Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.

BACKGROUND: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD). METHODS: Children with HF attributable to LVSD were randomized to sacubitril/valsartan versus enalapril to assess the efficacy and safety of sacubitril/valsartan at 52 weeks of follow-up. The primary end point of the study was to determine whether sacubitril/valsartan was superior to enalapril for the treatment of pediatric patients with HF attributable to systemic LVSD, assessed using a primary global rank end point consisting of ranking patients from worst to best on the basis of clinical events such as death, listing for urgent heart transplant, mechanical life support requirement, worsening HF, New York Heart Association (NYHA)/Ross class, Patient Global Impression of Severity (PGIS), and Pediatric Quality of Life Inventory physical functioning domain. The change from baseline to 52 weeks in NT-proBNP (N-terminal pro-B-type natriuretic peptide) was an exploratory end point. RESULTS: A total of 375 children (mean age, 8.1±5.6 years; 52% female) were randomized to sacubitril/valsartan (n=187) or enalapril (n=188). At week 52, no significant difference was observed between the 2 treatment arms in the global rank end point (Mann-Whitney probability, 0.52 [95% CI, 0.47-0.58]; Mann-Whitney odds, 0.91 [95% CI, 0.72-1.14]; P=0.42). At week 52, clinically meaningful reductions were observed in both treatment arms in NYHA/Ross, PGIS, Patient Global Impression of Change, and NT-proBNP, without significant differences between groups. Adverse events were similar between treatment arms (incidence: sacubitril/valsartan, 88.8%; enalapril, 87.8%), and the safety profile of sacubitril/valsartan was acceptable in children. CONCLUSIONS: In this study, sacubitril/valsartan did not show superiority over enalapril in the treatment of children with HF attributable to systemic LVSD using the prespecified global rank end point. However, both treatment arms showed clinically meaningful improvements over 52 weeks. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02678312.

Echocardiographic Markers of Mild Pulmonary Hypertension are not Correlated with Worse Respiratory Outcomes in Infants with Bronchiolitis.

Pulmonary hypertension has been reported as a crucial factor in the pathophysiology of severe bronchiolitis. The aim of this study was to evaluate pulmonary artery pressure (PAP) in patients with bronchiolitis and to analyze their correlation with clinical outcomes. This prospective cohort study examined children admitted for bronchiolitis. PAP was assessed by right ventricle (RV) acceleration/ejection time ratio (AT/ET), isovolumic relaxation time, eccentricity index, and the presence of a pulmonary systolic notch. Pulmonary hypertension (PH) was considered if at least two altered parameters were present. Severity of clinical course was established by higher N-terminal (NT)-prohormone BNP (NT-proBNP) values, the need for positive pressure respiratory support (PPRS), and the duration of hospital admission. One hundred sixty-nine children were included in analysis. Sixty-eight patients (40%) required PPRS, and those patients had increased NT-proBNP values and worse tricuspid annular systolic excursion (TAPSE) compared to mild cases (p < 0.001and p < 0.001, respectively). Twenty-two (13%) cases had at least two altered parameters of PAP and met criteria for presumed PH, with no differences in NT-proBNP values, TAPSE, need for PPRS or hospital length of stay compared to normal PAP group (p = 0.98, p = 0.07, p = 0.94 and p = 0.64, respectively). We found no correlation between altered RV AT/ET and worse cardiac function, NT-proBNP values or hospital length of stay. In our cohort, the presence of echocardiographic findings of PH were not associated with worse clinical outcomes. Patients with severe bronchiolitis had higher values ​​of NT-proBNP but, interestingly, no clear association with PH.

Mid-aortic Syndrome in a Pediatric Cohort.

