Prenatal Predictors for Pulmonary Balloon Valvuloplasty in the Newborn.

Pulmonary balloon valvuloplasty (PBV) is the treatment of choice for subjects with isolated pulmonary valve stenosis (IPS). The purpose of this study was to define fetal echocardiographic features associated with an inpatient PBV prior to newborn hospital discharge and characterize resource utilization of IPS fetuses among participating centers. Six center, retrospective case series of singleton fetuses identified between 2010 and 2020 with IPS. Third-trimester echocardiogram data was compared with postnatal data, included pulmonary valve Doppler velocities, pulmonary valve insufficiency and ductus arteriosus flow direction. Comparison between subjects who underwent inpatient PBV during their newborn hospital admission versus those infants referred for outpatient PBV after initial hospital discharge. We analyzed data by logistic regression, student t test and Chi-Square testing with a p value of ≤ 0.05 considered statistically significant. Forty-nine IPS fetuses were identified. Thirty-eight (78%) underwent inpatient PBV at 5 (range 1-58) days and 11 (22%) underwent outpatient PBV at 51.8 (11-174) days. Newborns requiring an inpatient PBV were more likely to have one or more characteristics on 3rd-trimester fetal echocardiogram: left to right or bidirectional ductus arteriosus flow (61% vs 0%), and/or a peak pulmonary valve velocity > 3.0 m/s (odds ratio 16.9, 95% confidence interval 3.02-94.17) with a sensitivity of 90.4% and specificity of 97.7%. Ductus arteriosus flow direction and pulmonary valve peak velocity in the 3rd trimester can successfully predict the need for newborn inpatient PBV. We speculate these findings may be useful in choosing delivery site for the pregnancy complicated by fetal IPS.

Prematurity and Pulmonary Vein Stenosis: The Role of Parenchymal Lung Disease and Pulmonary Vascular Disease.

Pulmonary vein stenosis (PVS) has emerged as a critical problem in premature infants with persistent respiratory diseases, particularly bronchopulmonary dysplasia (BPD). As a parenchymal lung disease, BPD also influences vascular development with associated pulmonary hypertension recognized as an important comorbidity of both BPD and PVS. PVS is commonly detected later in infancy, suggesting additional postnatal factors that contribute to disease development, progression, and severity. The same processes that result in BPD, some of which are inflammatory-mediated, may also contribute to the postnatal development of PVS. Although both PVS and BPD are recognized as diseases of inflammation, the link between them is less well-described. In this review, we explore the relationship between parenchymal lung diseases, BPD, and PVS, with a specific focus on the epidemiology, clinical presentation, risk factors, and plausible biological mechanisms in premature infants. We offer an algorithm for early detection and prevention and provide suggestions for research priorities.

Implementation of Appropriate Use Criteria for Transthoracic Echocardiography in Follow-Up Care of Pediatric Patients with Congenital Heart Disease.

BACKGROUND: Indications for transthoracic echocardiography (TTE) from the 2020 Appropriate Use Criteria (AUC) for congenital heart disease (CHD) were incorporated into the institutional electronic ordering system as a clinical decision support tool. The purpose of this study was to evaluate the utilization of TTE and factors affecting the appropriateness of orders for TTE during follow-up care of patients with CHD. METHODS: All transthoracic echocardiographic studies performed during follow-up clinic visits from May 1, 2020, to November 30, 2020, were included. Indications for TTE were rated appropriate, may be appropriate, or rarely appropriate on the basis of the AUC and unclassifiable if the indication was not in the document but related to included lesions. CHD was graded as simple, moderate, or complex on the basis of the Bethesda classification. Logistic regression was used to determine the association of ratings with patient age, insurance status, CHD complexity, and clinician experience and specialty. RESULTS: Of the 5,158 studies, 3,979 (77.2%) were for CHD included in the AUC document, 322 (8%) were unclassifiable, 37 (0.7%) were for CHD not in the document, and 1,142 (22.1%) were for non-CHD indications. Of the 3,657 transthoracic echocardiographic examinations to which AUC ratings could be applied, 95.6% were rated appropriate, 2.4% may be appropriate, and 2.0% rarely appropriate. The highest utilization of TTE was for follow-up of ventricular septal defects, left ventricular outflow tract obstruction, and single ventricles; 46% for unrepaired CHD; 78% for routine surveillance; and the remaining for changes in clinical status. On multivariable analysis, the only significant factor associated with may be appropriate and rarely appropriate ratings was simple CHD (odds ratio, 11.58; 95% CI, 5.36 - 24.98; P < .001). CONCLUSIONS: Three quarters of transthoracic echocardiographic studies ordered during follow-up care in pediatric cardiology clinics are for indications related to CHD. Most examinations for follow-up of CHD were for routine surveillance and indications rated appropriate. Orders for TTE for may be appropriate and rarely appropriate ratings were associated with simple CHD. Although the 2020 AUC document successfully stratifies the majority of indications related to CHD, future documents should consider the unclassifiable CHD indications and the non-CHD indications.

