Analysis of the uterine artery pulsatility index on the day of endometrial transformation and pregnancy outcomes of patients undergoing frozen-thawed embryo transfer.

Objective: The objective was to analyze the impact of the uterine artery pulsatility index (PI) on pregnancy outcomes by measuring uterine artery blood flow on the day of endometrial transformation in patients undergoing frozen-thawed embryo transfer (FET). Methods: This was a case-control study. In total, 2,036 patients who underwent FET at the Third Affiliated Hospital of Zhengzhou University from October 2019 to September 2020 were included. The patients were divided into a clinical pregnancy group and a nonclinical pregnancy group according to pregnancy outcome. A multivariate logistic regression model was used to analyze the factors affecting the clinical pregnancy rate. The receiver operating characteristic (ROC) curve was used to determine the optimal mean PI cutoff value of 1.75. After 1:1 propensity score matching (PSM), 562 patients were included. For statistical description and analysis, the patients were divided into two groups: a group with a mean PI > 1.75 and a group with a mean PI ≤ 1.75. Results: The clinical pregnancy group included 1,218 cycles, and the nonclinical pregnancy group included 818 cycles. There were significant differences in female age (P<0.01), infertility type (P=0.04), baseline follicle-stimulating hormone level (P=0.04), anti-Müllerian hormone (AMH) level (P<0.01), antral follicle count (P<0.01), number of transferred embryos (P=0.045) and type of transferred embryo (P<0.01). There was no significant difference in the mean bilateral PI (1.98 ± 0.34 vs. 1.95 ± 0.35, P=0.10). The multivariate analysis results showed that maternal age (AOR=0.95, 95% CI=0.93-0.98, P<0.01), AMH level (AOR=1.00, 95% CI=1.00-1.01, P=0.045), number of transferred embryos (AOR=1.98, 95% CI=1.47-2.70, P<0.01), and type of transferred embryo (AOR=3.10, 95% CI=2.27-4.23, P<0.01) were independent factors influencing the clinical pregnancy rate. The mean PI (AOR=0.85, 95% CI=0.70-1.05; P=0.13) was not an independent factor influencing the clinical pregnancy rate. Participants were divided into two groups according to the mean PI cutoff value of 1.75, and there was no significant difference between the two groups (P > 0.05). Conclusion: In this study, we found that the uterine artery PI on the day of endometrial transformation in patients undergoing FET is not a good predictor of pregnancy outcomes.

The role of second trimester uterine artery Doppler in predicting obstetric and neonatal outcomes in abnormal first trimester maternal serum pregnancy-associated plasma protein-A and free ß-human chorionic gonadotropin values.

AIM: This study aims to determine whether second-trimester uterine artery (UtA) Doppler combined with first-trimester abnormal pregnancy-associated plasma protein-A (PAPP-A) and ß-human chorionic gonadotropin (ß-Hcg) levels predicts adverse obstetric and neonatal outcomes. MATERIALS AND METHODS: This study of 289 pregnant women included 196 with normal PAPP-A and free ß-HCG values (control group) and 93 with abnormal values (study group) in the first-trimester screening test. Second-trimester UtA Doppler sonography was done in these pregnancies. The perinatal prediction and screening potential of UtA Doppler pulsatility index (PI) parameters were examined in the study group. RESULTS: UtA PI >95 percentile increased birth before the 37th week by 4.46 times, birth before the 34th week by 7.44 times, preeclampsia risk by 3.25 times, fetal growth restriction (FGR) risk by 4.89 times, and neonatal intensive care unit (NICU) admission rates by 3.66 times in the study group (p < 0.05 for all). UtA PI >95 percentile had 49.2% sensitivity and 82.1% specificity for birth before 37 weeks. For birth before 34 weeks, sensitivity was 80.0% and specificity 65.0%. FGR has 70.5% sensitivity and 67.1% specificity. Screening for preeclampsia has 66.6% sensitivity and 61.9% specificity. CONCLUSION: Adding UtA Doppler in the second trimester to pregnancies with abnormal PAPP-A and/or free ß-Hcg values in the first trimester may be a useful screening method for adverse outcomes.

Ophthalmic artery Doppler at 36 weeks' gestation in prediction of pre-eclampsia: validation and update of previous model.

