Transcatheter Patent Ductus Arteriosus Closure in Premature Infants: Comparison of Echocardiogram and Angiogram Measurements.

Transcatheter patent ductus arteriosus (PDA) closure (TCPC) utilizing transthoracic echocardiogram (TTE) as the sole imaging guide could simplify care. This single-center study compares PDA dimensions obtained from the TTE and angiogram images of patients who underwent attempted TCPC at Stead Family Children's Hospital from 10/01/2019 to 10/31/2020. Blinded investigators measured these dimensions solely for this study and had no impact on clinical care. Also, a hypothetical Piccolo device size was chosen based on the TTE dimensions and another on the angiographic dimensions, and then the correlation was analyzed. Sixty-two patients underwent TCPC attempts. TTE tends to overestimate the PDA narrowest dimension and underestimate the PDA length and aortic end dimension. Linear regression analysis revealed a weak correlation between the length and aortic diameter (R = 0.37 and 0.21, respectively). A modest correlation was observed for the smallest dimension without color Doppler (R = 0.57) and with color Doppler, which was utilized when needed (R = 0.6). Bland-Altman analysis revealed a smaller mean difference between the TTE and angiogram measurements of the narrowest diameter without color Doppler (0.4 mm) and with color Doppler (used as needed) (0.4 mm). However, the mean difference is larger for the aortic end (- 1.64 mm) and the length (- 1.73 mm). TTE accurately predicted the Piccolo device size in 43 (72%) patients and overestimated the size in 17 (28%) patients to the next size. Our findings should be verified with further studies, and additional development of protocols is needed to use TTE to guide TCPC without fluoroscopy.

A recommendation for the use of electrical biosensing technology in neonatology.

Non-invasive cardiac output monitoring, via electrical biosensing technology (EBT), provides continuous, multi-parameter hemodynamic variable monitoring which may allow for timely identification of hemodynamic instability in some neonates, providing an opportunity for early intervention that may improve neonatal outcomes. EBT encompasses thoracic (TEBT) and whole body (WBEBT) methods. Despite the lack of relative accuracy of these technologies, as compared to transthoracic echocardiography, the use of these technologies in neonatology, both in the research and clinical arena, have increased dramatically over the last 30 years. The European Society of Pediatric Research Special Interest Group in Non-Invasive Cardiac Output Monitoring, a group of experienced neonatologists in the field of EBT, deemed it appropriate to provide recommendations for the use of TEBT and WBEBT in the field of neonatology. Although TEBT is not an accurate determinant of cardiac output or stroke volume, it may be useful for monitoring longitudinal changes of hemodynamic parameters. Few recommendations can be made for the use of TEBT in common neonatal clinical conditions. It is recommended not to use WBEBT to monitor cardiac output. The differences in technologies, study methodologies and data reporting should be addressed in ongoing research prior to introducing EBT into routine practice. IMPACT STATEMENT: TEBT is not recommended as an accurate determinant of cardiac output (CO) (or stroke volume (SV)). TEBT may be useful for monitoring longitudinal changes from baseline of hemodynamic parameters on an individual patient basis. TEBT-derived thoracic fluid content (TFC) longitudinal changes from baseline may be useful in monitoring progress in respiratory disorders and circulatory conditions affecting intrathoracic fluid volume. Currently there is insufficient evidence to make any recommendations regarding the use of WBEBT for CO monitoring in neonates. Further research is required in all areas prior to the implementation of these monitors into routine clinical practice.

Procedural closure of the patent ductus arteriosus in preterm infants: a clinical practice guideline.

IMPORTANCE: Transcatheter closure of the patent ductus arteriosus (PDA) is being increasingly adopted as an alternative to surgical PDA closure in preterm infants. OBJECTIVE: To develop rigorous clinical practice guideline recommendations on procedural PDA closure in preterm infants. METHODS: The principles of the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence-to-Decision (EtD) framework were used to develop the guideline recommendations. An e-Delphi survey of 45 experts was conducted and recommendations that reached ≥75% agreement were accepted as consensus. MAIN RECOMMENDATIONS: Procedural PDA closure may be considered in extremely preterm infants (<28 weeks gestational age) requiring invasive mechanical ventilation >10 postnatal days and confirmed to have a large hemodynamically significant PDA, at centers with high local rates of death and/or bronchopulmonary dysplasia (conditional recommendation). If sufficient institutional expertise is available and patient characteristics are suitable, transcatheter PDA closure may be considered as the preferred approach over PDA ligation (conditional recommendation).