Mid-aortic syndrome (MAS) is an uncommon condition characterized by severe narrowing of the abdominal aorta, usually involving visceral and renal arteries. Most patients are asymptomatic and typically present with incidental hypertension which might evolve into end-organ damage if untreated. Our aim was to review 8 new pediatric MAS cases. A retrospective observational study of all pediatric patients with MAS diagnosis (April 1992-November 2021) was conducted. Patients underwent systematic evaluation (medical and family history; 12-lead electrocardiogram; echocardiogram; angiography and/or computed tomography or magnetic resonance angiography). 8 pediatric patients with MAS were included. Median age at diagnosis was 2.6 [0.2-4.7] years; median follow-up time was 8.6 [6.6-10.0] years. 6/8 patients presented with incidental hypertension, 1/8 with heart murmur, and 1/8 with heart failure symptoms. All patients were on antihypertensive treatment. 1/8 patients underwent surgery and 7/8 an endovascular treatment. At the end of the study period, among the 6 patients that underwent a successful endovascular procedure, 2 achieved good blood pressure (BP) control, 2 acceptable BP control, 1 stage 1 hypertension and, another, stage 2 hypertension. There was 1 death during follow-up. BP monitoring in pediatric patients is crucial for early recognition of MAS. Treatment should be based on the individual clinical characteristics of patients with careful planning of surgical revascularisation, if possible, after adult growth is completed. Our study demonstrates that endovascular treatment might be a good alternative to surgery. Nevertheless, further trials with larger sample size and longer-term follow-up are required to determine the best treatment approach.

Acute Cardiovascular Manifestations in 286 Children With Multisystem Inflammatory Syndrome Associated With COVID-19 Infection in Europe.

BACKGROUND: The aim of the study was to document cardiovascular clinical findings, cardiac imaging, and laboratory markers in children presenting with the novel multisystem inflammatory syndrome associated with coronavirus disease 2019 (COVID-19) infection. METHODS: This real-time internet-based survey has been endorsed by the Association for European Paediatric and Congenital Cardiologists Working Groups for Cardiac Imaging and Cardiovascular Intensive Care. Children 0 to 18 years of age admitted to a hospital between February 1 and June 6, 2020, with a diagnosis of an inflammatory syndrome and acute cardiovascular complications were included. RESULTS: A total of 286 children from 55 centers in 17 European countries were included. The median age was 8.4 years (interquartile range, 3.8-12.4 years) and 67% were boys. The most common cardiovascular complications were shock, cardiac arrhythmias, pericardial effusion, and coronary artery dilatation. Reduced left ventricular ejection fraction was present in over half of the patients, and a vast majority of children had raised cardiac troponin when checked. The biochemical markers of inflammation were raised in most patients on admission: elevated C-reactive protein, serum ferritin, procalcitonin, N-terminal pro B-type natriuretic peptide, interleukin-6 level, and D-dimers. There was a statistically significant correlation between degree of elevation in cardiac and biochemical parameters and the need for intensive care support (P<0.05). Polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 was positive in 33.6%, whereas immunoglobulin M and immunoglobulin G antibodies were positive in 15.7% cases and immunoglobulin G in 43.6% cases, respectively, when checked. One child in the study cohort died. CONCLUSIONS: Cardiac involvement is common in children with multisystem inflammatory syndrome associated with the Covid-19 pandemic. The majority of children have significantly raised levels of N-terminal pro B-type natriuretic peptide, ferritin, D-dimers, and cardiac troponin in addition to high C-reactive protein and procalcitonin levels. In comparison with adults with COVID-19, mortality in children with multisystem inflammatory syndrome associated with COVID-19 is uncommon despite multisystem involvement, very elevated inflammatory markers, and the need for intensive care support.

Role of a Pediatric Cardiologist in the COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) has affected patients across all age groups, with a wide range of illness severity from asymptomatic carriers to severe multi-organ dysfunction and death. Although early reports have shown that younger age groups experience less severe disease than older adults, our understanding of this phenomenon is in continuous evolution. Recently, a severe multisystem inflammatory syndrome in children (MIS-C), with active or recent COVID-19 infection, has been increasingly reported. Children with MIS-C may demonstrate signs and symptoms of Kawasaki disease, but also have some distinct differences. These children have more frequent and severe gastrointestinal symptoms and are more likely to present with a shock-like presentation. Moreover, they often present with cardiovascular involvement including myocardial dysfunction, valvulitis, and coronary artery dilation or aneurysms. Here, we present a review of the literature and summary of our current understanding of cardiovascular involvement in children with COVID-19 or MIS-C and identifying the role of a pediatric cardiologist in caring for these patients.

International evidence-based guidelines on Point of Care Ultrasound (POCUS) for critically ill neonates and children issued by the POCUS Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC).

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Neonatal Non-compacted Cardiomyopathy: Predictors of Poor Outcome.

