The alterations of cardiac function during venovenous artificial placenta support in fetal goats.

INTRODUCTION: Venovenous artificial placenta (VVAP) may mimic the intrauterine environment for maintaining fetal circulation. However, changes in ventricular function in fetal goats undergoing VVAP support remain unclear. METHODS: Pump-assisted VVAPs were established in five fetal goats for 9 h. The myocardial performance index (Tei index), cardiac output (CO), and blood biochemical parameters were measured during VVAP support. RESULTS: An increasing trend of the right ventricular (RV) Tei index was seen during VVAP support (p for trend < 0.01). The right ventricular cardiac output (RVCO) increased after the initiation of VVAP, while a significant trend of reduction was observed after 3 h (p for trend = 0.03). During VVAP support, we observed remarkable elevations of plasma cTnI and arterial lactic acid, which were positively correlated with the RV Tei index, but not the left ventricular (LV) Tei index, LVCO, and RVCO. CONCLUSIONS: The RVCO increases initially while a tendency of decrease could be observed during VVAP support. Special attention should be paid to right ventricular dysfunction during VVAP support.

Echocardiographic characteristics and clinical outcomes in fetuses with pulmonary stenosis or pulmonary atresia with intact ventricular septum.

OBJECTIVE: To summarize echocardiographic characteristics of the anatomy and hemodynamic and clinical outcomes in fetuses with isolated pulmonary stenosis (PS) or pulmonary atresia with intact ventricular septum (PA/IVS). METHODS: This was a single-center retrospective study of fetuses with isolated PS or PA/IVS. Echocardiographic variables and clinical outcomes after delivery were evaluated and compared. RESULTS: Between 2016 and 2021, 115 livebirths with isolated PS or PA/IVS were included. Proportion of fetuses with mild, moderate and critical PS and PA/IVS was 41.7 %, 18.3 %, 26.1 % and 13.9 %. Fetuses with more severe PS had worse anatomic and hemodynamic profiles. Specifically, the cardiothoracic ratio, pulmonary valve (PV) velocity, degree and velocity of tricuspid regurgitation increased as PS severity increased; and the pulmonary artery/aorta ratio, right ventricle/left ventricle long-axis (TV/MV) ratio, tricuspid valve/mitral valve annulus (TV/MV) ratio, and tricuspid valve inflow duration/cardiac cycle ratio decreased as PS severity increased (P <0.001 for all). PV velocity ≥2 m/s predicted PV pressure ≥40 mm Hg after delivery, with an AUC of 0.81; TV/MV ratio combined with RV/LV ratio predicted clinical outcomes, with an AUC of 0.88. Live births with more severe PS had higher mortality rate (mild 0 vs. moderate 0 vs. critical 11 % vs. PA-IVS 36 %) and lower rate of developing bi-ventricles (mild 100 % vs. moderate 95 % vs. critical 89 % vs. PA-IVS 36 %). CONCLUSION: Findings of this study help better understand the anatomy and hemodynamic and clinical outcomes in fetuses with isolated PS or PA/IVS, which could have implications for prenatal counseling and prediction of fetal outcome.

A multicenter study on two-stage transfer learning model for duct-dependent CHDs screening in fetal echocardiography.

Duct-dependent congenital heart diseases (CHDs) are a serious form of CHD with a low detection rate, especially in underdeveloped countries and areas. Although existing studies have developed models for fetal heart structure identification, there is a lack of comprehensive evaluation of the long axis of the aorta. In this study, a total of 6698 images and 48 videos are collected to develop and test a two-stage deep transfer learning model named DDCHD-DenseNet for screening critical duct-dependent CHDs. The model achieves a sensitivity of 0.973, 0.843, 0.769, and 0.759, and a specificity of 0.985, 0.967, 0.956, and 0.759, respectively, on the four multicenter test sets. It is expected to be employed as a potential automatic screening tool for hierarchical care and computer-aided diagnosis. Our two-stage strategy effectively improves the robustness of the model and can be extended to screen for other fetal heart development defects.

Machine learning model for predicting 1-year and 3-year all-cause mortality in ischemic heart failure patients.

