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.

Lessons from the Pandemic: Role of Percutaneous ECMO and Balloon Atrial Septostomy in Multi-System Inflammatory Syndrome in Children.

Multi-system inflammatory syndrome in children (MIS-C) in the setting of COVID-19 can be associated with severe cardiopulmonary dysfunction. This clinical deterioration may sometimes necessitate veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. We describe an algorithmic approach including the role of balloon atrial septostomy in this cohort. This is the first reported series of percutaneous VA-ECMO in pediatric patients with MIS-C for better outcomes. The lessons from this approach can be replicated in other pediatric clinical conditions and adds to the armament of multiple pediatric specialties.

Efficacy of Sildenafil in Infants with Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is a common comorbidity in infants with bronchopulmonary dysplasia (BPD). Sildenafil is a widely recognized therapy for PH, but its efficacy in infants with BPD is questionable. We propose to assess the efficacy of sildenafil in BPD-associated PH as evaluated based on transthoracic echocardiography (TTE) changes and clinical measures. Methods: Data were retrospectively and prospectively collected. Inclusion criteria were gestational age (GA) < 32 weeks, birth weight (BW) < 1500 g with severe BPD, diagnosis of PH via TTE on sildenafil treatment. PH was evaluated via TTE, which was performed monthly after 36 weeks post-menstrual age (PMA) as a standard of care, and re-reviewed by a single pediatric cardiologist, who was blind to the initial reading. Results: In total, 19 patients were enrolled in the study, having a median GA of 24 3/7 weeks (IQR 23 5/7-25 5/7) and a median BW of 598 g (IQR 572-735). Sildenafil treatment was started at a median PMA of 40.4 weeks. The median respiratory severity score (RSS) at 28 d was 6.5, RSS and FiO2 showed improvement about 12 weeks after starting sildenafil treatment. Conclusions: Improvement in PH was noted via TTE, and patients had improvement in their RSS and FiO2 after prolonged therapy. However, TTE improvements did not correlate with clinical improvements.

Elevated Copeptin Levels Are Associated with Heart Failure Severity and Adverse Outcomes in Children with Cardiomyopathy.

In children with cardiomyopathy, the severity of heart failure (HF) varies. However, copeptin, which is a biomarker of neurohormonal adaptation in heart failure, has not been studied in these patients. In this study, we evaluated the correlation of copeptin level with functional HF grading, B-type natriuretic peptide (BNP), and echocardiography variables in children with cardiomyopathy. Furthermore, we determined if copeptin levels are associated with adverse outcomes, including cardiac arrest, mechanical circulatory support, heart transplant, or death. In forty-two children with cardiomyopathy with a median (IQR) age of 13.1 years (2.5-17.2) and a median follow-up of 2.5 years (2.2-2.7), seven (16.7%) children had at least one adverse outcome. Copeptin levels were highest in the patients with adverse outcomes, followed by the patients without adverse outcomes, and then the healthy children. The copeptin levels in patients showed a strong correlation with their functional HF grading, BNP level, and left ventricular ejection fraction (LVEF). Patients with copeptin levels higher than the median value of 25 pg/mL had a higher likelihood of experiencing adverse outcomes, as revealed by Kaplan-Meier survival analysis (p = 0.024). Copeptin level was an excellent predictor of outcomes, with an area under the curve of 0.861 (95% CI, 0.634-1.089), a sensitivity of 86%, and a specificity of 60% for copeptin level of 25 pg/mL. This predictive value was superior in patients with dilated and restrictive cardiomyopathies (0.97 (CI 0.927-1.036), p < 0.0001, n = 21) than in those with hypertrophic and LV non-compaction cardiomyopathies (0.60 (CI 0.04-1.16), p = 0.7, n = 21).

Long-Term Cardiovascular Outcomes of Multisystem Inflammatory Syndrome in Children Associated with COVID-19 Using an Institution Based Algorithm.

Cardiovascular involvement is a major cause of inpatient and intensive care unit morbidity related to Multisystem inflammatory syndrome in children (MIS-C). The objective of this study was to identify long-term cardiovascular manifestations of MIS-C. We included 80 consecutive patients admitted to the intensive care unit with MIS-C who were evaluated for a year in our follow-up clinic using an institution protocol. The outcome measures were cardiac biomarkers (troponin and BNP), electrocardiogram changes, echocardiographic findings cardiovascular magnetic resonance (CMR) and graded-exercise stress test (GXT) findings. The cohort included patients aged between 6 months and 17 years (median 9 years; 48.8% females). At the peak of the disease 81.3% had abnormal BNP and 58.8% had troponin leak which reduced to 33.8% and 18.8% respectively at discharge with complete normalization by 6 weeks post-discharge. At admission 33.8% had systolic dysfunction, which improved to 11.3% at discharge with complete resolution by 2 weeks. Coronary artery abnormalities were seen in 17.5% during the illness with complete resolution by 2 weeks post discharge except one (1.9%) with persistent giant aneurysm at 1 year-follow up. CMR was performed at 6 months in 23 patient and demonstrated 4 patients with persistent late gadolinium enhancement (17.4%). Normal exercise capacity with no ectopy was seen in the 31 qualifying patients that underwent a GXT. There is significant heterogeneity in the cardiovascular manifestations of MIS-C. Although majority of the cardiovascular manifestations resolve within 6 weeks, diastolic dysfunction, CAA and myocardial scar may persist in a small subset of patients warranting a structured long-term follow-up strategy.