Echocardiographic evaluation of left atrial volume and comparative analysis to left atrial to aortic root ratio in premature neonates and infants with patent ductus arteriosus.

PURPOSE: Left atrium to aortic root ratio (LA/Ao) is an echocardiographic marker of hemodynamically significant patent ductus arteriosus (PDA). Since 2-dimensional measurement of the ratio is geometrically limited, left atrial volume (LAV) which has 3-dimensional characteristics was investigated. The aim of this study was to determine a correlation between LA/Ao ratio and LAV as well as holodiastolic flow reversal in preterm neonates with and without a PDA. METHODS: A retrospective evaluation of neonates with and without PDA was performed. Targeted neonatal echocardiography evaluation of LA/Ao and LAV was measured from parasternal long-axis view and the apical 4 and 2-chamber views, respectively. Univariate and linear regression analysis were performed. RESULTS: 200 patients were included of whom 158 (79.0%) had a PDA shunt. The median gestational age at the time of echo was 27.4 weeks (IQR: 25.7-29.4 weeks). The median LA/Ao ratio was 1.51 (IQR: 1.26-1.83) and median LAV indexed to weight was  .91 mL/kg (IQR: .65-1.18 mL/kg). There was a significant correlation between LA/Ao and LAV indexed to weight in the PDA group (r2 = .080, p = .0003). LA/Ao ratio and LAV indexed to weight differed significantly between those with diastolic flow reversal versus no-flow reversal (LA/Ao, p = .003; LAV, p = .001). CONCLUSIONS: This study demonstrated a significant correlation between LA/Ao and LAV in preterm infants with PDA, with greater magnitude of discordance for LAV. The power of LAV versus LA/Ao in monitoring hemodynamically significant PDA requires prospective evaluation.

Selective early medical treatment of the patent ductus arteriosus in extremely low gestational age infants: a pilot randomised controlled trial protocol (SMART-PDA).

INTRODUCTION: Patent ductus arteriosus (PDA) is the most common cardiovascular problem that develops in extremely preterm infants and is associated with poor clinical outcomes. Uncertainty exists on whether early pharmacotherapeutic treatment of a clinically symptomatic and echocardiography-confirmed haemodynamically significant PDA in extremely preterm infants improves outcomes. Given the wide variation in the approach to PDA treatment in this gestational age (GA) group, a randomised trial design is essential to address the question. Before embarking on a large RCT in this vulnerable population, it is important to establish the feasibility of such a trial. METHODS AND ANALYSIS: Design: a multi-centre, open-labelled, parallel-designed pilot randomised controlled trial. Participants: preterm infants born <26 weeks of gestation with a PDA diagnosed within 72 hours after birth. Intervention (selective early medical treatment (SMART) strategy): selective early pharmacological treatment of a moderate-severe PDA shunt (identified based on pre-defined clinical signs and routine screening echocardiography) within the first 72 postnatal hours with provision for repeat treatment if moderate-severe shunt persists. Comparison (early conservative management strategy): no treatment of PDA in the first postnatal week. Primary outcomes: (1) proportion of eligible infants recruited during the study period; (2) proportion of randomised infants treated outside of protocol-mandated therapy. Sites and sample size: the study is being conducted in seven neonatal intensive care units across Canada and the USA with a target of 100 randomised infants. Analysis: the primary feasibility outcomes will be expressed as proportions. A pre-planned Bayesian analysis will be conducted for secondary clinical outcomes such as mortality, severe intraventricular haemorrhage, procedural PDA closure and chronic lung disease to aid stakeholders including parent representatives decide on the appropriateness of enrolling this vulnerable population in a larger trial if the feasibility of recruitment in the pilot trial is established. ETHICS AND DISSEMINATION: The study has been approved by the IWK Research Ethics Board (#1027298) and six additional participating sites. On the completion of the study, results will be presented at national and international meetings, published in peer-reviewed journals and incorporated into existing systematic reviews. TRIAL REGISTRATION NUMBER: NCT05011149 (WHO Trial Registration Data Set in Appendix A). PROTOCOL VERSION: Ver 7.2 (dated July 19, 2023).

