* 9,25 ± 1,66*# PA - VTI (cm) 7,1 ± 0,38 7,4 ± 0,44* 8,4 ± 1,47*# MV - S’(cm/s) 3,8 ± 0,51 3,8 ± 0,33 4,0 ± 0,40*# TV - S’(cm/s) 5,2 ± 0,81 5,3 ± 0,29 5,4 ± 0,38*# LV - IVCT(ms) 35,0 ± 3,61 36,0 ± 2,25 37,0 ± 1,54*# RV - IVCT(ms) 39,0 ± 5,01 39,0 ± 3,52 39,0 ± 4,52 LV - FS (%) 34,0 ± 4,67 35,0 ± 3,28 35,0 ± 3,22 32-35+6 week n 92 102 59 Ao - VTI (cm) 9,3 ± 1,35 9,5 ± 1,07 11,1 ± 1,33*# PA - VTI (cm) 7,8 ± 0,54 8,15 ± 0,93* 9,6 ± 1,27*# MV - S’(cm/s) 4,0 ± 0,52 4,1 ± 0,49 4,3 ± 0,48* TV - S’(cm/s) 5,4 ± 0,89 5,4 ± 0,36 5,5 ± 0,37# LV - IVCT(ms) 37,5 ± 5,99 37,0 ± 1,77 38,0 ± 1,23# RV - IVCT(ms) 39,0 ± 5,86 39,0 ± 0,89 40,0 ± 1,30*# LV - FS (%) 35,5 ± 5,44 35,0 ± 3,14 35,0 ± 3,08 36-39+6 week n 31 23 11 Ao - VTI (cm) 11,2 ± 1,15 11,4 ± 0,84 12,5 ± 1,78* PA - VTI (cm) 9,5 ± 0,84 9,8 ± 0,77 10,3 ± 1,67* MV - S’(cm/s) 4,2 ± 0,64 4,3 ± 0,22 4,5 ± 0,69# TV - S’(cm/s) 5,9 ± 1,13 6,1 ± 0,28 6,2 ± 0,34 LV - IVCT(ms) 37,0 ± 3,16 37,0 ± 1,44 39,0 ± 1,62# RV - IVCT(ms) 38,0 ± 6,68 39,0 ± 0,87 40,0 ± 0,75*# LV - FS (%) 35,0 ± 4,66 34,0 ± 3,38 34,0 ± 2,46 Ao(aortic valve) VTI (velocity time integral), PA( pulmonary valve), MV(mitral valve), TV(tricuspid valve), S’(systolic tissue velocity), LV(left ventricle), RV(right ventricle), IVCT(isovolumetric contraction time), FS(fraction shortening), (*): Significantly different from control group , (#):Significantly different from non –HCM group Comments:  Compared to control group, in non-HCM fetuses of diabetic group, changes in systolic function was associated with a significant increased in simple VTI, especially PA- VTI, without differences in the rest of systolic index.  In HCM fetuses of diabetic group, both of apparent increased in VTI, myocardial velocity (MV-S', TV-S') and isovolumetric time (LV-IVCT, RV- IVCT) also increased, and were significantly higher than that of non-HCM and control group.  FS was within normal limits and no difference between study groups 13 3.3.2.2. Manifestations of diastolic function and overall cardiac function Table 3.7. Diastolic function and overall cardiac function of the fetuses in diabetic group Diastolic and overall cardiac function variables Controls (n=178) Categorize fetuses of diabetic group according to the fetal HCM Non - HCM (n=205) HCM (n=156) 28-31+6 week n 55 80 86 MV - E/A@ 0,67 ± 0,04 0,69 ± 0,04 0,66 ± 0,04# TV - E/A 0,74 ± 0,04 0,76 ± 0,04* 0,74 ± 0,04# MV - E’/A’ @ 0,74 ± 0,07 0,71 ± 0,05* 0,70 ± 0,05* TV - E’/A’ 0,72 ± 0,06 0,71 ± 0,05* 0,70 ± 0,04* LV - IVRT (ms) 39,0 ± 4,81 39,0 ± 0,94 41,5 ± 3,92*# RV - IVRT (ms) 40,0 ± 6,31 40,0 ± 1,26 43,0 ± 4,22*# LV - MPI 0,37 ± 0,04 0,38 ± 0,02 0,42± 0,04*# RV - MPI 0,39 ± 0,03 0,39 ± 0,01 0,43 ± 0,04*# 32-35+6 week n 92 102 59 MV - E/A@ 0,74 ± 0,05 0,74 ± 0,03 0,71 ± 0,04*# TV - E/A 0,76 ± 0,05 0,77 ± 0,03 0,76± 0,06* MV - E’/A’ @ 0,79 ± 0,07 0,76 ± 0,06* 0,73 ± 0,05*# TV - E’/A’ 0,76 ± 0,07 0,74 ± 0,03* 0,73 ± 0,04* LV - IVRT (ms) 41,0 ± 5,94 40,0 ± 1,16 43,0 ± 3,72*# RV - IVRT (ms) 42,0 ± 6,47 42,0 ± 1,25 45,0 ± 3,71*# LV - MPI 0,36 ± 0,04 0,38 ± 0,02 0,44 ± 0,04*# RV - MPI 0,38 ± 0,01 0,40 ± 0,01 0,46 ± 0,04*# 36-39+6 week n 31 23 11 MV - E/A@ 0,77 ± 0,05 0,77 ± 0,03 0,73 ± 0,06*# TV - E/A 0,79 ± 0,07 0,80 ± 0,04 0,79 ± 0,06 MV - E’/A’ @ 0,82 ± 0,06 0,80 ± 0,05 0,76 ± 0,06# TV - E’/A’ 0,76 ± 0,09 0,74 ± 0,06 0,75 ± 0,03 LV - IVRT (ms) 42,0 ± 5,94 42,0 ± 1,72 47,0 ± 3,76*# RV - IVRT (ms) 42,0 ± 5,12 42,0 ± 2,19 42,0 ± 4,50*# LV - MPI 0,38 ± 0,04 0,40 ± 0,03 0,49 ± 0,04*# RV - MPI 0,41 ± 0,04 0,41 ± 0,03 0,51 ± 0,04*# (@):expressed as mean ± standard deviation (*): Significantly different from control group (#):Significantly different from non – HCM group Comments:  In the non HCM fetus of diabetic group, there was a significant decrease in diastolic function, manifested by a simple decrease of E/A and E'/A' in both ventricles compared to control group, while MPI only increased significantly at 32- 35 +6 weeks of gestation.  In the HCM fetuses of diabetics group, the right ventricular and left ventricular diastolic function were significantly reduced, not only decreased the ratio of E/A and E'/A' but also significantly increased IVRT of both ventricles. The MPI of right ventricle and left ventricle decreased significantly compared to other group. 