Cardiovascular Magnetic Resonance in Children with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19: Institutional Protocol-Based Medium-Term Follow-up Study.

Multisystem inflammatory syndrome in children (MIS-C) secondary to COVID-19 infection in previously healthy children often results in subtle but persistent echocardiographic abnormalities despite complete clinical recovery. This study was done to investigate medium-term cardiovascular outcomes of patients with MIS-C using cardiovascular magnetic resonance imaging (CMR). This is a single-center retrospective study of patients aged less than 21 years, diagnosed with MIS-C who received an outpatient CMR, around 6 months after discharge. CMR was done in patients with significant troponin leak or depressed LVEF. CMR performed on a GE Signa HDxt 1.5 Tesla magnet with a myocarditis protocol. Diagnosis of myocarditis was determined by the original Lake Louise Criteria. There were 21 patients with a median age of 11 years, (IQR 8-13 years), who underwent CMR at median follow-up duration of 6 months (IQR 5-7 months). At the peak of illness during admission, there were 95.2% patients with abnormal Troponin I and BNP. By echocardiogram, 76.2% had left ventricular systolic dysfunction and 9.5% had coronary ectasia, which all resolved by 6 months. By CMR, there were five patients (23.8%) with abnormal left atrial volume, one patient (4.8%) with an abnormal indexed left ventricular end-diastolic volume, and three patients (15%) with abnormal LVEF. There was no evidence of myocardial edema in T2-weighted image sequence. There were three patients with persistent late gadolinium enhancement (14.3%). Follow-up CMR is a useful tool in diagnosing subtle myocardial abnormalities and guide necessity for future follow-up.

Feasibility and Safety of Percutaneous Cardiac Interventions for Congenital and Acquired Heart Defects in Infants ≤1000 g.

The transcatheter closure of patent ductus arteriosus (TCPC) has been demonstrated to be feasible even in infants weighing ≤1000 g. However, other percutaneous cardiac interventions (PCI) for such small infants born with congenital heart defects (CHD) or acquired heart defects (AHD) have not been well described. The purpose of this study was to describe the feasibility and safety of PCI in infants ≤1000 g. A retrospective review was conducted between June 2015 and May 2021, looking at 148 consecutive PCIs performed on infants weighing ≤1000 g at the time of the procedure. The procedural success rate was 100%. The major adverse event (AE) rate for TCPC was 3%, while there were no major AEs for other PCI. It is feasible to perform PCIs in infants weighing ≤1000 g with CHD and AHD using currently available technologies.

Echocardiographic versus Angiographic Measurement of the Patent Ductus Arteriosus in Extremely Low Birth Weight Infants and the Utility of Echo Guidance for Transcatheter Closure.

BACKGROUND: Transthoracic echocardiography (TTE) is increasingly utilized for guiding transcatheter closure of patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. The objectives of this study were to compare PDA size measurements by TTE with angiographic measurements and to describe TTE techniques used in guiding transcatheter PDA closure (TCPC) in ELBW infants. METHODS: One hundred twenty-five consecutive ELBW infants (gestational age < 27 weeks, birth weight < 1 kg) who underwent TCPC before 8 weeks of age under TTE guidance were included. Patent ductus arteriosus sizes were measured from the procedural TTE and angiograms retrospectively by blinded observers. The TTE PDA diameters at the aortic (ED1) and pulmonary end (ED2) were compared with the corresponding angiographic diameters (CD1 and CD2). The TTE PDA lengths, obtained by two techniques (EL1, a straight line between ED1 and ED2; and EL2, a curvilinear line along the PDA), were compared with the PDA length by angiography (CL). Transthoracic echocardiography was used to guide accurate device positioning within the PDA. RESULTS: The procedure weight was 600-1,460 g. The TTE and angiographic PDA diameters were comparable (mean ED1 vs CD1 = 4.5 ± 0.68 vs 4.4 ± 0.85 mm, P = .26; and mean ED2 vs CD2 = 3.1 ± 0.72 vs 3.2 ± 0.94 mm, P = .14). The angiographic length was underestimated by EL1 by 2.6 ± 1.6 mm (P < .0001), while EL2 estimated it better (mean EL2 vs CL = 11.0 ± 1.83 vs 10.8 ± 2.15 mm; P = .40). Transcatheter PDA closure was successful in 100% of the cases using TTE guidance. There were no intraprocedural complications. CONCLUSIONS: Transthoracic echocardiography guidance during TCPC in ELBW infants eliminates the need for aortograms via femoral arterial access, preventing the complications associated with it. Transthoracic echocardiography PDA measurements are comparable to angiographic measurements, thereby assisting in appropriate device size selection.