Congenital diaphragmatic hernia-associated pulmonary hypertension.

Congenital diaphragmatic hernia (CDH) is characterized by a developmental insult which compromises cardiopulmonary embryology and results in a diaphragmatic defect, allowing abdominal organs to herniate into the hemithorax. Among the significant pathophysiologic components of this condition is pulmonary hypertension (PH), alongside pulmonary hypoplasia and cardiac dysfunction. Fetal pulmonary vascular development coincides with lung development, with the pulmonary vasculature evolving alongside lung maturation. However, in CDH, this embryologic development is impaired which, in conjunction with external compression, stifle pulmonary vascular maturation, leading to reduced lung density, increased muscularization of the pulmonary vasculature, abnormal vascular responsiveness, and altered molecular signaling, all contributing to pulmonary arterial hypertension. Understanding CDH-associated PH (CDH-PH) is crucial for development of novel approaches and effective management due to its significant impact on morbidity and mortality. Antenatal and postnatal diagnostic methods aid in CDH risk stratification and, specifically, pulmonary hypertension, including fetal imaging and gas exchange assessments. Management strategies include lung protective ventilation, fluid optimization, pharmacotherapies including pulmonary vasodilators and hemodynamic support, and extracorporeal life support (ECLS) for refractory cases. Longitudinal re-evaluation is an important consideration due to the complexity and dynamic nature of CDH cardiopulmonary physiology. Emerging therapies such as fetal endoscopic tracheal occlusion and pharmacological interventions targeting key CDH pathophysiological mechanisms show promise but require further investigation. The complexity of CDH-PH underscores the importance of a multidisciplinary approach for optimal patient care and improved outcomes.

PDA management strategies and pulmonary hypertension in extreme preterm infants with bronchopulmonary dysplasia.

BACKGROUND: Premature infants are at risk for developing pulmonary hypertension (PH) in the context of bronchopulmonary dysplasia (BPD). Studies suggest a potential link between prolonged patent ductus arteriosus (PDA) exposure and BPD-PH, though management strategies remain controversial. METHODS: Retrospective echocardiographic evaluation of newborns <29 weeks gestational age with BPD at two distinct centers. Primary objective was to evaluate the relationship between center-specific PDA management strategies (interventional or conservative) and the prevalence of BPD-PH. BPD was defined as oxygen or respiratory support at 36 weeks post-menstrual age (PMA). The presence of PH was defined as either an estimated sPAP of ≥40 mmHg or sEI ≥1.3. Center A has a conservative PDA policy. Center B has a targeted interventional policy. RESULTS: PH rates were similar between sites (21% vs 17%), while rates of PDA treatment was different (7% vs 81). Adjusted models did not demonstrate an association for center or PDA treatment exposure for PH and EI, although infants from Center A had echocardiography evidence of higher systolic eccentricity index (EI; 1.12 ± 0.19 vs 1.06 ± 0.15, p = 0.04). Markers of RV function (TAPSE and RV-FAC) were similar between groups. CONCLUSION: In preterm infants <29 weeks with BPD, conservative PDA treatment policy was not associated with higher rate of pulmonary hypertension diagnosis. IMPACT: The association between PDA-management approaches and the occurrence of BPD-associated pulmonary vascular disease in premature infants has sparsely been described. We found that a conservative policy, regarding the PDA, was not associated with an increase in pulmonary hypertension diagnosis. We identified that, in patients with BPD, echocardiographic metrics of LV performance were lower.

Enhanced perfluorooctanoic acid (PFOA) degradation by electrochemical activation of peroxydisulfate (PDS) during electrooxidation for water treatment.