14  The prevalence of decreased overall cardiac function in fetuses of diabetic mothers Chart 3.11. Prevalence of overall cardiac dysfunction in fetuses of diabetic mothers Comments: The prevalencw of the decreased overall cardiac function of the fetuses of diabetic mothers was 40,8%, higher in the HCM fetus group (79.8%) 3.4. Relationship between some factors of mother and fetuses to fetal HCM 3.4.1. Relationship between some maternal factors and fetal HCM Factors included maternal weight, HbA1C and treatment of maternal hyperglycemia. 3.4.1.1. Relationship between maternal weight, HbA1C and fetal HCM Table 3.8. Relationship between maternal weight, HbA1C and fetal HCM Some factors of mother The fetal HCM Univariate analysis Multivariate OR 95%CI OR 95%CI Obesity before pregnancy 1,89 1,04 - 3,45 1,41 0,74 - 2,69 Over-weight gain during pregnancy 2,04 1,03 - 4,01 1,47 0,71 - 3,03 HbA1C ≥ 6,0% 4,34 2,59 - 7,28 3,99 2,36 - 6,76 Comments:  The univariate analysis showed that the risk of developing HCM in the fetuses of diabetic mother with obesity, over-weight gain in pregnancy and had HbA1C ≥ 6% was 1,89 times higher than the cases of mothers with diabetes without obesity, was 2,04 times higher than pregnant women without overweight gain and 4,34 times than mothers with HbA1C below 6%.  Results of multivariate analysis showed that the risk of developing fetal anomalies in mothers with HbA1C ≥ 6% was 3,99 times higher than that of mothers with diabetes and HbA1C <6%, when there was an interaction of other factors such as obesity or over-weight gain during pregnancy. 59,2% 83,1% 20,2% 40,8% 16,9% 79,8% Diabetic group (n=361) non - HCM - diabetic group (n=205) HCM - diabetic group (n=156) Normal overall cardiac function Reduced overall cardiac function 15 Chart 3.12. Prognostic value of HbA1C with fetal HCM of diabetic mother (n = 361, AUC = 0,753; Sensitivity = 59%, Specificity = 97,5%, cutoff value = 6,1%, PR2 = 18%) Comments: With an HbA1C value from over 6,1%, it was likely to predict the development of HCM in the fetus whose mother has diabetes during pregnancy with sensitivity = 59%, specificity = 97,5% and the AUC = 0,753. 3.4.1.2. Relationship between diabetes treatment in pregnancy and fetal HCM 361 women with gestational diabetes were managed in the Department of Endocrinology and Obstetrics Department of Bach Mai Hospital, in which, 240 fetuses received FE at least 2 times with the average follow-up period of 5,02 weeks. Chart 3.13. Variations in fetal HCM frequency in the treatment group Chart 3.14. Variations in fetal cardiac function in the treatment group Comments: Treatment of hyperglycemia during pregnancy significantly reduced the prevalence of HCM and overall cardiac function reduction in fetuses of diabetic mother, this result appeared in both diet-adjusted and insulin group. 3.4.2. Relationship between some fetal clinical factors and fetal HCM 3.4.2.1. Relationship between fetal weight and fetal HCM Table 3.9. Relationship between fetal weight and fetal HCM Fetal weight Fetal HCM OR 95%CI Macrosomia 1,8 1,02 - 3,21 Comments: The univariate analysis showed that the risk of developing HCM in the fetus was 1,8 times than in the case of non-large fetuses and the difference was statistically significant with 95% confidence level. 16 3.4.2.2. Relationship between fetal HCM and the postnatal outcomes. All 511 fetuses were clinically monitored postnatal through patient questions, direct examinations and medical records. Table 3.10. Relationship between fetal HCM and the postnatal outcomes. Postpartum outcome variables Categorize fetuses of diabetic group according to the fetal HCM (n=361) Non- HCM (n=205) HCM (n=156) P value OR (95%CI) Preterm birth (n,%) No 195(95,1) 139(89,1) 0,031 2,38 (1,06-5,36) Yes 10(4,9) 17(10,9) Low birth weight (n,%) No 198(96,6) 142(91) 0,025 2,78 (1,09-7,08) Yes 7(3,4) 14(9) Cesarean section due to fetal failure (n,%) No 202(98,5) 149(95,5) 0,083 3,16 (0,80-12,4) Yes 3(1,5) 7(4,5) 1 st minute Apgar score ≤ 7 (n,%) No 199(97,1) 143(91,7) 0,023 3,01 (1,11-8,12) Yes 6(2,9) 13(8,3) Perinatal deaths (n,%) 0 0 Comments:  The percentage of preterm birth was significantly higher among the diabetic group. The risk of preterm birth in a HMC fetuses was 2,38 times higher than in the cases of non-HCM group.  The percentage of low birth weight of the HCM group was much higher than the non-HCM group (p = 0,025). The risk of low birth weight in HCM group increased by 2,78 times compared with non-HCM group.  The method of cesarean section due to fetal failure was not significantly different between the diabetic group with HCM and without HCM.  