Hemodynamic and clinical consequences of early versus delayed closure of patent ductus arteriosus in extremely low birth weight infants.

OBJECTIVES: To describe changes in hemodynamics, respiratory support, and growth associated with transcatheter PDA closure (TCPC) in ELBW infants, stratified by postnatal age at treatment. STUDY DESIGN: This is an observational study of ELBW infants who underwent TCPC at ≤4 weeks (Group-1; n = 34), 4-8 weeks (Group-2; n = 33), and >8 weeks of age (Group-3; n = 33). Hemodynamic assessment was performed during TCPC. Multivariate Cox-proportionate-hazard modeling was used to identify factors associated with respiratory severity score (RSS) > 2 for >30 days following TCPC. RESULTS: In comparison with Group-1, Group-3 infants had higher pulmonary vascular resistance (PVRi = 3.3 vs. 1.6 WU*m2; P = 0.01), less weight gain between 4 and 8 weeks of age (16 vs. 25 g/day) and took longer to achieve RSS < 2 (median 81 vs. 20 days; P = 0.001). RSS > 2 for >30 days was associated with TCPC > 8 weeks (OR = 3.2, 95% CI: 1.75-5.8; p = 0.03) and PVRi ≥ 3 (OR = 4.5, 95% CI: 2.7-8.9; p < 0.01). CONCLUSION: ELBW infants may benefit from PDA closure within the first 4 weeks of life in order to prevent early onset pulmonary vascular disease, promote faster growth, and for quicker weaning of ventilator and oxygen support.

Pulmonary Hypertension with Prolonged Patency of the Ductus Arteriosus in Preterm Infants.

There continues to be a reluctance to close the patent ductus arteriosus (PDA) in premature infants. The debate on whether the short-term outcomes translate to a difference in long-term benefits remains. This article intends to review the pulmonary vasculature changes that can occur with a chronic hemodynamically significant PDA in a preterm infant. It also explains the rationale and decision-making involved in a diagnostic cardiac catheterization and transcatheter PDA closure in these preterm infants.

Management of Patent Ductus Arteriosus in Premature Infants in 2020.

The patent ductus arteriosus (PDA) is the most commonly found cardiac condition in neonates. While there have been several studies and thousands of publications on the topic, the decision to treat the PDA is still strongly debated among cardiologists, surgeons, and neonatologists. This is in part due to the shortage of long-term benefits with the interventions studied. Practice variations still exist within sub-specialties and centers. This article briefly summarizes the history, embryology and histology of the PDA. It also succinctly discusses the hemodynamic significance of a PDA which builds the framework to review all the available literature on PDA closure in premature infants, though not a paradigm shift just yet; it introduces transcatheter PDA closure (TCPC) as a possible armament to the clinician for this age-old problem.

Pulmonary hypertension during respiratory syncytial virus bronchiolitis: a risk factor for severity of illness.

BACKGROUND: Respiratory syncytial virus infection is the most frequent cause of acute lower respiratory tract disease in infants. A few reports have suggested that pulmonary hypertension is associated with increased severity of respiratory syncytial virus infection. We sought to determine the association between the pulmonary hypertension detected by echocardiography during respiratory syncytial virus bronchiolitis and clinical outcomes. METHODS: We retrospectively reviewed 154 children admitted with respiratory syncytial virus bronchiolitis who had an echocardiography performed during the admission. The association between pulmonary hypertension and clinical outcomes including mortality, intensive care unit (ICU) admission, prolonged ICU stay (>10 days), tracheal intubation, and need of high frequency oscillator ventilation was evaluated. RESULTS: Echocardiography detected pulmonary hypertension in 29 patients (18.7%). Pulmonary hypertension was observed more frequently in patients with congenital heart disease (CHD) (n = 11/33, 33%), chronic lung disease of infancy (n = 12/25, 48%), prematurity (<37 weeks gestational age, n = 17/59, 29%), and Down syndrome (n = 4/10, 40%). The presence of pulmonary hypertension was associated with morbidity (p < 0.001) and mortality (p = 0.02). However, in patients without these risk factors (n = 68), pulmonary hypertension was detected in five patients who presented with shock or poor perfusion. Chronic lung disease was associated with pulmonary hypertension (OR = 5.9, 95% CI 2.2-16.3, p = 0.0005). Multivariate logistic analysis demonstrated that pulmonary hypertension is associated with ICU admission (OR = 6.4, 95% CI 2.2-18.8, p = 0.0007), intubation (OR = 4.7, 95% CI 1.8-12.3, p = 0.002), high frequency oscillator ventilation (OR = 8.4, 95% CI 2.95-23.98, p < 0.0001), and prolonged ICU stay (OR = 4.9, 95% CI 2.0-11.7, p = 0.0004). CONCLUSIONS: Pulmonary hypertension detected by echocardiography during respiratory syncytial virus infection was associated with increased morbidity and mortality. Chronic lung disease was associated with pulmonary hypertension detected during respiratory syncytial virus bronchiolitis. Routine echocardiography is not warranted for previously healthy, haemodynamically stable patients with respiratory syncytial virus bronchiolitis.

