Objectives
Extrapulmonary manifestations of bronchiolitis have been previously studied, with some identifying right ventricle (RV) diastolic/systolic dysfunction. We hypothesized that severe cases of ...bronchiolitis would have cardiac dysfunction resulting an increase in N‐terminal pro‐hormone B‐type natriuretic peptide (NT‐proBNP) values and worse outcomes. Therefore, the objective was to evaluate the existence of cardiac dysfunction and to determine its association with severe bronchiolitis.
Methods
This prospective cohort study included children hospitalized for bronchiolitis under 1‐year old between January 2019 and March 2020. At admission, an echocardiography was performed and plasma levels of NT‐proBNP were measured. To analyze outcomes, the cohort was divided into two groups based on the need for positive pressure respiratory support (PPRS), and both were compared to healthy infants. Statistics: bivariant analysis, significant differences p < 0.05.
Results
One hundred eighty‐one patients were included; median age was 2 months. Seventy‐three patients required PPRS. Compared to controls, patients requiring PPRS showed worse RV systolic function, with lower tricuspid annular‐plane systolic excursion (p = 0.002) and parameters of worse right and left diastolic function (trans‐tricuspid E and A wave p = 0.004 and p = 0.04, respectively and tricuspid tissue doppler imaging TDI e′ p = 0.003, trans‐mitral E and mitral TDI a′ p = 0.02 and p = 0.005, respectively). An NT‐ProBNP greater than 3582 pg/dl predicts the need for longer necessity of PPRS in patients younger than 2 months.
Conclusions
In addition to the expected RV systolic dysfunction, patients with severe bronchiolitis have parameters of global diastolic worse function possibly secondary to intrinsic myocardial involvement. NT‐ProBNP values at admission had strong discriminatory power to predict worse outcomes.
Animal models showed that angiogenesis is related to abnormal heart development. Our objectives were to ascertain whether a relationship exists between congenital heart defects (CHDs) and ...angiogenic/anti-angiogenic imbalance in maternal and foetal blood and study the expression of angiogenic factors in the foetal heart.
Maternal and cord blood placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) were compared in 65 cases of CHD and 204 normal controls. Angiogenic factor expression and markers of hypoxia were measured in heart tissue from 23 CHD foetuses and 8 controls. In the CHD group, compared with controls, plasma PlGF levels were significantly lower (367 ± 33 vs. 566 ± 26 pg/mL; P < 0.0001) and sFlt-1 significantly higher (2726 ± 450 vs. 1971 ± 130 pg/mL, P = 0.0438). Foetuses with CHD had higher cord plasma sFlt-1 (442 ± 76 vs. 274 ± 26 pg/mL; P = 0.0285) and sEng (6.76 ± 0.42 vs. 4.99 ± 0.49 ng/mL, P = 0.0041) levels. Expression of vascular endothelial growth factor (VEGF), sFlt-1, markers of chronic hypoxia, and antioxidant activity were significantly higher in heart tissue from CHD foetuses compared with normal hearts (VEGF, 1.59-fold; sFlt-1, 1.92-fold; hypoxia inducible factor (HIF)-2α, 1.45-fold; HO-1, 1.62-fold; SOD1, 1.31-fold).
An intrinsically angiogenic impairment exists in CHD that appears to be present in both the maternal and foetal circulation and foetal heart. Our data suggest that an imbalance of angiogenic-antiangiogenic factors is associated with developmental defects of the human heart.
Point-of-care ultrasound (POCUS) is nowadays an essential tool in critical care. Its role seems more important in neonates and children where other monitoring techniques may be unavailable. POCUS ...Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) aimed to provide evidence-based clinical guidelines for the use of POCUS in critically ill neonates and children.
Creation of an international Euro-American panel of paediatric and neonatal intensivists expert in POCUS and systematic review of relevant literature. A literature search was performed, and the level of evidence was assessed according to a GRADE method. Recommendations were developed through discussions managed following a Quaker-based consensus technique and evaluating appropriateness using a modified blind RAND/UCLA voting method. AGREE statement was followed to prepare this document.
Panellists agreed on 39 out of 41 recommendations for the use of cardiac, lung, vascular, cerebral and abdominal POCUS in critically ill neonates and children. Recommendations were mostly (28 out of 39) based on moderate quality of evidence (B and C).
Evidence-based guidelines for the use of POCUS in critically ill neonates and children are now available. They will be useful to optimise the use of POCUS, training programs and further research, which are urgently needed given the weak quality of evidence available.