OBJECTIVE: To validate and extend a model incorporating maternal ophthalmic artery Doppler at 35-37 weeks' gestation in the prediction of subsequent development of pre-eclampsia (PE). METHODS: This was a prospective validation study of screening for PE (defined according to the 2019 American College of Obstetricians and Gynecologists criteria) by maternal ophthalmic artery peak systolic velocity (PSV) ratio in 6746 singleton pregnancies undergoing routine care at 35 + 0 to 36 + 6 weeks' gestation (validation dataset). Additionally, the data from the validation dataset were combined with those of 2287 pregnancies that were previously used for development of the model (training dataset), and the combined data were used to update the original model parameters. The competing-risks model was used to estimate the individual patient-specific risk of delivery with PE at any time and within 3 weeks from assessment by a combination of maternal demographic characteristics and medical history with PSV ratio alone and in combination with the established PE biomarkers of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1). We evaluated the predictive performance of the model by examining, first, the ability to discriminate between the PE and non-PE groups using the area under the receiver-operating-characteristics curve and the detection rate (DR) at fixed screen-positive (SPR) and false-positive rates of 10% and, second, calibration by measuring the calibration slope and calibration-in-the-large. McNemar's test was used to compare the performance of screening by a biophysical test (maternal factors, MAP, UtA-PI and PSV ratio) vs a biochemical test (maternal factors, PlGF and sFlt-1), low PlGF concentration (< 10th percentile) or high sFlt-1/PlGF concentration ratio (> 90th percentile). RESULTS: In the validation dataset, the performance of screening by maternal factors and PSV ratio for delivery with PE within 3 weeks and at any time after assessment was consistent with that in the training dataset, and there was good agreement between the predicted and observed incidence of PE. In the combined data from the training and validation datasets, good prediction for PE was achieved in screening by a combination of maternal factors, MAP, UtA-PI, PlGF, sFlt-1 and PSV ratio, with a DR, at a 10% SPR, of 85.0% (95% CI, 76.5-91.4%) for delivery with PE within 3 weeks and 65.7% (95% CI, 59.2-71.7%) for delivery with PE at any time after assessment. The performance of a biophysical test was superior to that of screening by low PlGF concentration or high sFlt-1/PlGF concentration ratio but not significantly different from the performance of a biochemical test combining maternal factors with PlGF and sFlt-1 for both PE within 3 weeks and PE at any time after assessment. CONCLUSION: Maternal ophthalmic artery PSV ratio at 35-37 weeks' gestation in combination with other biomarkers provides effective prediction of subsequent development of PE. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Maternal vascular indices at 36 weeks' gestation in the prediction of preeclampsia.

BACKGROUND: Epidemiological studies have shown that women with preeclampsia (PE) are at increased long term cardiovascular risk. This risk might be associated with accelerated vascular ageing process but data on vascular abnormalities in women with PE are scarce. OBJECTIVE: This study aimed to identify the most discriminatory maternal vascular index in the prediction of PE at 35 to 37 weeks' gestation and to examine the performance of screening for PE by combinations of maternal risk factors and biophysical and biochemical markers at 35 to 37 weeks' gestation. STUDY DESIGN: This was a prospective observational nonintervention study in women attending a routine hospital visit at 35 0/7 to 36 6/7 weeks' gestation. The visit included recording of maternal demographic characteristics and medical history, vascular indices, and hemodynamic parameters obtained by a noninvasive operator-independent device (pulse wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressures, total peripheral resistance, and fetal heart rate), mean arterial pressure, uterine artery pulsatility index, and serum concentration of placental growth factor and soluble fms-like tyrosine kinase-1. The performance of screening for delivery with PE at any time and at <3 weeks from assessment using a combination of maternal risk factors and various combinations of biomarkers was determined. RESULTS: The study population consisted of 6746 women with singleton pregnancies, including 176 women (2.6%) who subsequently developed PE. There were 3 main findings. First, in women who developed PE, compared with those who did not, there were higher central systolic and diastolic blood pressures, pulse wave velocity, peripheral vascular resistance, and augmentation index. Second, the most discriminatory indices were systolic and diastolic blood pressures and pulse wave velocity, with poor prediction from the other indices. However, the performance of screening by a combination of maternal risk factors plus mean arterial pressure was at least as high as that of a combination of maternal risk factors plus central systolic and diastolic blood pressures; consequently, in screening for PE, pulse wave velocity, mean arterial pressure, uterine artery pulsatility index, placental growth factor, and soluble fms-like tyrosine kinase-1 were used. Third, in screening for both PE within 3 weeks and PE at any time from assessment, the detection rate at a false-positive rate of 10% of a biophysical test consisting of maternal risk factors plus mean arterial pressure, uterine artery pulsatility index, and pulse wave velocity (PE within 3 weeks: 85.2%; 95% confidence interval, 75.6%-92.1%; PE at any time: 69.9%; 95% confidence interval, 62.5%-76.6%) was not significantly different from a biochemical test using the competing risks model to combine maternal risk factors with placental growth factor and soluble fms-like tyrosine kinase-1 (PE within 3 weeks: 80.2%; 95% confidence interval, 69.9%-88.3%; PE at any time: 64.2%; 95% confidence interval, 56.6%-71.3%), and they were both superior to screening by low placental growth factor concentration (PE within 3 weeks: 53.1%; 95% confidence interval, 41.7%-64.3%; PE at any time: 44.3; 95% confidence interval, 36.8%-52.0%) or high soluble fms-like tyrosine kinase-1-to-placental growth factor concentration ratio (PE within 3 weeks: 65.4%; 95% confidence interval, 54.0%-75.7%; PE at any time: 53.4%; 95% confidence interval, 45.8%-60.9%). CONCLUSION: First, increased maternal arterial stiffness preceded the clinical onset of PE. Second, maternal pulse wave velocity at 35 to 37 weeks' gestation in combination with mean arterial pressure and uterine artery pulsatility index provided effective prediction of subsequent development of preeclampsia.