The percentage of fetuses with low 1st minute Apgar score ≤ 7 in HCM group was significantly higher than non-HCM group (p = 0,023). The risk of low 1 st minute Apgar score ≤ 7 in the HCM fetuses were increased by 3,01 times compared with non-HCM fetuses.  There was no perinatal death during the study period. Chapter 4: DISCUSSION 4.1. General characteristics of the study groups 4.1.1. General characteristics of controls and disease groups Our study had a similarity in gestational age, which helped to partially eliminate the effect of this factor on fetal development in the uterine. In addition, for the risk factors for diabetes during pregnancy, only the history of miscarriage or stillbirth of diabetic group was significantly higher than the controls. Meanwhile, the rate of anemia, increased cholesterol and triglycerides of pregnant women at the time of the study were 7,8%, 76,5% and 75% similar to the study of Hiramatsu Y et al (2012), Barrett HL et al (2014) in healthy pregnant women, and there was no difference between the control and diabetic group. This may help limit the effects of physiological anemia as well as lipid 17 metabolism disorders on fetal myocardium, which has been reported in several previous studies. The average HbA1C of the disease group was not too high (5,6 ± 0,85,%) and was the only subclinical index that was different from controls (table 3.1). The fetuses in the study had an average gestational week at the start of the study which was 32,3 ± 3,28 (weeks), dispersed from week 28 to week 39, but focused mainly on fetal weeks 28 and 32 (chart 3.1), because this was the time for the women usually checking for blood glucose tolerance test and birth registration. The average gestational weight of the groups in the study increased linearly with the gestational week and was only actually larger in the gestational group at gestational weeks 29, 31 and 36 (chart 3.2). The uniformity and fluctuation within the normal range of fetal heart rate in chart 3.3 would help to limit errors in measurement of cardiac function in the fetus. 4.1.2. Unique characteristics of diabetic group Compared with gestational diabetes, pre-gestational diabetes poses a higher risk for fetal heart disease Of the 361 women with diabetes during pregnancy, only 65 (18%) of diabetic mothers actually were gestational diabetes. Because the average HbA1C level of the disease group was not too high (5,6±0,85,%), based on the goal of controlling blood glucose for diabetic mother if there is no sign of hypoglycemia of ADA 2017 is HbA1C <6%, and based on the recommendation of the American Heart Association fetal echocardiography for diabetic mother with HbA1C ≥ 6% in the last trimester, we chose upper and lower HbA1C threshold 6% to clarified risk group for diabetic mother. The results presented in chart 3.4 showed that the blood glucose level of disease group in our study was not too high with the proportion of diabetic mother having HbA1C blood ≥ 6%, accounting for only 24,7%. This was probably because 39,5% of pregnant women in the moderate risk group, while cases of stillbirth due to complications of maternal hyperglycemia without previous FE were excluded from the study. Along with the development of obesity was the explosion of gestational diabetes, the obesity rate of diabetic group was 14,1% higher than previous studies. In addition, according to Scifres, CM et al (2014), excessive weight gain during pregnancy was also a risk factor for causing a macrosomia. And in our study, the over-weight gain rate during pregnancy was 10,8%. Hyperglycemia in the third trimester of pregnancy had been shown to be one of the major risk of fetal macrosomia, and in our study, the rate of macrosomua in diabetic group was 15%. Thus, the blood glucose level of the disease group in our study was not too high, however, the proportion of pregnant women with a combination factor such as obesity, over-weight gain in pregnancy also accounted for to 14,1% and 10,8%. Especially, up to 15% of fetuses in the disease group were "larger than the gestational age". 