Multisystem inflammatory syndrome associated with the SARS-CoV-2 pandemic has recently been described in children (MIS-C), partially overlapping with Kawasaki disease (KD). We hypothesized that (a) ...MIS-C and prepandemic KD cytokine profiles may be unique and justify the clinical differences observed, and (b) SARS-CoV-2-specific immune complexes (ICs) may explain the immunopathology of MIS-C. Seventy-four children were included: 14 with MIS-C, 9 patients positive for SARS-CoV-2 by PCR without MIS-C (COVID), 14 with prepandemic KD, and 37 healthy controls (HCs). Thirty-four circulating cytokines were quantified in pretreatment serum or plasma samples and the presence of circulating SARS-CoV-2 ICs was evaluated in MIS-C patients. Compared with HCs, the MIS-C and KD groups showed most cytokines to be significantly elevated, with IFN-γ-induced response markers (including IFN-γ, IL-18, and IP-10) and inflammatory monocyte activation markers (including MCP-1, IL-1α, and IL-1RA) being the main triggers of inflammation. In linear discriminant analysis, MIS-C and KD profiles overlapped; however, a subgroup of MIS-C patients (MIS-Cplus) differentiated from the remaining MIS-C patients in IFN-γ, IL-18, GM-CSF, RANTES, IP-10, IL-1α, and SDF-1 and incipient signs of macrophage activation syndrome. Circulating SARS-CoV-2 ICs were not detected in MIS-C patients. Our findings suggest a major role for IFN-γ in the pathogenesis of MIS-C, which may be relevant for therapeutic management.
Neonates with complex congenital heart disease (CHD) demonstrate microstructural brain dysmaturation, but the relationship with structural network topology is unknown. We performed diffusion tensor ...imaging (DTI) in term neonates with CHD preoperatively (N = 61) and postoperatively (N = 50) compared with healthy term controls (N = 91). We used network topology (graph) analyses incorporating different weighted and unweighted approaches and subject‐specific white matter segmentation to investigate structural topology differences, as well as a voxel‐based analysis (VBA) to confirm the presence of microstructural dysmaturation. We demonstrate cost‐dependent network inefficiencies in neonatal CHD in the pre‐ and postoperative period compared with controls, related to microstructural differences. Controlling for cost, we show the presence of increased small‐worldness (hierarchical fiber organization) in CHD infants preoperatively, that persists in the postoperative period compared with controls, suggesting the early presence of brain reorganization. Taken together, topological microstructural dysmaturation in CHD infants is accompanied by hierarchical fiber organization during a protracted critical period of early brain development. Our methodology also provides a pipeline for quantitation of network topology changes in neonates and infants with microstructural brain dysmaturation at risk for perinatal brain injury.
To describe presentation, hospital course, and predictors of bad outcome in multisystem inflammatory syndrome in children (MIS-C).
Retrospective data review of a case series of children meeting the ...published definition for MIS-C who were discharged or died between March 1, 2020, and June 15, 2020, from 33 participating European, Asian, and American hospitals. Data were collected through a Web-based survey and included clinical, laboratory, electrocardiographic, and echocardiographic findings and treatment management.
We included 183 patients with MIS-C: male sex, 109 (59.6%); mean age 7.0 ± 4.7 years; Black race, 56 (30.6%); obesity, 48 (26.2%). Overall, 114 of 183 (62.3%) had evidence of severe acute respiratory syndrome coronavirus 2 infection. All presented with fever, 117 of 183 (63.9%) with gastrointestinal symptoms, and 79 of 183 (43.2%) with shock, which was associated with Black race, higher inflammation, and imaging abnormalities. Twenty-seven patients (14.7%) fulfilled criteria for Kawasaki disease. These patients were younger and had no shock and fewer gastrointestinal, cardiorespiratory, and neurologic symptoms. The remaining 77 patients (49.3%) had mainly fever and inflammation. Inotropic support, mechanical ventilation, and extracorporeal membrane oxygenation were indicated in 72 (39.3%), 43 (23.5%), and 4 (2.2%) patients, respectively. A shorter duration of symptoms before admission was found to be associated with poor patient outcome and for extracorporeal membrane oxygenation and/or death, with 72.3% (95% confidence interval: 0.56-0.90;
= .006) increased risk per day reduction and 63.3% (95% confidence interval: 0.47-0.82;
< .0001) increased risk per day reduction respectively.
In this case series, children with MIS-C presented with a wide clinical spectrum, including Kawasaki disease-like, life-threatening shock and milder forms with mainly fever and inflammation. A shorter duration of symptoms before admission was associated with a worse outcome.