OBJECTIVE: Machine learning (ML) model has not been developed specifically for ischemic heart failure (HF) patients. Whether the performance of ML model is better than the MAGGIC risk score and NT-proBNP is unknown. The current study was to apply ML algorithm to build risk model for predicting 1-year and 3-year all-cause mortality in ischemic HF patient and to compare the performance of ML model with the MAGGIC risk score and NT-proBNP. METHOD: Three ML algorithms without and with feature selection were used for model exploration, and the performance was determined based on the area under the curve (AUC) in five-fold cross-validation. The best performing ML model was selected and compared with the MAGGIC risk score and NT-proBNP. The calibration of ML model was assessed by the Brier score. RESULTS: Random forest with feature selection had the highest AUC (0.742 and 95% CI: 0.697-0.787) for predicting 1-year all-cause mortality, and support vector machine without feature selection had the highest AUC (0.732 and 95% CI: 0.694-0.707) for predicting 3-year all-cause mortality. When compared to the MAGGIC risk score and NT-proBNP, ML model had a comparable AUC for predicting 1-year (0.742 vs 0.714 vs 0.694) and 3-year all-cause mortality (0.732 vs 0.712 vs 0.682). Brier scores for predicting 1-year and 3-year all-cause mortality were 0.068 and 0.174, respectively. CONCLUSION: ML models predicted prognosis in ischemic HF with good discrimination and well calibration. These models may be used by clinicians as a decision-making tool to estimate the prognosis of ischemic HF patients.

Pharmacokinetics and pharmacodynamics of sildenafil in fetal lambs on extracorporeal support.

BACKGROUND: Maternal transplacental administration of sildenafil is being considered for a variety of fetal conditions. Clinical translation also requires evaluation of fetal safety in a higher species, such as the fetal lamb. Experiments with the pregnant ewe are curtailed by minimal transplacental transfer as well as limited access to the fetus. The EXTra-uterine Environment for Neonatal Development (EXTEND) model renders the isolated fetal lamb readily accessible and allows for direct fetal administration of sildenafil. METHODS: Five fetal lambs were placed on extracorporeal support in the EXTEND device and received continuous intravenous (IV) sildenafil (0.3-0.5-0.7 mg/kg/24hr) for a duration of one to seven days. Plasma sildenafil concentrations were sampled at regular intervals to establish the pharmacokinetic profile using population pharmacokinetic modeling. Serial Doppler ultrasound examination, continuous non-invasive hemodynamic monitoring and blood gas analysis were done to evaluate the pharmacodynamic effects and fetal response. FINDINGS: The target concentration range (47-500 ng/mL) was attained with all doses. Sildenafil induced an immediate and temporary reduction of pulmonary vascular resistance, mean arterial pressure and circuit flow, without change in fetal lactate levels and acid-base status. The duration of the systemic effects increased with the dose. INTERPRETATION: Immediate temporary pulmonary vascular and systemic hemodynamic changes induced by sildenafil were biochemically well tolerated by fetal lambs on extracorporeal support, with the 0.5 mg/kg/24 h dose balancing rapid attainment of target concentrations with short-lived systemic effects. RESEARCH IN CONTEXT: None. SEARCH STRATEGY BEFORE UNDERTAKING THE STUDY: A literature review was conducted searching online databases (Medline, Embase and Cochrane), using search terms: fetal OR prenatal OR antenatal AND sildenafil, without time-limit and excluding human studies. Where relevant, investigators were contacted in order to avoid duplication of work. EVIDENCE BEFORE THIS STUDY: Prenatal therapy with sildenafil, a phosphodiesterase-5 inhibitor with vasodilatory and anti-remodeling effects on vascular smooth muscle cells, has been considered for a variety of fetal conditions. One multicenter clinical trial investigating the benefit of sildenafil in severe intrauterine growth restriction (the STRIDER-trial) was halted early due to excess mortality in the sildenafil-exposed arm at one treatment site. Such findings demonstrate the importance of extensive preclinical safety assessment in relevant animal models. Transplacentally administered sildenafil leads to decreased pulmonary arterial muscularization, preventing or reducing the occurrence of pulmonary hypertension in rat and rabbit fetuses with diaphragmatic hernia (DH). Validation of these results in a higher and relevant animal model, e.g. fetal lambs, is the next step to advance clinical translation. We recently demonstrated that, in contrast to humans, transplacental transfer of sildenafil in sheep is minimal, precluding the in vivo study of fetal effects at target concentrations using the conventional pregnant ewe model. ADDED VALUE OF THIS STUDY: We therefore used the extracorporeal support model for fetal lambs, referred to as the EXTra-uterine Environment for Neonatal Development (EXTEND) system, bypassing placental and maternal metabolism, to investigate at what dose the target concentrations are reached, and what the fetal hemodynamic impact and response are. Fetal hemodynamic and metabolic tolerance to sildenafil are a crucial missing element on the road to clinical translation. This is therefore the first study investigating the pharmacokinetics, hemodynamic and biochemical effects of clinical-range concentrations of sildenafil in fetal lambs, free from placental and maternal interference. IMPLICATIONS OF ALL THE AVAILABLE EVIDENCE: We demonstrated self-limiting pulmonary vasodilation, a decrease of both systemic arterial pressures and circuit flows, induced by clinical range concentrations of sildenafil, without the development of fetal acidosis. This paves the way for further investigation of prenatal sildenafil in fetal lambs on extracorporeal support. A dose of 0.5 mg/kg/24 h offered the best trade-off between rapid achievement of target concentrations and shortest duration of systemic effects. This is also the first study using the EXTEND as a model for pharmacotherapy during pregnancy.

