Evaluation Of Fetal Cardiac Function By Brain Natriuretic Peptide And Velocity Vector Imaging

BackgroundBrain natriuretic peptide (BNP) is a 32-amnio acid polypeptide mainly secreted by ventricular myocytes. This peptide will be activated by increased ventricular stretch and wall tension. It induces vasodilation; inhibits the rennin-angiotensin-aldosterone axis and angiotensin production; blocks cardiac sympathetic nervous system activity; and increases diuresis. Recently, BNP have been widely considered as excellent markers in the diagnosis and therapy and prognosis of adult cardiovascular diseases. Plasma BNP had been reported that it had linear relationship with left ventricular end-diastolic pressure and left ventricular wall extension, and correlated closely to the stratification of cardiac function of heart failure. Currently, the measurement of brain natriuretic peptide could be supplement to echocardiographic in clinical practice. A latest paper established an animal model with aortic stenosis, which showed that the concentration of BNP in fetal amniotic fluid (AF) was correlated closely to ventricular hypertrophy and BNP concentrations in hydropic fetuses were statistically different from compensatory hypertrophy fetus, so amniotic fluid BNP concentrations correlate with the severity of fetal aortic stenosis. However, there is litter research about BNP concentrations of human fetal cardiac dysfunction. Congenital heart disease (CHD) is a kind of common congenital malformation. With the development of devices and skill, the birth rates get to rise of fetuses with non-fetal congenital heart disease. As we all know, the changes of fetal cardiac function may reflect fetal wellbeing intrauterine and prognosis, so appropriated evaluation of fetal cardiac function is very important.Velocity vector imaging (VVI) is a newly developed offline analysis software package that allows evaluation of myocardial tissue motion and velocity without the limitations of Doppler echocardiography. It allows an intuitive analysis of myocardial mechanics by longitudinal and radial and circle axis. This technology has commonly applied in adult heart disease. Our experiments previously had demonstrated that VVI could play an important role in evaluation of cardiac function in fetuses with congenital heart disease (CHD). The aim of this study is to explore the normal values of BNP in amniotic fluid during the second-trimester and investigate the clinical value of VVI combined with the BNP concentrations to evaluate cardiac function in CHD fetuses.Chapter 1 Preliminary explore of normal values of BNP in amniotic fluid during the second-trimester[Obejctives] The aim of this study is to explore the normal values of BNP in amniotic fluid between 17 and 24 gestational weeks and investigate whether it correlate with gestational weeks.[Methods] Included were normal fetuses who underwent amniocentesis in Shenzhen maternity and child healthcare hospital from April 2010 to December 2010 (the indication of amniocentesis are in accordance with the seventh version of Gynecology and Obstetrics which Lejie to edit in chief). All fetuses were singleton who have two umbilical artery and appropriate for gestational age. We excluded fetuses with structural malformations of the cardiovascular and urogenital system and fetal diseases with potential impact on BNP concentration as follows:tumors, neuromuscular disorders, infections, anemia and hydrops. All participating women gave their written consent and 304 amniotic fluid samples were collected. AF (15ml) was collected in polypropylene tubes that contained protease inhibitor and centrifuged at 1600 g at 4℃for 15 minutes. The supernatant was aliquoted in 1-mL samples and frozen at -70℃until assayed. BNP concentrations were determined according to the manufacturer's instructions with immunoassay kits. Statistical analyses were performed by the SPSS 13.0 software. Kolmogorov-Smirnov test (KS) revealed that BNP concentration is Non-normality distribution. So the values for BNP are shown as media (M) and interquartile range (Q). The Spearman's r coefficient was used to evaluate the correlation between BNP and gestational weeks. P<0.05 was considered statistically significant.[Results]1 304 amniotic fluid samples were collected. Kolmogorov-Smirnov test (KS) revealed that AF BNP concentration is Non-normality distribution. Statistical data reveals that the normal values of AF BNP concentration between 17 and 24 gestational weeks is 0.280-3.123 ng/ml; Media and interquartile range are 1.007 ng/ml and 0.652 ng/ml respectively.2 AF BNP concentration between 17 and 18+6 gestational weeks is 0.374-4.267 ng/ml; Media is 1.154 ng/ml. AF BNP concentration between 19 and 19+6 gestational weeks is 0.199-2.467 ng/ml; Media is 1.040 ng/ml. AF BNP concentration between 20 and 20+6 gestational weeks is 0.294-3.387 ng/ml; Media is 1.073 ng/ml. AF BNP concentration between 21 and 21+6 gestational weeks is 0.270-3.725 ng/ml; Media is 0.930 ng/ml. AF BNP concentration