Effect of patent ductus arteriosus on pulmonary vascular disease.

The hemodynamic effects of a patent ductus arteriosus (PDA) are well known including systemic hypoperfusion and volume overload on the left ventricle. This article aims to provide a review of the long-standing effect of a hemodynamically significant PDA on the pulmonary vasculature and the role of cardiac catheterization in preterm infants with a PDA and pulmonary hypertension.

Effect of patent ductus arteriosus on the heart in preterm infants.

There continues to be controversy on the long-term effects of a patent ductus arteriosus (PDA) and its management. However, the hemodynamic effects of a large PDA in a preterm infant are well known. This article aims to provide insight into the adaptive changes and remodeling effects of a PDA on the myocardium in preterm infants.

A comprehensive program for preterm infants with patent ductus arteriosus.

OBJECTIVES: Patent ductus arteriosus (PDA) is a common finding in preterm infants. A hemodynamically significant PDA may require intervention for closure. This article aims to describe a transcatheter PDA closure (TCPC) program for preterm infants and the components of a comprehensive outpatient follow-up strategy. SETTING: A multidisciplinary team approach including neonatology, cardiology, anesthesiology, medical transport team, pulmonology, cardiac surgery, neurodevelopmental specialist, nutrition, speech therapy, social work, research collaborators, and other health care specialists is integral to the dedicated care and promotion of wellness of extremely low birth weight (ELBW) infants. PATIENTS: To date, we have performed TCPC on 134 ELBW infants weighing <2 kg at the time of the procedure, 54 of whom were <1 kg with the smallest weighing 640 g with a median gestation age of 25 weeks (range 23-27 weeks). INTERVENTIONS: A comprehensive follow-up strategy with the creation of the Memphis PDA Clinic was implemented. OUTCOME MEASURES: Respiratory support, tolerance of enteral feeds, growth, and neurodevelopmental progress are indicators of favorable outcomes. RESULTS: TCPC has benefited ELBW infants with faster weaning off the ventilator, increase in enteral feedings, and somatic growth with the overall shortening of the hospital length of stay. The Memphis PDA Clinic has ensured optimal postdischarge follow-up to improve long-term outcomes. CONCLUSIONS: TCPC is a safe and effective alternative to manage ELBW infants with a hemodynamically significant PDA. Comprehensive follow-up after discharge provided in a multispecialty clinic developed specifically for this unique population has been successful in improving outcomes.

Can transcatheter PDA closure be performed in neonates ≤1000 grams? The Memphis experience.

OBJECTIVE: Advancements in transcatheter technology have now made it possible to safely close patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. The objective of this article is to describe our technique for transcatheter PDA closure (TCPC) in ELBW infants. DESIGN: The techniques employed are very specific to this population and are drastically different when compared to the procedure performed in patients weighing >5 kg. SETTING: A multidisciplinary team approach should be taken to evaluate and manage ELBW infants in order to achieve success. It is important that specific techniques with venous-only approach outlined in this article be followed to achieve optimal results with low risk of complications. PATIENTS: To date, in Memphis, 55 ELBW infants have had successful TCPC at a weight of ≤1000 g with minimal procedure-related complications. INTERVENTIONS: It is important that specific techniques with venous-only approach outlined in this article be followed to achieve optimal results with low risk of complications. OUTCOME MEASURES: This procedure entails a steep learning curve and should be limited to specialized centers with expertise in these thanscatheter procedures. RESULTS: There has been 100% procedural success of performing TCPC in children ≤1000 g. There have been only two procedure-related complications which happened to the first two patients, ≤1000 g, that we performed TCPC on. CONCLUSIONS: It is feasible and probably safe to perform TCPC in children ≤1000 g. The techniques described in this article represent our institutional experience and have helped us improve clinical outcomes in ELBW infants.