Fetal Pulmonary Valvuloplasty in Fetuses with Right Ventricular Outflow Tract Obstructive Disease: Experience and Outcome of the First Five Cases in China.

The current study was to report our initial experiences of fetal pulmonary valvuloplasty (FPV) for fetuses with pulmonary atresia with intact ventricular septum (PA/IVS) and critical pulmonary stenosis (CPS), including case selection, technical feasibility, and the effects of FPV on utero and postnatal outcome. Two fetuses with PA/IVS and three fetuses with CPS were enrolled between September 2016 and April 2018. All fetuses were with concomitant severe right ventricular dysplasia and growth arrest. Parameters of right cardiac development and hemodynamics, including tricuspid/mitral annulus ratio (TV/MV), right ventricle/left ventricle long-axis ratio (RV/LV), tricuspid valve inflow duration/cardiac cycle ratio (TVI/CC), degree of tricuspid regurgitation (TR), and blood flow direction of arterial duct and ductus venosus, were evaluated using echocardiogram. FPV was performed trans-abdominally under ultrasound guidance. Echocardiogram was performed post-FPV and every 2-4 weeks thereafter until delivery. The median gestational age at the time of FPV was 28 weeks. From technical perspective, pulmonary balloon valvuloplasty was successfully performed and the opening of pulmonary valve was improved in all fetuses in 2-4 weeks. However, progressive restenosis was observed in four fetuses with gestation advancing, and re-atresia occurred in two PA/IVS fetuses at 36th and 37th weeks' gestation, respectively. The growth trajectories of TV/MV, RV/LV, and TVI/CC were improved in the 1st week after FPV and then slowed down along with pulmonary valve restenosis. All fetuses were born alive and underwent postnatal interventions, including pulmonary balloon valvuloplasty in three fetuses and surgical procedures in two fetuses. During follow-up, three fetuses turned to be biventricular, one became one and a half ventricular at 1-year old, and one died of neonatal infection. Although pulmonary valve restenosis might occur as gestation advancing, FPV seems to be a safe and feasible procedure to improve the growth trajectories of right heart for fetuses with PA/IVS and CPS.

Congenital coronary artery fistula in pediatric patients: transcatheter versus surgical closure.