Non-compacted cardiomyopathy (NCM) is a heterogenous myocardial disorder. Although much has been published in recent years, little is known about NCM in the neonatal period. The objective of this study is to characterize the involvement of newborns affected with NCM and to identify risk factors associated with increased mortality. This is a retrospective study including all neonates diagnosed with NCM between 2006 and 2018. Diagnosis was based on echocardiographic findings. Data were collected regarding prenatal history, gestational age and weight at birth, gender, age at diagnosis, left or biventricular involvement and associated malformations, medical and surgical treatments, and evolution. Fourteen patients were included. The median follow-up duration was 34 months (range 1-87 months). The left ventricular apex and lateral wall were involved in all cases (100%). Thirteen patients (92.8%) had other associated heart malformations. Six patients (42.8%) died during the follow-up period. Patients who had biventricular involvement and poor ventricular function presented a higher risk of death. The main cause of death was ventricular dysfunction (5/6 [83.3%]). During follow-up, eight patients (57.1%) underwent surgery for their cardiac malformations, without higher mortality. NCM must be included in the differential diagnosis of neonatal cardiomyopathy. The higher mortality observed in our series is related not only to the high association with congenital heart disease, but also to a greater presence of early and severe left ventricular dysfunction. We did not find that patients who underwent surgery with cardiopulmonary bypass had worse outcomes.

Comprehensive Functional Echocardiographic Assessment of Transposition of the Great Arteries: From Fetus to Newborn.

To improve the understanding of the pathophysiology of transposition of the great arteries with intact ventricular septum (TGA/IVS) and the cardiac remodeling occurring from fetal to neonatal life, we performed a morphometric and functional echocardiographic assessment in fetuses and newborns. This was a prospective case-control study performed in a tertiary referral center, which included fetuses and newborns with a diagnosis of TGA/IVS between 2011 and 2018. Morphometry and systolic and diastolic function parameters were compared with age and body surface-matched healthy controls. Twenty-one TGA/IVS patients were included during the study period and morphometric and functional echocardiographic data were recorded. TGA/IVS patients showed morphometric and functional changes of increased overall volume and output, predominantly in the aortic component from fetus to newborn, probably due to compensatory mechanisms secondary to brain hypoxia.

Associations of Perioperative Renal Oximetry Via Near-Infrared Spectroscopy, Urinary Biomarkers, and Postoperative Acute Kidney Injury in Infants After Congenital Heart Surgery: Should Creatinine Continue to Be the Gold Standard?

OBJECTIVES: Examine the relationship between perioperative renal regional tissue oximetry, urinary biomarkers, and acute kidney injury in infants after congenital cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, observational. SETTING: Cardiac operating room and cardiac ICU. PATIENTS: Neonates and infants without history of kidney injury or anatomic renal abnormality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Renal regional tissue oximetry was measured intraoperatively and for 48 hours postoperatively. Urinary levels of neutrophil gelatinase-associated lipocalin and tissue inhibitor of metalloproteinases 2 together with insulin-like growth factor-binding protein 7 were measured preoperatively, 2, 12, and 24 hours postoperatively. Patients were categorized as no acute kidney injury, stage 1, or Stage 2-3 acute kidney injury using the Kidney Disease: Improving Global Outcomes criteria with 43 of 70 (61%) meeting criteria for any stage acute kidney injury. Stage 2-3 acute kidney injury patients had higher tissue inhibitor of metalloproteinases 2, insulin-like growth factor-binding protein 7 at 2 hours (0.3 vs 0.14 for stage 1 acute kidney injury and 0.05 for no acute kidney injury; p = 0.052) and 24 hours postoperatively (1.71 vs 0.27 for stage 1 acute kidney injury and 0.19 for no acute kidney injury, p = 0.027) and higher neutrophil gelatinase-associated lipocalin levels at 24 hours postoperatively (10.3 vs 3.4 for stage 1 acute kidney injury and 6.2 for no acute kidney injury, p = 0.019). Stage 2-3 acute kidney injury patients had lower mean cardiac ICU renal regional tissue oximetry (66% vs 79% for stage 1 acute kidney injury and 84% for no acute kidney injury, p = 0.038). Regression analyses showed that tissue inhibitor of metalloproteinases 2, insulin-like growth factor-binding protein 7 at 2 hours postoperatively and nadir intraoperative renal regional tissue oximetry to be independent predictors of postoperative kidney damage as measured by urinary neutrophil gelatinase-associated lipocalin. CONCLUSIONS: We observed modest differences in perioperative renal regional tissue oximetry and urinary biomarker levels compared between acute kidney injury groups classified by creatinine-dependent Kidney Disease: Improving Global Outcomes criteria, but there were significant correlations between renal regional tissue oximetry, tissue inhibitor of metalloproteinases 2, insulin-like growth factor-binding protein 7, and postoperative neutrophil gelatinase-associated lipocalin levels. Kidney injury after infant cardiac surgery may be undetectable by functional assessment (creatinine) alone, and continuous monitoring of renal regional tissue oximetry may be more sensitive to important subclinical acute kidney injury.