between 22 and 24 gestational weeks is 0.113-2.200 ng/ml; Media is 0.801 ng/ml.3 Significantly difference of AF BNP concentrations between different gestational age has been reported (F=14.714, P=0.005), and the gestational age had significant negative correlation with the BNP concentration in normal fetuses (P=0.001; Spearman's r=-0.182)4 No significant correlation was observed between AF BNP values and fetal heart rate (P=0.293)[Conclusions] Our experiment established a normal values of amniotic fluid BNP concentration in healthy fetuses. Results confirm that there was significantly difference of AF BNP concentrations between different gestational age and the gestational age had significant negative correlation with the BNP concentration in normal fetuses. So we conclude that in any case, gestational age has to be taken into consideration in assessment of BNP concentrations of the fetuses.Chapter 2 Evaluation of fetal cardiac function by BNP and VVI and its application to congenital heart disease[Obejctives] To investigate the clinical value of evaluation of fetal cardiac function by BNP and VVI and its application to congenital heart disease[Methods] Group divided:The case group included fetuses who underwent systemic ultrasonic examination and amniocentesis and had been diagnosed congenital heart disease or combined with hydropericardium in Shenzhen maternity and child healthcare hospital from April 2010 to December 2010; The control group were healthy pregnant women without contributable history and the fetuses were the same as described in chapter one. All participating women gave their written consents. The methods of collecting AF and assaying BNP were the same as described in chapter one. Two-dimensional 4-chamber images of the heart were interrogated offline using Syngo US Workplace VVI software. Measurements of global and segmental longitudinal velocity, strain, strain rate were performed on the left ventricle. Statistical analyses were performed by the SPSS 13.0 software. Kolmogorov-Smirnov test (KS) revealed that BNP concentration of the case groups was Normal distribution. So the values for BNP are shown as Mean and standard deviation (SD). Comparison was made between the two groups and pearson correlation was used to analyse the BNP concentration and the fetal heart dynamic parameters and gestation age. P<0.05 was considered statistically significant.[Results]1,Comparison of amniotic fluid BNP between CHD and control group1 The expression and comparison of amniotic fluid BNP between CHD and control group:The amniotic fluid BNP concentrations in CHD group and control group was 1.523±1.133ng/ml and 1.141±0.665ng/ml respectively, There were significantly differences in amniotic fluid BNP concentrations between two groups (F=4.032, P=0.045).2 The gestational age had significant positive correlation with BNP concentrations in CHD group (r=0.289, P=0.049); The gestational age had significant negative correlation with BNP concentrations in normal fetus (r=-0.178, P=0.002). The fetal heart rate had no significant correlation with the BNP concentrations in CHD group and control group (P=0.492, P=0.293 respectively).3 The comparison of global velocity, strain and strain rate between CHD and control group in left ventricular showed significant differences (P=0.029; P=0.000; P=0.000, respectively). The mean value of left ventricular velocity, strain and strain rate in CHD group were (0.280±0.180 cm/s,-3.925±1.639%,-0.368±0.135/s); The mean value of left ventricular velocity, strain and strain rate in control group were (0.366±0.153 cm/s,-5.965±1.974%,-0.628±0.382/s). All of the left ventricular dynamic parameters in CHD group were lower than the normal group, the same as our preliminary experiment.4 The global velocity in left ventricular had significant negative correlation with the amniotic fluid BNP concentrations in control group (r=-0.347, P=0.012), however, the global dynamic parameters, such as velocity, strain and strain rate in left ventricular had no significant correlation with the amniotic fluid BNP concentrations in CHD group (P=0.977; P=0.975; P=0.387, respectively).[Conclusions]Compared with the normal control group, the CHD group had a high level of BNP in amniotic fluid and a lower level of dynamic parameters of left ventricular. There was a positive relationship between BNP concentration and gestational age in CHD group. The global dynamic parameters in left ventricular had no significant correlation with the amniotic fluid BNP concentration in CHD group, but the global velocity in left ventricular had significant negative correlation with the amniotic fluid BNP concentration in control group. So we concluded that BNP concentration could be an objective indicator for evaluation of fetal cardiac function, and had clinical values in CHD fetuses. Additionally, combined BNP concentration with VVI parameters could be a practical method to evaluate fetal cardiac function and monitor the progression of disease and clinical therapy.