Screening for pre-eclampsia by maternal serum glycosylated fibronectin and angiogenic markers at 36 weeks' gestation.

OBJECTIVES: First, to examine the predictive performance of maternal serum glycosylated fibronectin (GlyFn) at 35 + 0 to 36 + 6 weeks' gestation in screening for delivery with pre-eclampsia (PE) and delivery with gestational hypertension (GH) at ≥ 37 weeks' gestation, both within 3 weeks and at any time after the examination. Second, to compare the predictive performance for delivery with PE and delivery with GH of various combinations of biomarkers, including GlyFn, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). Third, to compare the predictive performance for delivery with PE and delivery with GH by serum PlGF concentration, sFlt-1/PlGF concentration ratio and the competing-risks model with different combinations of biomarkers as above. Fourth, to compare the predictive performance of screening at 11 + 0 to 13 + 6 weeks vs 35 + 0 to 36 + 6 weeks for delivery with PE and delivery with GH at ≥ 37 weeks' gestation. METHODS: This was a case-control study in which maternal serum GlyFn was measured in stored samples from a non-intervention screening study in singleton pregnancies at 35 + 0 to 36 + 6 weeks' gestation using a point-of-care device. We used samples from women who delivered at ≥ 37 weeks' gestation, including 100 who developed PE, 100 who developed GH and 600 controls who did not develop PE or GH. In all cases, MAP, UtA-PI, PlGF and sFlt-1 were measured during the routine visit at 35 + 0 to 36 + 6 weeks. We used samples from patients that had been examined previously at 11 + 0 to 13 + 6 weeks' gestation. Levels of GlyFn were transformed to multiples of the expected median (MoM) values after adjusting for maternal demographic characteristics and elements from the medical history. Similarly, the measured values of MAP, UtA-PI, PlGF and sFlt-1 were converted to MoM. The competing-risks model was used to combine the prior distribution of the gestational age at delivery with PE, obtained from maternal risk factors, with various combinations of biomarker MoM values to derive the patient-specific risks of delivery with PE. The performance of screening of different strategies was estimated by examining the detection rate (DR) at a 10% fixed false-positive rate (FPR) and McNemar's test was used to compare the DRs between the different methods of screening. RESULTS: The DR, at 10% FPR, of screening by the triple test (maternal risk factors plus MAP, PlGF and sFlt-1) was 83.7% (95% CI, 70.3-92.7%) for delivery with PE within 3 weeks of screening and 80.0% (95% CI, 70.8-87.3%) for delivery with PE at any time after screening, and this performance was not improved by the addition of GlyFn. The performance of screening by a combination of maternal risk factors, MAP, PlGF and GlyFn was similar to that of the triple test, both for delivery with PE within 3 weeks and at any time after screening. The performance of screening by a combination of maternal risk factors, MAP, UtA-PI and GlyFn was similar to that of the triple test, and they were both superior to screening by low PlGF concentration (PE within 3 weeks: DR, 65.3% (95% CI, 50.4-78.3%); PE at any time: DR, 56.0% (95% CI, 45.7-65.9%)) or high sFlt-1/PlGF concentration ratio (PE within 3 weeks: DR, 73.5% (95% CI, 58.9-85.1%); PE at any time: DR, 63.0% (95% CI, 52.8-72.4%)). The predictive performance of screening at 35 + 0 to 36 + 6 weeks' gestation for delivery with PE and delivery with GH at ≥ 37 weeks' gestation was by far superior to screening at 11 + 0 to 13 + 6 weeks. CONCLUSION: GlyFn is a potentially useful biomarker in third-trimester screening for term PE and term GH, but the findings of this case-control study need to be validated by prospective screening studies. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Glycosylated fibronectin improves first-trimester prediction of pre-eclampsia.

