Whole-exome sequencing reveals a monogenic cause in 56% of individuals with laterality disorders and associated congenital heart defects.

BACKGROUND: The molecular basis of heterotaxy and congenital heart malformations associated with disruption of left-right asymmetry is broad and heterogenous, with over 25 genes implicated in its pathogenesis thus far. OBJECTIVE: We sought to elucidate the molecular basis of laterality disorders and associated congenital heart defects in a cohort of 30 unrelated probands of Arab-Muslim descent, using next-generation sequencing techniques. METHODS: Detailed clinical phenotyping followed by whole-exome sequencing (WES) was pursued for each of the probands and their parents (when available). Sanger sequencing was used for segregation analysis of disease-causing mutations in the families. RESULTS: Using WES, we reached a molecular diagnosis for 17 of the 30 probands (56.7%). Genes known to be associated with heterotaxy and/or primary ciliary dyskinesia, in which homozygous pathogenic or likely pathogenic variants were detected, included CFAP53 (CCDC11), CFAP298 (C21orf59), CFAP300, LRRC6, GDF1, DNAAF1, DNAH5, CCDC39, CCDC40, PKD1L1 and TTC25. Additionally, we detected a homozygous disease causing mutation in DAND5, as a novel recessive monogenic cause for heterotaxy in humans. Three additional probands were found to harbour variants of uncertain significance. These included variants in DNAH6, HYDIN, CELSR1 and CFAP46. CONCLUSIONS: Our findings contribute to the current knowledge regarding monogenic causes of heterotaxy and its associated congenital heart defects and underscore the role of next-generation sequencing techniques in the diagnostic workup of such patients, and especially among consanguineous families.

Mutations in PPCS, Encoding Phosphopantothenoylcysteine Synthetase, Cause Autosomal-Recessive Dilated Cardiomyopathy.

Coenzyme A (CoA) is an essential metabolic cofactor used by around 4% of cellular enzymes. Its role is to carry and transfer acetyl and acyl groups to other molecules. Cells can synthesize CoA de novo from vitamin B5 (pantothenate) through five consecutive enzymatic steps. Phosphopantothenoylcysteine synthetase (PPCS) catalyzes the second step of the pathway during which phosphopantothenate reacts with ATP and cysteine to form phosphopantothenoylcysteine. Inborn errors of CoA biosynthesis have been implicated in neurodegeneration with brain iron accumulation (NBIA), a group of rare neurological disorders characterized by accumulation of iron in the basal ganglia and progressive neurodegeneration. Exome sequencing in five individuals from two unrelated families presenting with dilated cardiomyopathy revealed biallelic mutations in PPCS, linking CoA synthesis with a cardiac phenotype. Studies in yeast and fruit flies confirmed the pathogenicity of identified mutations. Biochemical analysis revealed a decrease in CoA levels in fibroblasts of all affected individuals. CoA biosynthesis can occur with pantethine as a source independent from PPCS, suggesting pantethine as targeted treatment for the affected individuals still alive.

Immune and TRG repertoire signature of the thymus in Down syndrome patients.

BACKGROUND: Patients with Down syndrome (DS) are at increased risk for infections and autoimmune disorders. Although several immunological abnormalities were previously found, differences in T cell receptor repertoire have never been shown. Thus we compared the T cell receptor gamma (TRG) repertoire in DS and non-syndromic pediatric patients by next-generation sequencing, in addition to other immunological markers. METHODS: Genomic DNA was extracted from thymuses of pediatric patients who underwent heart surgery, where six were with DS and six were non-syndromic patients. Peripheral blood counts, T cell subpopulations, thymus TCR excision circles (TRECs), spectratyping, and next-generation sequencing for TRG were analyzed. RESULTS: The mean age of the patients was 7 months and the mean lymphocyte count was slightly lower in patients with DS, whereas thymus TREC results were similar to non-syndromic patients (p = 0.197). The TRG repertoire analysis showed that patients with DS had a significantly larger number of unique TRG sequences, together with decreased clonal expansion. Lastly, the V and J gene usages in the thymus were similar in DS and non-syndromic patients. CONCLUSIONS: Patients with DS showed increased TRG repertoire diversity with decreased clonal expansion compared to non-syndromic patients. IMPACT: Alterations in T cell receptor gamma repertoire were found in patients with Down syndrome using next-generation sequencing (NGS) technique. Patients showed increased repertoire diversity and decreased clonal expansion compared to controls. These findings add to previous reports on abnormalities of other immune system components in patients with Down syndrome. NGS technique may point out differences not seen by previous methods. Repertoire abnormalities may contribute to those patients' predisposition to infections and autoimmune diseases.