4.2. Characteristics of fetal cardiac thickness and cardiac function in controls In this study, we chose a cross-sectional study to establish normal values of fetal cardiac thickness and function by the last trimester of pregnancy for the following reasons: firstly, only ultrasound survey in line with the recommendations of the World Association of Obstetrics and Gynecology, secondly, the data collection is easier with the best statistical strength because 18 the data is more representative for the surveyed population. And to overcome the disadvantage that is difficult to control in the fetus with abnormal development later, we only included studies of fetuses who met the postpartum selection criteria. However, there were 28 cases having the second FE control group after an average of 5,02 weeks to ensure adequate normal data as a basis for comparison for the disease group in late pregnancy (after 36 weeks). Therefore, although there were 178 FE records of the control group, it represented only 150 normal fetuses and this is one of the limitations of this study. However, 150 normal fetuses still be enough to match the sample size requirements of the control. 4.2.1. Characteristics of fetal cardiac wall thickness in control group During the last trimester of pregnancy, fetal myocardial cells continue to grow in quality, so the cardiac wall thickness of the heart increases in response to changes in preload and afterload. In the fetal circulation, the right ventricle is predominantly working than the left ventricle so the thickness of RVW is thicker than LVW, while IVS is the myocardial region under the interaction of the two ventricles in pressure and volume, so it is usually thicker than other ventricular walls. Our research results showed that, the average cardiac wall thickness in both systole and diastole of the control groups increased gradually by gestational week, in which the IVS thickness was the most dominant, followed by RVW, and LVW was smallest (table 3.2). In addition, both cardiac and diastolic cardac wall thickness were strongly and linearly correlated with gestational week and fetal weight (table 3.3), consistent with the regression model of the size of the cardiac wall according to gestational age by Le Kim Tuyen et al (2014). The results of IVS thickness in our study was similar to those of Veille et al (1996), Lawan Patchakapat MD et al (2006) when evaluating the same gestational age and technique using. 4.2.2. Characteristics of fetal cardiac function in control group. As with the thickness of the cardiac wall, parameters that reflect systolic function also increase with fetal heart maturation, in order to accommodate the increase in preload and post-shift changes. Increasing the velocity of blood flow over time (VTI) through the aortic valve and aortic valve indicates an increase in preload in the absence of obstruction of the ventricular ejection pathway. Besides, increasing the maximum myocardial velocity in the systolic (S wave) due to the maturation of myocardial intrinsic also reflects the improvement in systolic function in the third trimester of pregnancy. Results of our study that presented in tables 3.4 and 3.5 showed that the PA-VTI, Ao-VTI increased significantly and correlated linearly with gestational week, MV-S', TV-S' also increased by week, but with the moderate correlation, while the time of isovolumetric contraction of the right ventricle and left ventricle (RV-IVCT, LV- IVCT) and left ventricular fraction shortening (FS) fractions reflects total systolic function even due to changes in loading and myocardial intrinsic, almost not change and not correlation with gestational week. The above results were quite similar with some previous studies such as Maria Ame’lia et al (2008), CHU chen et al (2012), Sevket Balli vs cs (2013). In the last trimester, immaturity of myocardial cells and fetal heart architecture has created a pattern of physiologically impaired relaxation, expressed as an E/A ratio of always less than 1. As normal pregnancy progresses, the preload increases while afterload decreases and the ability to expand 19 myocardium increases, so the E/A ratio increases during pregnancy, however, this indicator is prone to affected by loading. Similar to the E/A ratio, the E’/A’ ratio also increased due to the increase in rapid filling that explained by the improvement in active cardiac relaxation. At any gestational week, the ratio of E/A, E'/A' of the right ventricle are always higher than the left ventricle because the vertical distribution of myocardial fibers in RVW differs from the distribution of periodic muscle fibers in IVS, or evenly distributed vertical and circumference in the