Survival and Long-Term Functional Outcomes for Children With Cardiac Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation.

OBJECTIVES: To identify patient- and disease-related factors related to survival and favorable outcomes for children who underwent extracorporeal cardiopulmonary resuscitation after a refractory cardiac arrest. DESIGN: Retrospective observational study with prospective assessment of long-term functional outcome. PATIENTS: Fifty-six consecutive children undergoing extracorporeal cardiopulmonary resuscitation at our institution from 2007 to 2015. Median age at arrest was 3.5 months (interquartile range, 1-53). SETTING: Tertiary pediatric university hospital with a referral heart center. INTERVENTIONS: Health-related quality of life and family functioning assessment with the Pediatric Quality of Life Inventory and the McMaster Family Assessment Device. MEASUREMENTS AND MAIN RESULTS: Fifty-eight consecutive extracorporeal cardiopulmonary resuscitation episodes were included, with 46 (79.3%) related to primary cardiac conditions. Initial cannulation site was central in 19 (32.8%) and peripheral in 39 (67.2%). Survival to decannulation was 77.6% with survival at hospital discharge and at the end of the follow-up period being 65.5% and 62.1%, respectively. Time to follow-up was 38 months (interquartile range, 19-52). Patients who survived tended to be younger (3.5 mo [1 mo to 2 yr] vs 7 mo [1.25 mo to 17 yr]; p = 0.3) with decreased extracorporeal cardiopulmonary resuscitation times (28 min [15-47 min] vs 37.5 min [28.5-55 min]; p = 0.04). Those who received therapeutic hypothermia tended to have higher hospital survival (21/28 [75%] vs 16/29 [55%]; p = 0.08). Follow-up assessments of survivors demonstrated good quality of life and family functioning (Pediatric Quality of Life Inventory, 84 [76-89.5]; McMaster Family Assessment Device, 1.62 [1.33-1.83]). CONCLUSIONS: In this series, extracorporeal cardiopulmonary resuscitation was associated with relatively high survival rates and a good health-related quality of life and family functioning. Larger series are needed to assess whether this technique should be more broadly available in the pediatric critical care community.

Bedside Ultrasound for the Diagnosis of Abnormal Diaphragmatic Motion in Children After Heart Surgery.

OBJECTIVE: To assess the utility of bedside ultrasound combining B- and M-mode in the diagnosis of abnormal diaphragmatic motion in children after heart surgery. DESIGN: Prospective post hoc blinded comparison of ultrasound performed by two different intensivists and fluoroscopy results with electromyography. SETTING: Tertiary university hospital. SUBJECTS: Children with suspected abnormal diaphragmatic motion after heart surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Abnormal diaphragmatic motion was suspected in 26 children. Electromyography confirmed the diagnosis in 20 of 24 children (83.3%). The overall occurrence rate of abnormal diaphragmatic motion during the study period was 7.5%. Median patient age was 5 months (range, 16 d to 14 yr). Sensitivity and specificity of chest ultrasound performed at the bedside by the two intensivists (91% and 92% and 92% and 95%, respectively) were higher than those obtained by fluoroscopy (87% and 83%). Interobserver agreement (k) between both intensivists was 0.957 (95% CI, 0.87-100). CONCLUSIONS: Chest ultrasound performed by intensivists is a valid tool for the diagnosis of diaphragmatic paralysis, presenting greater sensitivity and specificity than fluoroscopy. Chest ultrasound should be routinely used after pediatric heart surgery given its reliability, reproducibility, availability, and safety.

Advanced Low-Cost Ultrasound-Guided Vascular Access Simulation: The Chicken Breast Model.