Protective effect of soluble Klotho in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass support-A pilot study.

OBJECTIVE: The Klotho protein family plays important roles in several metabolic pathways. Soluble Klotho has been recently put forward as an antiaging protein, demonstrating renal and cardiovascular protective traits. Cardiopulmonary bypass (CPB) support during cardiac surgery has been implicated in several adverse outcomes in pediatric and adult patients. Our goal was to assess whether serum Klotho levels can be used to predict outcomes in children undergoing cardiac surgery with CPB due to congenital heart defects (CHDs). METHODS: This prospective study was conducted on pediatric patients admitted to two Pediatric Cardiac Intensive Care Units, between 2012 and 2018. All patients were born with CHD and underwent corrective surgery with CPB. Sequential blood samples were analyzed by enzyme-linked immunosorbent assay for soluble Klotho levels at baseline, 2, 6, and 24 h after surgery. The association between Klotho levels and several demographic, intraoperative, and postoperative clinical and laboratory parameters was studied. RESULTS: Twenty-nine children undergoing cardiac surgery with CPB support were included. Serum Klotho levels were shown to significantly decrease 2 h after surgery and increase to baseline levels after 6 h (p < .001 and p < .05, respectively). Patients with low Klotho levels 2 h after surgery were at a 32-fold higher risk for developing postoperative complications (p = .015, odds ratio < 0.03). Moreover, Klotho levels at each of the four time points were lower in patients who developed postoperative complications. CONCLUSIONS: Cardiac surgery with CPB results in a significant decrease of serum Klotho levels 2 h after surgery in pediatric patients with CHDs, which can be used to predict development of postoperative complications in this patient population.

A founder truncating variant in GDF1 causes autosomal-recessive right isomerism and associated congenital heart defects in multiplex Arab kindreds.

The genetic basis of congenital heart malformations associated with disruption of left-right (L-R) asymmetry is broad and heterogenous, with variants in over 25 genes implicated thus far. Of these, deleterious variants in the Growth/Differentiation Factor 1 (GDF1) gene have been shown to cause heterotaxy with varied complex heart malformations of left-right patterning, in 23 individuals reported to date, either in monoallelic or biallelic state. We report three unrelated individuals exhibiting right isomerism with congenital heart defects, each originating from a consanguineous kindred of Arab-Muslim descent. Using whole exome sequencing, a shared novel homozygous truncating c.608G > A (p.W203*) variant in the GDF1 gene was revealed as the molecular basis of their disease. Subsequently, targeted sequencing of this variant showed full segregation with the disease in these families, with a total of over 15 reportedly affected individuals, enabling genetic counseling, prenatal diagnosis, and planning of future pregnancies. Our findings further confirm the association of biallelic GDF1 variants, heterotaxy and congenital heart defects of left-right patterning, and expand the previously described phenotypic spectrum and mutational profile. Moreover, we suggest targeted screening for the p.W203* variant in relevant clinical circumstances.

MiRNA-208a as a Sensitive Early Biomarker for the Postoperative Course Following Congenital Heart Defect Surgery.

Current clinical risk assessment strategies have poor accuracy for identifying patients who will suffer adverse perioperative events. There is an ongoing need to integrate clinical variables with novel technology and biomarkers to accurately predict outcome after pediatric heart surgery. We tested the hypothesis that miRNAs-208a, -208b, and -499 can serve as noninvasive biomarkers for the extent of myocardial damage and the postoperative clinical course of pediatric patients with congenital heart defects (CHDs) at an early time point following surgery. Serum samples were obtained from 79 pediatric patients before and 6, 12, and 24 h after surgery. MiRNAs-208a, -208b, and -499 were quantified by RQ-PCR. Correlations between the patient's clinical variables and miRNA levels were tested. Our results show that the levels of the three miRNAs were elevated at 6 h after surgery, remained high at 12 h and declined at 24 h after the operation. The amount of all three miRNAs at 6 h after surgery correlated with surgical and laboratory parameters. Their amount at 12 h after surgery correlated with the length of stay at the hospital. Expression levels of miRNA-208a at 6 h were related to the appearance of cardiac complications, and could predict whether a patient will sustain complications or will be ventilated for more than 48 h after surgery. Circulating miRNA-208a is a predictor for the risk of developing cardiac complications during the postoperative course as early as 6 h after heart surgery for CHD in pediatric patients.

Micro-RNA-208a, -208b, and -499 as Biomarkers for Myocardial Damage After Cardiac Surgery in Children.