OBJECTIVE: To determine whether maternal serum glycosylated fibronectin (GlyFn) level in the first trimester increases the sensitivity of the Fetal Medicine Foundation (FMF) triple test, which incorporates mean arterial pressure, uterine artery pulsatility index and placental growth factor, when screening for pre-eclampsia (PE) in an Asian population. METHODS: This was a nested case-control study of Chinese women with a singleton pregnancy who were screened for PE at 11-13 weeks' gestation as part of a non-intervention study between December 2016 and June 2018. GlyFn levels were measured retrospectively in archived serum from 1685 pregnancies, including 101 with PE, using an enzyme-linked immunosorbent assay (ELISA), and from 448 pregnancies, including 101 with PE, using a point-of-care (POC) device. Concordance between ELISA and POC tests was assessed using Lin's correlation coefficient and Passing-Bablok and Bland-Altman analyses. GlyFn was transformed into multiples of the median (MoM) to adjust for maternal and pregnancy characteristics. GlyFn MoM was compared between PE and non-PE pregnancies, and the association between GlyFn MoM and gestational age at delivery with PE was assessed. Risk for developing PE was estimated using the FMF competing-risks model. Screening performance for preterm and any-onset PE using different biomarker combinations was quantified by area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% fixed false-positive rate (FPR). Differences in AUC between biomarker combinations were compared using the DeLong test. RESULTS: The concordance correlation coefficient between ELISA and POC measurements was 0.86 (95% CI, 0.83-0.88). Passing-Bablok analysis indicated proportional bias (slope, 1.08 (95% CI, 1.04-1.14)), with POC GlyFn being significantly higher compared with ELISA GlyFn. ELISA GlyFn in non-PE pregnancies was independent of gestational age at screening (P = 0.11), but significantly dependent on maternal age (P < 0.003), weight (P < 0.0002), height (P = 0.001), parity (P < 0.02) and smoking status (P = 0.002). Compared with non-PE pregnancies, median GlyFn MoM using ELISA and POC testing was elevated significantly in those with preterm PE (1.23 vs 1.00; P < 0.0001 and 1.18 vs 1.00; P < 0.0001, respectively) and those with term PE (1.26 vs 1.00; P < 0.0001 and 1.22 vs 1.00; P < 0.0001, respectively). GlyFn MoM was not correlated with gestational age at delivery with PE (P = 0.989). Adding GlyFn to the FMF triple test for preterm PE increased significantly the AUC from 0.859 to 0.896 (P = 0.012) and increased the DR at 10% FPR from 64.9% (95% CI, 48.7-81.1%) to 82.9% (95% CI, 66.4-93.4%). The corresponding DRs at 10% FPR for any-onset PE were 52.5% (95% CI, 42.3-62.5%) and 65.4% (95% CI, 55.2-74.5%), respectively. CONCLUSIONS: Adding GlyFn to the FMF triple test increased the screening sensitivity for both preterm and any-onset PE in an Asian population. Prospective non-intervention studies are needed to confirm these initial findings. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Screening for pre-eclampsia by maternal serum glycosylated fibronectin at 11-13 weeks' gestation.

OBJECTIVE: To examine the performance of screening for preterm and term pre-eclampsia (PE) at 11-13 weeks' gestation by maternal factors and combinations of maternal serum glycosylated fibronectin (GlyFn), mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF). METHODS: This was a case-control study in which maternal serum GlyFn was measured using a point-of-care device in stored samples from a non-intervention screening study of singleton pregnancies at 11 + 0 to 13 + 6 weeks' gestation. In the same samples, PlGF was measured by time-resolved fluorometry. We used samples from women who delivered with PE at < 37 weeks' gestation (n = 100), PE at ≥ 37 weeks (n = 100), gestational hypertension (GH) at < 37 weeks (n = 100), GH at ≥ 37 weeks (n = 100) and 1000 normotensive controls with no pregnancy complications. In all cases, MAP and UtA-PI had been measured during the routine 11-13-week visit. Levels of GlyFn were transformed to multiples of the expected median (MoM) values after adjusting for maternal demographic characteristics and elements of medical history. Similarly, the measured values of MAP, UtA-PI and PlGF were converted to MoMs. The competing-risks model was used to combine the prior distribution of gestational age at delivery with PE, obtained from maternal characteristics, with various combinations of biomarker MoM values to derive the patient-specific risks of delivery with PE or GH at < 37 and ≥ 37 weeks' gestation. Screening performance was estimated by examining the area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at 10% fixed false-positive rate (FPR). RESULTS: The maternal characteristics and elements of medical history with a significant effect on the measurement of GlyFn were maternal age, weight, height, race, smoking status and history of PE. In pregnancies that developed PE, GlyFn MoM was increased and the deviation from normal decreased with increasing gestational age at delivery. The DR and AUC of screening for delivery with PE at < 37 weeks' gestation by maternal factors alone were 50% and 0.834, respectively, and these increased to 80% and 0.949, respectively, when maternal risk factors were combined with MAP, UtA-PI and PlGF (triple test). The performance of the triple test was similar to that of screening by a combination of maternal factors, MAP, UtA-PI and GlyFn (DR, 79%; AUC, 0.946) and that of screening by a combination of maternal factors, MAP, PlGF and GlyFn (DR, 81%; AUC, 0.932). The performance of screening for delivery with PE at ≥ 37 weeks' gestation was poor; the DR for screening by maternal factors alone was 35% and increased to only 39% with use of the triple test. Similar results were obtained when GlyFn replaced PlGF or UtA-PI in the triple test. The DR of screening for GH with delivery at < 37 and ≥ 37 weeks' gestation by maternal factors alone was 34% and 25%, respectively, and increased to 54% and 31%, respectively, with use of the triple test. Similar results were obtained when GlyFn replaced PlGF or UtA-PI in the triple test. CONCLUSIONS: GlyFn is a potentially useful biomarker in first-trimester screening for preterm PE, but the findings of this case-control study need to be validated by prospective screening studies. The performance of screening for term PE or GH at 11 + 0 to 13 + 6 weeks' gestation by any combination of biomarkers is poor. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Biomarkers at 6 weeks' gestation in the prediction of early miscarriage in pregnancy following assisted reproductive technology.