Improved treatment of per- and polyfluoroalkyl substances (PFAS) in water is critically important in light of the proposed United States Environmental Protection Agency (USEPA) drinking water regulations at ng L-1 levels. The addition of peroxymonosulfate (PMS) during electrooxidation (EO) can remove and destroy PFAS, but ng L-1 levels have not been tested, and PMS itself can be toxic. The objective of this research was to test peroxydisulfate (PDS, an alternative to PMS) activation by boron-doped diamond (BDD) electrodes for perfluorooctanoic acid (PFOA) degradation. The influence of PDS concentration, temperature, and environmental water matrix effects, and PFOA concentration on PDS-EO performance were systematically examined. Batch reactor experiments revealed that 99 % of PFOA was degraded and 69 % defluorination was achieved, confirming PFOA mineralization. Scavenging experiments implied that sulfate radicals (SO4-) and hydroxyl radicals (HO) played a more important role for PFOA degradation than 1O2 or electrons (e-). Further identification of PFOA degradation and transformation products by liquid chromatography-mass spectrometry (LC-MS) analysis established plausible PFOA degradation pathways. The analysis corroborates that direct electron transfers at the electrode initiate PFOA oxidation and SO4- improves overall treatment by cleaving the CC bond between the C7F15 and COOH moieties in PFOA, leading to possible products such as C7F15 and F-. The perfluoroalkyl radicals can be oxidized by SO4- and HO, resulting in the formation of shorter chain perfluorocarboxylic acids (e.g., perfluorobutanoic acid [PFBA]), with eventual mineralization to CO2 and F-. At an environmentally relevant low initial concentration of 100 ng L-1 PFOA, 99 % degradation was achieved. The degradation of PFOA was slightly affected by the water matrix as less removal was observed in an environmental river water sample (91 %) compared to tests conducted in Milli-Q water (99 %). Overall, EO with PDS provided a destructive approach for the elimination of PFOA.

Exposure to persistent hemodynamically significant patent ductus arteriosus is associated with retinopathy of prematurity.

BACKGROUND: Hemodynamically significant patent ductus arteriosus (hsPDA) shunt may predispose infants to retinopathy of prematurity (ROP) because of its higher preductal cardiac output and blood oxygen content, which may augment ocular oxygen delivery. METHODS: A retrospective cohort study of preterm infants, born at <27 weeks' gestation and admitted at <24h postnatal age to a large quaternary referral was conducted. The primary composite outcome was death at <32 weeks or moderate-to-severe ROP (≥stage 2 or requiring treatment) in either eye. Secondary outcomes included ROP requiring treatment, and any ROP. Univariate analysis of patient characteristics and outcomes was performed as well as logistic regression. A receiver operating characteristics curve was generated for the outcome of ROP ≥stage 2 or requiring treatment. RESULTS: A total of 91 patients were screened, of whom 86 (54 hsPDA, 32 controls) were eligible for inclusion. hsPDA patients were younger and lighter at birth and had a higher burden of hyperglycemia and respiratory illness. The rates of the composite outcome (death <32 weeks or moderate-to-severe ROP) and of any ROP were more frequent in the hsPDA group. hsPDA shunt exposure was independently associated with development of any ROP among survivors to assessment (P = 0.006). PDA cumulative exposure score of 78 (clinical equivalent = 7 days high-volume shunt exposure) predicts moderate-to-severe ROP with 80% sensitivity and 78% specificity. CONCLUSIONS: Among infants <27 weeks, hsPDA shunt is associated with increased risks of a composite outcome of death or moderate-to-severe ROP, as well as ROP of any stage. Shunt modulation as a strategy to reduce ROP represents a biologically plausible avenue for investigation.

Cardiorespiratory Instability after Percutaneous Patent Ductus Arteriosus Closure: A Multicenter Cohort Study.