OBJECTIVES: To test the hypothesis that cardiac-enriched micro-RNAs can serve as accurate biomarkers that reflect myocardial injury and to predict the postoperative course following pediatric cardiac surgery. Micro-RNAs have emerged as plasma biomarkers for many pathologic states. We aimed to quantify preoperative and postoperative plasma levels of cardiac-enriched micro-RNA-208a, -208b, and -499 in children undergoing cardiac surgery and to evaluate correlations between their levels, the extent of myocardial damage, and the postoperative clinical course. DESIGN: PICU. PATIENTS: Thirty pediatric patients that underwent open heart surgery for the correction of congenital heart defects between January 2012 to July 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At 12 hours post surgery, the plasma levels of the micro-RNAs increased by 300- to 4,000-fold. At 24 hours, their levels decreased but remained significantly higher than before surgery. Micro-RNA levels were associated with troponin levels, longer cardiopulmonary bypass and aortic crossclamp times, maximal postoperative aspartate aminotransferase levels, and delayed hospital discharge. CONCLUSIONS: Circulating micro-RNA-208a, -208b, and -499 are detectable in the plasma of children undergoing cardiac surgery and may serve as novel biomarkers for monitoring and forecasting postoperative myocardial injury and recovery.

Catheter-directed thrombolysis for in situ pulmonary artery thrombosis in children.

In situ pulmonary artery thrombosis (ISPAT) is a unique form of pulmonary embolism characterized by local formation of thrombus in the pulmonary arteries. We present here a baby with hypoplastic left heart syndrome who developed ISPAT after Glenn surgery. The patient underwent catheter-directed thrombolysis, followed by systemic anticoagulation with excellent results.

MiRNA-124a: a Potential Biomarker for Neurological Deficits Following Cardiac Surgery in Pediatric Patients.

Brain injury is a major source of patient morbidity after cardiac surgery in children. New early accurate biomarkers are needed for the diagnosis of patients at risk for cerebral postoperative damage. Specific circulating miRNAs have been found as suitable biomarkers for many diseases. We tested whether miRNA-124a reflects neurological injury in pediatric patients following heart surgery. Serum samples were obtained from 34 patients before and six hours after heart surgery. MiRNAs-124a was quantified by RQ-PCR. MiRNA-124a levels six hours after heart surgery correlated with the neurological outcome of the patients. In children with neurological deficits, miRNA-124a levels increased while in those with no neurological deficits the levels decreased. MiRNA-124a was able, at six hours after the operation, to identify patients who are at risk for the appearance of neurological deficits. Circulating miRNA-124a is a potential biomarker for the appearance of neurological deficits in pediatric patients following heart surgery. Graphical Abstract.

Recommendations From the Professional Advisory Committee on Nursing Practice in the Care of ECMO-Supported Patients.

BACKGROUND: By July 2020, the Extracorporeal Life Support Organization had documented more than 133 000 extracorporeal membrane oxygenation (ECMO) implementations, with more than 61 000 implementations in adult patients. No clear policies regarding the authority and responsibility of nursing staff in the treatment of ECMO-supported patients are currently available. OBJECTIVE: To formulate evidence-based recommendations for nursing care of ECMO-supported patients. METHODS: The National Head Nurse's office and the Professional Guidelines Department in the Nursing Division of Israel's Ministry of Health formed the Professional Advisory Committee on Nursing Practice in the Care of ECMO-Supported Patients to address concerns regarding the current state of professional nursing practice in the care of these patients. The Professional Advisory Committee brought together 15 senior Israeli ECMO nursing experts who explored the potential of registered nurses in caring for ECMO-supported patients, considered the competencies of nurses treating ECMO-supported patients, discussed training programs and health care policy, and examined nursing outcomes for quality assurance. RESULTS: The Professional Advisory Committee formulated recommendations regarding the following priority issues: (1) determining boundaries of professional authority and nurses' responsibilities, including designated activities for different professional ranks of registered nurses; (2) providing appropriate content for the training programs offered, such as generic/basic, above-basic, and clinical specialization nursing programs; and (3) defining relevant quality measures for nursing treatment of ECMO-supported patients. CONCLUSIONS: Introducing international standards would ensure the safety and effectiveness of nursing care for ECMO-supported patients through quality and risk management and establishment of new evidence-based nursing practices.

Blood lactate levels differ significantly between surviving and nonsurviving patients within the same risk-adjusted Classification for Congenital Heart Surgery (RACHS-1) group after pediatric cardiac surgery.