INTRODUCTION: Miscarriage is a major concern in early pregnancy among women having conceived with assisted reproductive treatments. This study aimed to examine potential miscarriage-related biophysical and biochemical markers at 6 weeks' gestation among women with confirmed clinical pregnancy following in vitro fertilization (IVF)/embryo transfer (ET) and evaluate the performance of a model combining maternal factors, biophysical and biochemical markers at 6 weeks' gestation in the prediction of first trimester miscarriage among singleton pregnancies following IVF/ET. MATERIAL AND METHODS: A prospective cohort study was conducted in a teaching hospital between December 2017 and January 2020 including women who conceived through IVF/ET. Maternal mean arterial pressure, ultrasound markers including mean gestational sac diameter, fetal heart activity, crown rump length and mean uterine artery pulsatility index (mUTPI) and biochemical biomarkers including maternal serum soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), kisspeptin and glycodelin-A were measured at 6 weeks' gestation. Logistic regression analysis was carried out to determine significant predictors of miscarriage prior to 13 weeks' gestation and performance of screening was estimated by receiver-operating characteristics curve analysis. RESULTS: Among 169 included pregnancies, 145 (85.8%) pregnancies progressed to beyond 13 weeks' gestation and had live births whereas 24 (14.2%) pregnancies resulted in a miscarriage during the first trimester. In the miscarriage group, compared to the live birth group, maternal age, body mass index, and mean arterial pressure were significantly increased; mean gestational sac diameter, crown rump length, mUTPI, serum sFlt-1, glycodelin-A, and the rate of positive fetal heart activity were significantly decreased, while no significant differences were detected in PlGF and kisspeptin. Significant prediction for miscarriage before 13 weeks' gestation was provided by maternal age, fetal heart activity, mUTPI, and serum glycodelin-A. The combination of maternal age, ultrasound (fetal heart activity and mUTPI), and biochemical (glycodelin-A) markers achieved the highest area under the curve (AUC: 0.918, 95% CI 0.866-0.955), with estimated detection rates of 54.2% and 70.8% for miscarriage before 13 weeks' gestation, at fixed false positive rates of 5% and 10%, respectively. CONCLUSIONS: A combination of maternal age, fetal heart activity, mUTPI, and serum glycodelin-A at 6 weeks' gestation could effectively identify IVF/ET pregnancies at risk of first trimester miscarriage.

One-dimensional analysis method of pulsatile blood flow in arterial network for REBOA operations.

Based on the generalized Darcy model, here we develop a linear one-dimensional (1D) composite model to predict the effects of the inserted balloon under REBOA operations on the dynamic characteristics of blood flow in flexible arterial networks. We first consider the effect of the decrease of cardiac output under different degrees of blood loss through employing the fourth-order lumped parameter model of cardiovascular system. Then, the effect of the inserted balloon is included by developing the relation between flow resistance and occlusion ratio with the neural network approach. Finally, the accuracy of the developed 1D composite model for REBOA operations, which can be solved analytically in the frequency domain, is verified by comparing to computational fluid dynamics (CFD) simulations. It is demonstrated that the 1D model is able to reproduce main features of the systemic circulation under balloon occlusion of the aorta during REBOA surgery. The 1D composite model could substantially reduce the computational time, which makes it possible to give the instant prediction of the working parameters during RABOA operations.

A handsewn pericardial valved pulmonary conduit: pulsatile flow loop in vitro and acute porcine in vivo evaluation.

OBJECTIVES: Right ventricle to pulmonary artery anatomic discontinuity is common in complex congenital heart malformations. Handsewn conduits are a practised method of repair. In a proof-of-concept study, we evaluated pulmonary valve replacement with a handsewn pericardial valved pulmonary conduit in vitro and in vivo. METHODS: A pulsatile flow-loop model (in vitro) and an acute 60-kg porcine model (in vivo) were used. With echocardiography and pressure catheters, baseline geometry and fluid dynamics were measured. The pulmonary valve was replaced with a handsewn glutaraldehyde-treated pericardial valved pulmonary conduit corresponding to a 21-mm prosthetic valve, after which geometric measurements and fluid dynamics were reassessed. RESULTS: In vitro, 15 pulmonary trunks at 4 l/min and 13 trunks at 7 l/min, and in vivo, 11 animals were investigated. The valved pulmonary conduit was straightforward to produce at the operating table and easy to suture in place. All valves were clinically sufficient in vitro and in vivo. The mean transvalvular pressure gradient in the native valve and the conduit was 8 mmHg [standard deviation (SD): 2] and 7 mmHg (SD: 2) at 4 l/min in vitro, 19 mmHg (SD: 3) and 17 mmHg (SD: 4) at 7 l/min in vitro and 3 mmHg (SD: 2) and 6 mmHg (SD: 3) in vivo. CONCLUSIONS: Our proof-of-concept demonstrates no early evidence of structural damage to the conduit, and the fluid dynamic data were acceptable. The handsewn conduit can be produced at the operating table.

[Surgical treatment of heart failure in China: towards the era of artificial heart].