Systemic Sirolimus Therapy for Infants and Children With Pulmonary Vein Stenosis.

BACKGROUND: Anatomic interventions for pulmonary vein stenosis (PVS) in infants and children have been met with limited success. Sirolimus, a mammalian target of rapamycin inhibitor, has demonstrated promise as a primary medical therapy for PVS, but the impact on patient survival is unknown. OBJECTIVES: The authors sought to investigate whether mTOR inhibition with sirolimus as a primary medical therapy would improve outcomes in high-risk infants and children with PVS. METHODS: In this single-center study, patients with severe PVS were considered for systemic sirolimus therapy (SST) following a strict protocol while receiving standardized surveillance and anatomic therapies. The SST cohort was compared with a contemporary control group. The primary endpoint for this study was survival. The primary safety endpoint was adverse events (AEs) related to SST. RESULTS: Between 2015 and 2020, our PVS program diagnosed and treated 67 patients with ≥moderate PVS. Of these, 15 patients were treated with sirolimus, whereas the remaining patients represent the control group. There was 100% survival in the SST group compared with 45% survival in the control group (log-rank p = 0.004). A sensitivity analysis was completed to address survival bias using median time from diagnosis of PVS to SST. A survival advantage persisted (log-rank p = 0.027). Two patients on sirolimus developed treatable AEs. Patients in the SST group underwent frequent transcatheter interventions with 3.7 catheterizations per person-year (25th to 75th percentile: 2.7 to 4.4 person-years). Median follow up time was 2.2 years (25th to 75th percentile: 1.2 to 2.9 years) in the SST group versus 0.9 years (25th to 75th percentile: 0.5 to 2.7 years) in the control group. CONCLUSIONS: The authors found a survival benefit associated with SST in infants and children with moderate-to-severe PVS. This survival benefit persisted after adjusting the analysis for survival bias. There were 2 mild AEs associated with SST during the study period; both patients were able to resume therapy without recurrence.

Identifying Non-invasive Tools to Distinguish Acute Myocarditis from Dilated Cardiomyopathy in Children.

There is often a diagnostic dilemma in pediatric patients presenting with depressed ventricular function, as myocarditis and dilated cardiomyopathy (DCM) of other etiologies can appear very similar. Accurate identification is critical to guide treatment and to provide families with the most accurate expectation of long-term outcomes. The objective of this study was to identify patterns of clinical presentation and to assess non-invasive measures to differentiate patients with acute myocarditis from other forms of DCM. We identified all children (< 18 years) from our institution with a diagnosis of idiopathic DCM or myocarditis based on endomyocardial biopsy or explant pathology (1996-2015). Characteristics at the time of presentation were compared between patients with a definite diagnosis of myocarditis and those with idiopathic DCM. Data collected included clinical and laboratory data, radiography, echocardiography, and cardiac catheterization data. A total of 58 patients were included in the study; 46 (79%) with idiopathic DCM and 12 (21%) with acute myocarditis. Findings favoring a diagnosis of myocarditis included a history of fever (58 vs. 15%, p = 0.002), arrhythmia (17 vs. 0%, p = 0.003), higher degree of cardiac enzyme elevation, absence of left ventricular dilation (42 vs. 7%, p = 0.002), segmental wall motion abnormalities (58 vs. 13%, p = 0.001), lower left ventricular dimension z-score (3.7 vs. 5.2, p = 0.031), and less severe depression of left ventricular systolic function. There are notable differences between patients with myocarditis and other forms of DCM that can be detected non-invasively at the time of presentation without the need for endomyocardial biopsy. These data suggest that it may be possible to develop a predictive model to differentiate myocarditis from other forms of DCM using non-invasive measures.

Pulmonary hypertension in the premature infant population: Analysis of echocardiographic findings and biomarkers.

OBJECTIVE: Extremely low gestational age neonates (ELGANs) are at risk for pulmonary hypertension (PH). We hypothesized that PH, defined by echocardiogram at 36 weeks gestational age (GA), would associate with respiratory morbidity, increased oxidant stress, and reduced nitric oxide production. STUDY DESIGN: ELGANs in the Vanderbilt fraction of the Prematurity and Respiratory Outcomes Program (PROP) who had echocardiograms at 36 ± 1 weeks GA were studied. Echocardiogram features of PH were compared with clinical characteristics as well as markers of oxidant stress and components of the nitric oxide pathway. Biomarkers were obtained at enrollment (median day 3), 7, 14, and 28 days of life. RESULTS: Sixty of 172 infants had an echocardiogram at 36 weeks; 11 had evidence of PH. Infants did not differ by PH status in regards to demographics, respiratory morbidity, or oxidant stress. However, odds of more severe PH were significantly higher in infants with higher nitric oxide metabolites (NOx) at enrollment and with a lower citrulline level at day 7. CONCLUSIONS: Respiratory morbidity may not always associate with PH at 36 weeks among ELGANs. However, components of nitric oxide metabolism are potential biologic markers of PH in need of further study.