There is a growing body of literature that supports the use of ultrasound for vascular access. Advanced simulation has become a widely applied technique for training medical staff in vascular access. Nevertheless, advanced simulators are expensive and of limited usage. We describe both a step-wise systematic approach and an experimental cadaveric model of vascular access using a simple piece of chicken that can be easily used for trainees.

Brain Dysplasia Associated with Ciliary Dysfunction in Infants with Congenital Heart Disease.

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.

Early Initiation of Renal Replacement Therapy in Pediatric Heart Surgery Is Associated with Lower Mortality.

Acute kidney injury (AKI) is frequent in the postoperative period of pediatric heart surgery and leads to significant morbidity and mortality. Renal replacement therapies (RRTs) are often used to treat AKI; however, these therapies have also been associated with higher mortality rates. Earlier initiation of RRT might improve outcomes. This study aims to investigate the relationship between the RRT and morbidity and mortality after pediatric heart surgery. We performed a single-center retrospective study of all children undergoing pediatric heart surgery between April 2010 and December 2012 at a tertiary children's hospital. A total of 480 patients were included. Of those, 109 (23 %) were neonates and 126 patients (26 %) developed AKI within the first 72 postoperative hours. Patients who developed AKI had longer PICU admissions [12 days (4-37.75) vs. 4 (2-11); p < 0.001] and hospital length of stay [27 (11-53) vs. 14 (8-24) p < 0.001] and higher mortality [22/126 (17.5 %) vs. 13/354 (3.7 %); p < 0.001]. RRT techniques were used in 32 (6.6 %) patients [18/109 (16 %) neonates and 14/371 (3.8 %) infants and children; p < 0.01], with 25 (78 %) receiving peritoneal dialysis (PD) and 7 (22 %) continuous RRT (CRRT). Patients who received PD within the first 24 postoperative hours had lower mortality compared with those in whom PD was initiated later [4/16 (25 %) vs. 4/9 (44.4 %)]. Mortality among patients who received CRRT was 28.6 % (2/7). No deaths were reported in patients treated with CRRT within the first 24 postoperative hours. Postoperative AKI is associated with higher mortality in children undergoing cardiac surgery. Early initiation of RRT, both PD in neonates and CRRT in pediatric patients, might improve morbidity and mortality associated with AKI.

Teaching Chest Ultrasound in an Experimental Porcine Model.

OBJECTIVE: The objective of this study was to evaluate the efficacy of a short hands-on chest ultrasound course to detect normal lung pattern, pneumothorax (PTX), and pleural effusion (PE) in a porcine animal model. METHODS: Thirty-six trainees with no previous experience in chest ultrasound participated in the study. A 1.5-hour training course covering both theory and practice was developed. All static and dynamic signs of the normal lung parenchyma, PTX, and PE were analyzed. Four pigs were used. Approval by the local institutional animal care was obtained. An 8F drainage catheter was inserted into the pleural cavity under general anesthesia for injection of air or saline solution. A Vivid Q ultrasound with a 12L-RS linear probe was used. A baseline preintervention evaluation and 2 postintervention evaluations (one after theoretical class and the other after additional training with the animal model) were made. Sensitivity and specificity with the 95% confidence interval for recognition of the 3 patterns were analyzed, and results were compared with those obtained in the preintervention evaluation. RESULTS: All normal lung signs were detected, as these were signs of PE and PTX. Participants were able to diagnose a normal pattern (sensitivity, 100% [90%-100%]; specificity, 90% [84%-95%]), PE (sensitivity, 89% [75%-95%]; specificity, 95% [89%-98%]), and PTX (sensitivity, 82% [72%-89%]; specificity, 97% [90%-99%]) after 30 minutes of class and normal pattern (sensitivity, 95% [85%-98%]; specificity, 95% [85%-98%]), PE (sensitivity, 100% [88%-100%]; specificity, 98% [94%-99%]), and PTX (sensitivity, 90% [73%-96%]; specificity, 98% [92%-99%]) in the animal model. CONCLUSIONS: The porcine model is useful for ultrasound examination of the lung parenchyma and detection of pleural disease. Its use in the experimental laboratory is a major refinement that enables trainees to identify acute pulmonary complications.

Impact of the implementation of an interdisciplinary infection control program to prevent surgical wound infection in pediatric heart surgery.