The number of patients with heart failure in China is large, and the proportion of patients with end-stage heart failure continues to increase. The clinical effect of guideline-directed medications therapy for end-stage heart failure is poor. Heart transplantation is the most effective treatment for end-stage heart failure. But it is faced with many limitations such as the shortage of donors. In recent years, the research and development of artificial heart in China has made great progress. Three devices have been approved by the National Medical Products Administration for marketing, and another one is undergoing pre-marketing clinical trial. Since 2017, more than 200 cases of ventricular assist device implantation have been carried out in more than 34 hospitals in China. Among them, 70 patients in Fuwai Hospital, Chinese Academy of Medical Sciences had a 2-year survival rate of 90%. The first patient has survived more than 5 years with the device. More efforts should be put into the training of standardized technical team and quality control. Further research should be carried out in the aspects of pulsatile blood flow pump, fully implanted cable-free device, and improved biomaterial with better blood compatibility.

Comparison of hemodynamics and root configurations between remodeling and reimplantation methods for valve-sparing aortic root replacement: a pulsatile flow study.

PURPOSE: To compare the characteristics of reimplantation (RI) using grafts with sinuses and remodeling (RM) with/without external suture annuloplasty using a pulsatile flow simulator. METHODS: Porcine aortic roots were obtained from an abattoir, and six models of RM and RI with sinuses were prepared. External suture annuloplasty (ESA) was performed in the RM models to decrease the root diameter to 22 mm (RM-AP22) and 18 mm (RM-AP18). Valve models were tested at mean pulsatile flow and aortic pressure of 5.0 L/min and 120/80 (100) mmHg, respectively, at 70 beats/min. The forward flow, regurgitation, leakage, backflow rates, valve-closing time, and mean and peak pressure gradient (p-PG) were evaluated. Root configurations were examined using micro-computed tomography (micro-CT). RESULTS: The backflow rate was larger in the RM models than in the RI models (RI: 8.56% ± 0.38% vs. RM: 12.64% ± 0.79%; p < 0.01). The RM-AP and RI models were comparable in terms of the forward flow, regurgitation, backflow rates, p-PG, and valve-closing time. The analysis using a micro-CT showed a larger dilatation of the sinus of the Valsalva in the RM groups than in the RI group (Valsalva: RI, 26.55 ± 0.40 mm vs. RM-AP22, 31.22 ± 0.55 mm [p < 0.05]; RM-AP18, 31.05 ± 0.85 mm [p < 0.05]). CONCLUSIONS: RM with ESA and RI with neo-sinuses showed comparable hemodynamics. ESA to RM reduced regurgitation.

Efficacy of ultrasound vector flow imaging in tracking omnidirectional pulsatile flow.

BACKGROUND: Ultrasound vector flow imaging (VFI) shows potential as an emerging non-invasive modality for time-resolved flow mapping. However, its efficacy in tracking multidirectional pulsatile flow with temporal resolvability has not yet been systematically evaluated because of the lack of an appropriate test protocol. PURPOSE: We present the first systematic performance investigation of VFI in tracking pulsatile flow in a meticulously designed scenario with time-varying, omnidirectional flow fields (with flow angles from 0° to 360°). METHODS: Ultrasound VFI was performed on a three-loop spiral flow phantom (4 mm diameter; 5 mm pitch) that was configured to operate under pulsatile flow conditions (10 ml/s peak flow rate; 1 Hz pulse rate; carotid pulse shape). The spiral lumen geometry was designed to simulate recirculatory flow dynamics observed in the heart and in curvy blood vessel segments such as the carotid bulb. The imaging sequence was based on steered plane wave pulsing (-10°, 0°, +10° steering angles; 5 MHz imaging frequency; 3.3 kHz interleaved pulse repetition frequency). VFI's pulsatile flow estimation performance and its ability to detect secondary flow were comparatively assessed against flow fields derived from computational fluid dynamics (CFD) simulations that included consideration of fluid-structure interactions (FSI). The mean percentage error (MPE) and the coefficient of determination (R2 ) were computed to assess the correspondence of the velocity estimates derived from VFI and CFD-FSI simulations. In addition, VFI's efficacy in tracking pulse waves was analyzed with respect to pressure transducer measurements made at the phantom's inlet and outlet. RESULTS: Pulsatile flow patterns rendered by VFI agreed with the flow profiles computed from CFD-FSI simulations (average MPE: -5.3%). The shape of the VFI-measured velocity magnitude profile generally matched the inlet flow profile. High correlation exists between VFI measurements and simulated flow vectors (lateral velocity: R2  = 0.8; axial velocity R2  = 0.89; beam-flow angle: R2  = 0.98; p < 0.0001 for all three quantities). VFI was found to be capable of consistently tracking secondary flow. It also yielded pulse wave velocity (PWV) estimates (5.72 ± 1.02 m/s) that, on average, are within 6.4% of those obtained from pressure transducer measurements (6.11 ± 1.15 m/s). CONCLUSION: VFI can consistently track omnidirectional pulsatile flow on a time-resolved basis. This systematic investigation serves well as a quality assurance test of VFI.

A novel pulsatile blood pump design for cardiothoracic surgery: Proof-of-concept in a mock circulation.