OBJECTIVES: Transcatheter closure (TCC) and surgical closure (SC) are the two main approaches for congenital coronary artery fistula (CCAF), but data on the comparisons of the efficacy and safety of these two approaches are limited. METHODS: We retrospectively reviewed pediatric patients with CCAF in Guangdong Cardiovascular Institute between January 2002 and December 2017. Patients who were qualified into our criteria were included into final analysis. The rate of successful closure and complications during hospitalization and at follow-up were compared between SC and TCC groups. RESULTS: In total, 121 pediatric patients (male, n = 69; female, n = 52) with CCAF were divided to TCC (n = 63) and SC groups (n = 58) according to the indications. The mean age was 5.3 ± 1.4 years. The baseline characteristics of these two groups were similar except for the fistula anatomic feature. After adjusted for the fistula anatomy, compared to SC, TCC was associated with higher risk of major complications (p = 0.013). Proportions of patients requiring blood transfusion and intra-operative blood loss were higher in SC versus TCC groups, as were longer duration of hospital and ICU stay during hospitalization. In contrast, myocardial ischemia (10.2% vs 0.0%, p = 0.028), residual shunts (16.9% vs 3.6%, p = 0.045) and new-onset moderate-to-severe valve regurgitation (11.9% vs 0.0%, p = 0.013) were higher in TCC group versus SC groups during follow-up. CONCLUSIONS: TCC has less invasive and faster recovery. However, SC had a higher successful rate and lower risk of major complications in pediatric patients.

[Anomalous origin of the left coronary artery from the pulmonary artery in infants: clinical features and the perioperative treatment strategies].

OBJECTIVE: To investigate the clinical features and individualized treatment strategies for infants with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). METHOD: Data of 25 less than 1-year-old infants with ALCAPA who presented at Guangdong Cardiovascular Institute between 2006 and 2013 were retrospectively reviewed. The patients' cardiac function was evaluated with echocardiography during follow-up. RESULT: Most patients presented with symptoms of heart failure, such as tachypnea, diaphoresis, poor feeding, failure to thrive etc. Electrocardiogram showed abnormal q wave in 23 patients and ST-T segment change in 16 patients.Echocardiography showed dilated left ventricle in 25 patients, endocardial hyperplasia in 5 patients, dilated right coronary artery and extensive collateralization between the right and left coronary artery systems in 11 patients. The left ventricular ejection fraction (LVEF) was (45.5±13.9)% (25%-77%). The left ventricular fractional shortening (LVFS) was (22.0±7.3)% (12%-38%). Twenty one patients underwent cardiovascular CT scan. Left coronary artery originated from left posterior sinus in 9 patients, from right posterior sinus in 1 patient, from lower main pulmonary artery in 5 patients, from the bifurcation of main pulmonary artery in 1 patient.Five patients showed ambiguous left coronary artery origination.Sixteen patients were misdiagnosed in other primary or secondary hospitals in 17 patients who were transferred to our tertiary hospital, only 1 case who underwent angiography was diagnosed correctly. Two patients were misdiagnosed in 8 patients first-presented in our hospital. Their diagnoses were corrected after reexamining with echocardiography and cardiovascular CT scan. The preoperative therapies included using inotropic agents, diuretics and vasodilators according to cardiac function. Two patients underwent left coronary artery orifice ligation. Twenty three patients underwent reimplantation of left coronary artery to reconstruct dual coronary system. Patients of NYHA IV with moderate mitral regurgitation (MR) and NYHA III with severe MR underwent mitral annuloplasty. If LVEF was less than 30% after weaning from cardiopulmonary bypass, blood pressure could not be maintained with medication, or lactates increased progressively, extracorporeal membrane oxygenation (ECMO) was demanded. Two patients showed low cardiac output syndrome immediately after surgical procedures, died from refractory ventricular fibrillation even with ECMO.In survived 23 patients during the early stage after surgeries, duration of ventilation was 7-500 hours, 11 of them were supported with ventilator for less than 60 hours. The mean length of hospital stay was (23.4±13.9) d (8-65 d). The follow-up duration ranged from 1-91 months (median 28.5 months). One case was lost to follow up. The patient died from infection 3 months after discharge. The cardiac functions of the remaining 22 patients were improved. The size of left ventricle of 14 patients recovered to normal. LVEF increased to the normal level in 20 cases. No patient underwent redo procedure. CONCLUSION: The accurate diagnosis can be made based on history, electrocardiogram, echocardiography and other imaging diagnostic tools.Individualized treatment strategy is helpful for seriously sick infants. Aggressive ECMO support can increase surviving rate for patients with postoperative low cardiac output syndrome.