UNLABELLED: Surgical site infection (SSI) remains a major source of morbidity, mortality, and increased health care costs in children undergoing heart surgery. The aim of this study was to assess the effectiveness of an intervention program designed to reduce the high incidence of SSI observed at our center in pediatric patients. An interdisciplinary infection control program including pre-, intra-, and postoperative measures was introduced for children undergoing heart surgery with cardiopulmonary bypass. We conducted a quasi-experimental interventional study comparing a pre-intervention cohort (June 2009 to March 2010) and a post-intervention cohort (July 2011 to July 2012). A significant drop in SSI incidence from 10.9 % (95 % CI 4.7-18.8) to 1.92 % (95 % CI 0.4-5.52) was observed. Variables significantly associated with infection risk were median age (14 days in infected vs 2.3 years in non-infected patients; p<0.01), hospitalization unit (10.3 % SSI cumulative incidence in the neonatal intensive care unit vs 0 cases in the pediatric intensive care unit; p<0.01), and median preoperative hospital stay (14 days in infected vs 1 day in non-infected patients; p=0.03). CONCLUSIONS: The implementation of a new intervention program was associated with an 82 % (95 % CI 34-94) reduction in SSI incidence in children undergoing heart surgery at our center. WHAT IS KNOWN: • Surgical site infection (SSI) is associated with significant morbidity and mortality following pediatric cardiac surgery. • Younger patients and longer cardiopulmonary bypass times are associated with higher SSI rates. What is New: • Comprehensive infection control program including preoperative, intraoperative and postoperative nonpharmacologic measures is a key factor for the prevention of SSI. • A significant reduction in SSI rates can be achieve despite a narrower-spectrum antibiotic usage.

Maternal and foetal angiogenic imbalance in congenital heart defects.

AIMS: 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. METHODS AND RESULTS: 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). CONCLUSION: 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.

Cerebral regional oxygen saturation and serum neuromarkers for the prediction of adverse neurologic outcome in pediatric cardiac surgery.

BACKGROUND: The aim of this study is to determine the utility of non-invasive bedside neuromonitoring, including cerebral regional oxygen saturation (rSO2) measured by near-infrared spectroscopy and serum biomarkers, in identifying children at risk from adverse neurological outcome after heart surgery. METHODS: Prospective observational study including 39 consecutive children undergoing heart surgery with cardiopulmonary bypass (CPB) and normal neurologic exam prior to surgery. Cerebral rSO2 was measured at baseline (prior to surgery) and then continuously during surgery and for the first 16 h post-operatively. Neuromarkers [neuron-specific enolase (NSE), S100ß, glial fibrillary acidic protein (GFAP), and brain-derived neurotrophic factor (BDNF)] were measured in serum at baseline, immediately after CPB and at 16 h post-operatively. Adverse neurological outcome was defined as an abnormal pediatric cerebral performance category (PCPC) scale score at 12 months after surgery. RESULTS: Sixteen children (41 %) had an abnormal PCPC scale score at the 12-month evaluation after surgery. In children with unfavorable neurological outcomes, mean cerebral rSO2 values were lower and the area-under-the-curve below a threshold of 40 and 20% below baseline were also increased. No significant differences were found in serum neuromarkers between groups at the time points that were assessed. CONCLUSIONS: Bedside determination of cerebral rSO2 may have some utility in identifying children at risk for adverse neurological outcome after heart surgery in children. Additional studies that are sufficiently powered to control for the many covariates in this patient population will be required to fully interrogate this important question. The role of serum neuromarkers in the immediate post-operative period do not appear to be helpful in this question, though more thorough interrogation of delayed periods may ultimately demonstrate some utility in answering this question.

Neurodevelopmental outcomes in congenital heart disease: Usefulness of biomarkers of brain injury.

INTRODUCTION: At present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes. METHODS: Prospective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: (1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; (2) clinical and laboratory data from the immediate postnatal and perioperative periods; (3) treatments and complications; (4) neurodevelopment (Bayley-III scale) at age 2 years. RESULTS: the study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores. CONCLUSIONS: children with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years. Studies with larger samples and longer follow-ups are needed to define the role of these biomarkers of brain injury in the prediction of neurodevelopmental outcomes in patients who undergo surgery for management of CHD.