BACKGROUND: Pulsatile perfusion during extracorporeal circulation is a promising concept to improve perfusion of critical organs. Clinical benefits are limited by the amount of pulsatile energy provided by standard pumps. The present study investigated the properties of a novel positive displacement blood pump in a mock circulation. METHODS: The pump was attached to an aortic model with a human-like geometry and compliance as a pseudo patient. Hemodynamic data were recorded while the pump settings were adjusted systematically. RESULTS: Using a regular oxygenator, maximum flow was 2.6 L/min at a pressure of 27 mm Hg and a frequency (F) of 90 bpm. Pulse pressure (PP; 28.9 mm Hg) and surplus hemodynamic energy (SHE; 26.1% of mean arterial pressure) were highest at F = 40 bpm. Flow and pressure profiles appeared sinusoid. Using a low-resistance membrane ventilator to assess the impact of back pressure, maximum flow was 4.0 L/min at a pressure of 58.6 mm Hg and F = 40 bpm. At F = 40 bpm, PP was 58.7 mm Hg with an SHE of 33.4%. SHE decreased with increasing flow, heart rate, and systolic percentage but surpassed 10% with reasonable settings. CONCLUSIONS: The present prototype achieved sufficient flow and pressure ranges only in the presence of a low-resistance membrane ventilator. It delivered supraphysiologic levels of pulse pressure and SHE. Further modifications are planned to establish this concept for adult pulsatile perfusion.

Improving adult pulsatile minimal invasive extracorporeal circulation in a mock circulation.

BACKGROUND: Pulsatile extracorporeal circulation (ECC) may improve perfusion of critical organs during cardiac surgery. This study analyzed the influence of the components of a minimal invasive ECC (MiECC) on the transfer of pulsatile energy into the pseudo-patient of a mock circulation. METHODS: An aortic model with human-like geometry and compliance was perfused by a diagonal pump. Surplus hemodynamic energy (SHE) was determined from flow and pressure data. Five adult-size oxygenator models and three sizes of cannulas were compared. Pulsatile pump settings were optimized, and parallel dual-pump configurations were evaluated. RESULTS: Oxygenator models showed up to twofold differences in pressure gradients and influenced SHE at flow rates up to 2.0 L min-1 . Adjustments of frequency, systole duration, and rotational speed gain significantly improved SHE compared with empirical settings, with SHE above 21% of mean arterial pressure at flow rates of 1.0 L min-1 to 1.5 L min-1 and SHE above 5% at 3.5 L min-1 . Small diameter cannula (15 Fr) limited SHE compared with larger cannula (21 Fr and 23 Fr). Two diagonal pumps did not provide higher SHE than a single pump, but permitted additional control over pulse pressure and SHE by varying the total fraction of pulsatile flow and the fraction of flow bypassing the oxygenator. CONCLUSIONS: Proper selection of components and optimizations of pump settings significantly improved pulse pressure and SHE of pulsatile MiECC. Surplus hemodynamic energy depended on flow rate with a maximum at 1.0 L min-1 -1.5 L min-1 . Pulsatile MiECC may specifically assist organ perfusion during phases of low flow.

Biocompatibility of the Oxygenator on Pulsatile Flow by Electron Microscope.

INTRODUCTION: Extracorporeal perfusion flow type requires further investigation. The aim of this study is to compare the effects of pulsatile and nonpulsatile flow on oxygenator fibers that were analyzed by scanning electron microscope (SEM) and to extensively study patients' coagulation profiles, inflammatory markers, and functional blood tests. METHODS: Twelve patients who had open heart surgery were randomly divided into two groups; the nonpulsatile flow (group NP, six patients) and pulsatile flow (group P, six patients) groups. Both superficial view and axial sections of the oxygenator fiber samples were examined under SEM to compare the thickness of absorbed blood proteins and amount of blood cells on the surface of oxygenators. Platelet count, coagulation profile, and inflammatory predictors were also studied from the blood samples. RESULTS: Fibrinogen levels after cardiopulmonary bypass were significantly lower in group NP (group P, 2.57±2.78 g/L; group NP; 2.39±0.70 g/L, P=0.03). Inflammatory biomarkers such as C-reactive protein, interleukin (IL)-6, IL-12, apelin, S100ß, and tumor necrosis factor alpha were comparable in both groups. Axial sections of the oxygenator fiber samples had a mean thickness of 45.2 µm and 46.5 µm in groups P and NP, respectively, and this difference is statistically significant (P=0.006). Superficial view of the fiber samples showed obviously lower platelet, leukocyte, and erythrocyte levels in group P. CONCLUSION: Our study demonstrated that both cellular elements and protein adsorption on oxygenator fibers are lower in the group P than in the group NP. Pulsatile perfusion has better biocompatibility on extracorporeal circulation when analyzed by SEM technique.

Pulsatile versus non-pulsatile perfusion in coronary artery bypass operation: The comparison of laboratory and clinical outcomes.