[Clinical study of neonatal cardiac output measurement methods].

OBJECTIVE: To assess agreement between the ultrasonic cardiac output monitor (USCOM) and conventional echocardiography (ECHO) in the measurement of cardiac output in newborn infants, investigate the accuracy and clinical utility of the USCOM in healthy neonates. To explore a more convenient, faster, more accurate hemodynamic monitoring method, for improving the outcome of the critically ill neonates. METHOD: From October 1(st), 2011 to March 31(st), 2012, a total of 49 infants were included, 20 were term infants, 29 were preterm infants. Cardiac outputs were measured by both ultrasonic cardiac output monitor and echocardiography in all the infants, 60 times measurements were done in both the term infants the preterm infants. The cardiac output of the left and right ventricles, heart rate, diameter and velocity time integral of the aortic valve and pulmonary artery valve of each infant were recorded. The consistency of two methods was analyzed as described by Bland-Altman. RESULT: Term the term infant group includea 20 term infants, 11 were male and 9 were female, the mean gestational age were (38.1 ± 0.56) weeks, mean age were (2 ± 1) days, mean weight were (3.2 ± 0.29) kg, mean Apgar score were 10. The mean left ventricular output measured by Echo was (242.3 ± 38.9) ml/(kg·min), measured by USCOM was (211.7 ± 38.5) ml/(kg·min); The mean right ventricular output measured by ECHO was (318.9 ± 47.0) ml/(kg·min), measured by USCOM was (340.7 ± 76) ml/(kg·min). Agreement between Echo and USCOM for left ventricular output (LVO) was (bias, ± limits of agreement, mean % error): (30.6 ± 51.1) ml/(kg·min), 21%, and for right ventricular output (RVO): (-21.8 ± 105) ml/(kg·min), 33.2%. The diameter of the aortic valve and pulmonary artery valve measured by conventional echocardiography were significantly larger than that estimated by ultrasonic cardiac output monitor (P < 0.001). The velocity time integral of the pulmonary artery valve measured by ultrasonic cardiac output monitor were significantly larger than measured by conventional echocardiography (P < 0.001). The heart rate, velocity time integral of the aortic valve measured by two methods had no significant differences (P > 0.05). The preterm neonates group included 29 preterm infants, 18 were male and 11 were female, the mean gestational age were (32.6 ± 2.8) weeks, mean age were (2 ± 1) days, mean weight were (1.88 ± 0.57) kg. All the infants were diagnosis as preterm infant, low birth weight. The mean left ventricular output measured by ECHO was (259.8 ± 70) ml/(kg·min), measured by USCOM was (235.6 ± 61.8) ml/(kg·min), the mean right ventricular output measured by ECHO was (318.9 ± 47.0) ml/(kg·min), measured by USCOM was (340.7 ± 76) ml/(kg·min). Agreement between Echo and USCOM for left ventricular output (LVO) was (bias, ± limits of agreement, mean % error): (24.1 ± 71.2) ml/(kg·min), 27.4%, and for right ventricular output (RVO): (-29.5 ± 192.9) ml/(kg·min), 51.8%. The diameter of the aortic valve and pulmonary artery valve measured by conventional echocardiography were significantly larger than estimated by ultrasonic cardiac output monitor (P < 0.001). The velocity time integral of the pulmonary artery valve measured by USCOM were significantly larger than that measured by conventional echocardiography (P < 0.001). The heart rate, velocity time integral of the aortic valve measured by two methods had no significant differences (P > 0.05). CONCLUSION: Agreement between USCOM and conventional ECHO in the LVO measurement is acceptable, both in the term group and the preterm group. LVO measurement measured by USCOM is recommended. The accuracy and clinical utility of the USCOM in neonates is acceptable. USCOM is a convenient, fast and accurate hemodynamic monitoring method in neonates. While the agreement between USCOM and conventional ECHO in the RVO measurement is poor, especially in the preterm group, the results of the RVO cannot be considered interchangeable in the two methods.