OBJECTIVE: To evaluate postprocedural clinical characteristics of preterm infants undergoing transcatheter patent ductus arteriosus (PDA) closure, including oxygenation/ventilation failure and cardiovascular compromise. STUDY DESIGN: Multicenter retrospective cohort study of preterm infants who were ≤2 kg at the time of percutaneous PDA closure between August 2018 and July 2021. Indices of cardiorespiratory stability were collected pre-closure, immediately post-closure, and subsequently averaged every 4 hours for the first 24 hours post-procedure. The primary outcome was incidence of post-transcatheter cardiorespiratory syndrome: composite of hemodynamic instability (defined by systemic hypotension, systemic hypertension, or use of new inotropes/vasopressors in the first 24 hours after catheterization) and at least one of the following: (i) ventilation failure or (ii) oxygenation failure. RESULTS: A total of 197 patients were included with a median [IQR] age and weight at catheterization of 34 [25, 43] days and 1090 [900, 1367] grams, respectively. The primary composite outcome of post-transcatheter cardiorespiratory syndrome was reported in 46 (23.3%). CONCLUSION: Post-transcatheter cardiorespiratory syndrome is characterized primarily by systemic hypertension and oxygenation failure, with a very low incidence of hypotension and need for inotropes.

Guidelines and Recommendations for Targeted Neonatal Echocardiography and Cardiac Point-of-Care Ultrasound in the Neonatal Intensive Care Unit: An Update from the American Society of Echocardiography.

Targeted neonatal echocardiography (TNE) involves the use of comprehensive echocardiography to appraise cardiovascular physiology and neonatal hemodynamics to enhance diagnostic and therapeutic precision in the neonatal intensive care unit. Since the last publication of guidelines for TNE in 2011, the field has matured through the development of formalized neonatal hemodynamics fellowships, clinical programs, and the expansion of scientific knowledge to further enhance clinical care. The most common indications for TNE include adjudication of hemodynamic significance of a patent ductus arteriosus, evaluation of acute and chronic pulmonary hypertension, evaluation of right and left ventricular systolic and/or diastolic function, and screening for pericardial effusions and/or malpositioned central catheters. Neonatal cardiac point-of-care ultrasound (cPOCUS) is a limited cardiovascular evaluation which may include line tip evaluation, identification of pericardial effusion and differentiation of hypovolemia from severe impairment in myocardial contractility in the hemodynamically unstable neonate. This document is the product of an American Society of Echocardiography task force composed of representatives from neonatology-hemodynamics, pediatric cardiology, pediatric cardiac sonography, and neonatology-cPOCUS. This document provides (1) guidance on the purpose and rationale for both TNE and cPOCUS, (2) an overview of the components of a standard TNE and cPOCUS evaluation, (3) disease and/or clinical scenario-based indications for TNE, (4) training and competency-based evaluative requirements for both TNE and cPOCUS, and (5) components of quality assurance. The writing group would like to acknowledge the contributions of Dr. Regan Giesinger who sadly passed during the final revisions phase of these guidelines. Her contributions to the field of neonatal hemodynamics were immense.

Asphyxia, Therapeutic Hypothermia, and Pulmonary Hypertension.

Neonates with a perinatal hypoxic insult and subsequent neonatal encephalopathy are at risk of acute pulmonary hypertension (aPH) in the transitional period. The phenotypic contributors to aPH following perinatal asphyxia include a combination of hypoxic vasoconstriction of the pulmonary vascular bed, right heart dysfunction, and left heart dysfunction. Therapeutic hypothermia is the standard of care for neonates with moderate-to-severe hypoxic ischemic encephalopathy. This review summarizes the underlying risk factors, causes of aPH in neonates with perinatal asphyxia, discusses the unique phenotypical contributors to disease, and explores the impact of the initial insult and subsequent therapeutic hypothermia on aPH.

Targeted Neonatal Echocardiography in the Management of Neonatal Pulmonary Hypertension.

Pulmonary hypertension (PH) in neonates, originating from a range of disease states with heterogeneous underlying pathophysiology, is associated with significant morbidity and mortality. Although the final common pathway is a state of high right ventricular afterload leading to compromised cardiac output, multiple hemodynamic phenotypes exist in acute and chronic PH, for which cardiorespiratory treatment strategies differ. Comprehensive appraisal of pulmonary pressure, pulmonary vascular resistance, cardiac function, pulmonary and systemic blood flow, and extrapulmonary shunts facilitates delivery of individualized cardiovascular therapies in affected newborns.