Objective To test for associations between abnormal respiratory ciliary motion (CM) and brain abnormalities in infants with congenital heart disease (CHD) Study design We recruited 35 infants with ...CHD preoperatively and performed nasal tissue biopsy to assess respiratory CM by videomicroscopy. Cranial ultrasound scan and brain magnetic resonance imaging were obtained pre- and/or postoperatively and systematically reviewed for brain abnormalities. Segmentation was used to quantitate cerebrospinal fluid and regional brain volumes. Perinatal and perioperative clinical variables were collected. Results A total of 10 (28.5%) patients with CHD had abnormal CM. Abnormal CM was not associated with brain injury but was correlated with increased extraaxial cerebrospinal fluid volume ( P < .001), delayed brain maturation ( P < .05), and a spectrum of subtle dysplasia including the hippocampus ( P < .0078) and olfactory bulb ( P < .034). Abnormal CM was associated with higher composite dysplasia score ( P < .001), and both were correlated with elevated preoperative serum lactate ( P < .001). Conclusions Abnormal respiratory CM in infants with CHD is associated with a spectrum of brain dysplasia. These findings suggest that ciliary defects may play a role in brain dysplasia in patients with CHD and have the potential to prognosticate neurodevelopmental risks.
Background During the SARS-CoV2 pandemic, there has been increase in hyperinflammatory presentation in previously healthy children with a variety of cardiac manifestations. Our objective is to ...describe the cardiac manifestations found in an international cohort of 55 pediatric cases with multi-system inflammatory syndrome (MIS-C) during the SARS-CoV2 pandemic. Methods and Results We reviewed data on previously healthy pediatric patients (≤18 years) with structurally normal hearts who presented at hospitals in the United States, United Kingdom, Spain and Pakistan with MIS-C and had consultation with a pediatric cardiologist. Data collected included demographics, clinical presentation, laboratory values, electrocardiographic abnormalities, echocardiographic findings and initial therapies. A total of 55 patients presented with MIS-C. Thirty-five patients (64%) had evidence of decreased left ventricular function, 17 (31%) had valvulitis, 12 (22%) with pericardial effusion and 11 (20%) with coronary abnormalities. Twenty-seven (49%) required ICU admission and 24 (44%) had evidence of shock. Eleven patients (20%) fulfilled complete Kawasaki disease criteria and had lower NT pro-BNP, D-dimer and ferritin levels compared with those who did not fulfill criteria. Electrophysiologic abnormalities occurred in 6 patients and included complete atrioventricular (AV) block, transient AV block and ventricular tachycardia. Conclusions We describe the first international cohort of pediatric patients with MIS-C during the SARS-CoV2 pandemic with a range of cardiac manifestations. This paper brings awareness and alertness to the global medical community to recognize these children during the pandemic and understand the need for early cardiology evaluation and follow-up.
Introduction
Right ventricular (RV) dilatation is the determining prognostic factor in the long-term follow up of patients with repaired Tetralogy of Fallot (TOF). The objective of this study is to ...analyze whether the results vary depending on the timing of the complete repair and on the surgical technique applied.
Material–Methods
This is a retrospective longitudinal study in which patients with standard TOF were divided into 3 groups depending on their age at surgical repair: group 1 = Early repair (
n
= 12,1-8 months), group 2 = Late repair (
n
= 26, > 8 months), and group 3 = Late repair with previous palliative surgery (
n
= 17, > 8 months). Clinical, echocardiographic and cardiac magnetic resonance (CMR) data from patients that had received complete reparative surgery in our institution from January 2000 to March 2014 were analyzed and compared.
Results
55 patients with echocardiogram and CMR studies (13.39 ± 3.59 years) were reviewed. All patients had at least moderate pulmonary regurgitation (PR). We observed a positive correlation between PR and right ventricular end-diastolic volume (
r
2
= 0.418;
p
= 0,004). Group 3 had more severe right ventricular dilatation than patients in groups 1 and 2 (
p
= 0.001). No differences in right ventricular end-diastolic volume, PR, and pulmonary trunk dimensions were observed between groups 1 and 2. Patients in group 3 had a longer hospital stay.
Conclusions
Although all patients from our cohort had significant PR, age at surgery was not related to RV or pulmonary trunk dilatation. Previous palliative surgery was associated with more severe right ventricular dilatation and longer hospital stays. No differences were observed between early and late repair groups. Our study suggests that postponing TOF repair to a late stage does not improve the degree of PR or long-term morbidity from RV dilatation. Palliative surgery should be avoided if possible.