INTRODUCTION: The superiority of pulsatile or non-pulsatile perfusion in cardiopulmonary bypass (CPB) regarding morbidity and mortality is still debated. Therefore, we aimed to investigate the effect of different pulse rates in pulsatile perfusion in patients undergoing coronary artery bypass graft (CABG) and compared it with non-pulsatile perfusion. MATERIALS AND METHODS: In this randomized clinical trial, 90 patients who were all candidates for CABG under CPB were enrolled. Patients in groups A and B received pulsatile perfusion with 30 and 70 pulses per minute, and group C received non-pulsatile perfusion. The biochemical and clinical parameters in the ICU were evaluated in the study groups. RESULTS: There was no statistically significant difference between patients' clinical outcomes and kidney and liver function markers (all Ps> 0.05). Mean serum lactate level increased but did not show a statistically significant difference between the study groups (p = 0.8). The mean urine volume at 12 and 24 h after surgery was higher in group A, but there was no statistically significant difference between the three groups during the study period (p = 0.3). No significant difference was found in the length of the ICU stay between the study groups (p = 0.2). CONCLUSION: Our studied parameters demonstrated no significant difference between pulsatile and non-pulsatile and between 30 and 70 pulse rate pulsatile perfusion methods. Our findings support that pulsatile perfusion with different pulse rates has no advantages over non-pulsatile perfusion in selected CABG cases.

Hemodynamic analysis of hybrid treatment for thoracoabdominal aortic aneurysm based on Newtonian and non-Newtonian models in a patient-specific model.

The accuracy of the Newtonian model used in retrograde visceral revascularization (RVR) of hybrid surgery for thoracoabdominal aortic aneurysm (TAAA) hemodynamic simulation remains unclear. Noting that an appropriate blood viscosity model is a significant factor to capture hemodynamic changes in numerical studies. Therefore, both Newtonian and non-Newtonian blood viscosity models were adopted in this study to investigate the importance of hemodynamics when non-Newtonian blood property was accounted for in a patient-specific RVR simulation. The results revealed that disturbed flow and unfavorable WSS distribution can be observed in the anastomosis region under both blood viscosity models due to the retrograde flow pattern in the RVR model. However, although the non-Newtonian blood model has negligible effect on flow pattern and pressure drop, there were of significance quantitative and qualitative difference of local normalized helicity and wall shear stress distribution under pulsatile flow condition. In particular, the unfavorable WSS indicators distribution was better matched with a patient-specific follow-up report when non-Newtonian blood viscosity was accounted for. To conclude, the use of a Newtonian blood model is a reasonable approximation to obtain the general features of the flow field under steady flow condition. However, to study the hemodynamic parameters within retrograde flow under pulsatile flow condition, a non-Newtonian model may be more appropriate.

Pulsatile gas-liquid flow resembling Decompression Sickness: Computational Fluid Dynamics simulation and experimental validation.

BACKGROUND: This work performs two-dimensional Computational Fluid Dynamics (CFD) simulations of pulsatile bubbly flow in a column resembling the flow inside human vena cava during Decompression Sickness (DCS), aiming to illustrate the effect of certain parameters in bubbly blood flow and so facilitate the design of the: a) corresponding in-vitro bubbly flow experiments under pulsatile flow conditions inside a flow loop and b) in-vivo trials on swines for assessing a novel electrical impedance spectroscopy technique on the detection of bubbles (as those found during DCS) in their bloodstream. MATERIALS AND METHODS: The commercially available ANSYS 2019-R3 CFD code was employed to simulate the pulsatile bubbly flow that resembled DCS. Simulations were validated against experiments conducted in a vertical co-current upward pulsatile bubbly flow provided by a flow loop equipped with electrical, optical and pressure diagnostics. RESULTS: CFD simulations under pulsatile conditions were initially validated by oscillatory in-vitro bubbly flow experiments. Then, the influence of pulsation parameters on void fraction, α, and flow velocity, U, profiles was computationally investigated. Intense periodic fluctuations of void fraction were observed along the column and their intensity increases with pulsation amplitude. Moreover, U and α radial profiles were uniform for bubbles 30 µm but showed a core-peaking profile for bubbles 300 µm. CONCLUSIONS: CFD simulations of pulsatile bubbly flow resembling DCS provided unconventional information about the influence of different-sized sub-millimetre bubbles on the flow velocity and void fraction profiles, which are expected to improve the design of in-vitro and in-vivo trials for the detection of bubbles such as those found in DCS.

Pulsatile Perfusion during Cardiopulmonary Bypass: A Literature Review.

The use of cardiopulmonary bypass (CPB) in cardiac surgery has often been associated with postoperative organ dysfunction. Roller and centrifugal pumps produce non-pulsatile flow (NPF) by default, and this still is the most widely used mode of perfusion. The development of pulsatile pumps has allowed comparisons to be made with NPF. Pulsatile flow (PF) mimics the arterial pulse generated by the heart and is thought to be more physiological by some. This review aims to examine the proposed mechanisms behind the potential physiological benefits of PF during CPB and to summarize the current clinical evidence. MEDLINE and EMBASE were used to identify articles published over a 25 year period from 1995 to 2020. A literature review was conducted to determine the effects of PF on organ functions. A total of 44 articles were considered. Most of the articles published on PF were randomized controlled trials (RCTs). However, there was a wide variation in study methodology, method of pulse generation and how pulsatility was measured. Most of the evidence in favor of PF showed a marginal improvement on renal and pulmonary outcomes. In these studies, pulsatility was generated by an intra-aortic balloon pump. In conclusion, there is a lack of good quality RCTs that can inform on the short- and long-term clinical outcomes of PF. Further research is required in order to draw a conclusion with regards to the benefits of PF on organ function.