This study aimed to examine the association between lactate levels in the first hours after surgery for congenital heart defects and the results of Risk-Adjusted Classification for Congenital Heart Surgery (RACHS-1) scoring and to evaluate serial lactate levels over time to determine whether they can serve as a supplementary tool for postoperative assessment within the same RACHS-1 group of patients. A retrospective cohort study was performed using data retrieved from a clinical database of 255 children who had surgery for congenital heart defects between 1999 and 2001 at Sheba Medical Center. Lactate levels were measured postoperatively four times (mg/dL units). The last sample was taken at the end of the surgical procedure, and lactate levels were measured at admission to the pediatrics critical care unit, then 6 and 12 h after admission. The lactate level was measured via arterial blood gases. A total of 27 deaths occurred, yielding a mortality rate of 7.4% when Norwood operations were excluded and 10.16% when they were included. The mean initial postoperative lactate level was significantly lower for survivors (42.2 ± 32.0 mg/dL) than for nonsurvivors (85.4 ± 54.1 mg/dL) (p < 0.01). The serial mean lactate levels decreased progressively for all surviving patients (r (2) = 0.96) compared with nonsurvivors (r (2) = 0.02). The lactate levels correlated with the RACHS-1 subgroups at each time point (r (2) > 0.96 for all). The Pearson correlations between postoperative lactate levels (last lactate measurement taken in the operating room) and cardiopulmonary bypass (CPB) duration (r = 0.549), clamp duration (r = 0.586), and the inotropic score (r = 0.466) (p < 0.001 for all) were significantly positive. The correlations between the maximum lactate levels (during the first 12 postoperative hours) and CPB duration (r = 0.496), clamp duration (r = 0.509), and the inotropic score (r = 0.633) (p < 0.001 for all) were extremely positive. The early elevation of lactate levels in RACHS-1 subgroups 1 to 3 were highly correlated with poor prognosis and death (p < 0.03). In addition, the lactate levels differed significantly between survivors and nonsurvivors within the same RACHS-1 subgroup. The survivors in RACHS-1 subgroups 1 to 3 had lower mean lactate levels than the nonsurvivors in this group (P = 0.011), and this also held true for the survivors and nonsurvivors in RACHS-1 subgroups 4 to 6 (P = 0.026). Lactate levels differed significantly between survivors and nonsurvivors within the same RACHS-1 subgroup. This combination allows the targeting of appropriately intensive interventions and therapies toward the sickest patients.

Predictors for plication performance following diaphragmatic paralysis in children.

INTRODUCTION AND OBJECTIVES: Diaphragmatic paralysis (DP) in children can result from various etiologies. Guidelines for patient selection for diaphragmatic plication (DPL) are lacking. Our objectives were to describe the etiologies of DP and to determine the risk factors and predictors for DPL in the pediatric population. METHODS: Retrospective data were retrieved from departmental databases on patients with DP from the pediatric, cardiac, and neonatal intensive care departments of Safra Children's Hospital from 2010 to 2017. RESULTS: DP was diagnosed in 88 patients, 29 with noncardiac surgery-related etiologies, for example, congenital, surgery, trauma, and shock and 59 with cardiac surgery-related etiologies. In total, 27 (31%) patients underwent DPL, and they had significant comorbidities involving respiratory, central nervous, and cardiovascular systems, higher lung injury scores, and lower weight compared with the patients who did not undergo DPL (P = .002, P = .002, P < .001, P = .012, and P = .013, respectively). A multivariate regression model revealed significant independent predictors for DPL, including morbidities of central nervous (odds ratio [OR = 9.651, P = .005), respiratory (OR = 4.875, P = .039), and cardiovascular systems (OR = 23.938, P = .001). CONCLUSIONS: Etiologies of DP are very diverse in the pediatric population. Comorbidities of respiratory, central nervous, and cardiovascular systems are risk factors for plication requirement in respiratory support-dependent pediatric patients with DP. Early DPL should be considered in these patients.

Preoperative miRNA-208a as a Predictor of Postoperative Complications in Children with Congenital Heart Disease Undergoing Heart Surgery.

Major perioperative cardiovascular events are important causes of morbidity in pediatric patients with congenital heart disease who undergo reparative surgery. Current preoperative clinical risk assessment strategies have poor accuracy for identifying patients who will sustain adverse events following heart surgery. There is an ongoing need to integrate clinical variables with novel technology and biomarkers to accurately predict outcome following pediatric heart surgery. We tested whether preoperative levels of miRNAs-208a can serve as such a biomarker. Serum samples were obtained from pediatric patients immediately before heart surgery. MiRNA-208a was quantified by RQ-PCR. Correlations between the patient's clinical variables and miRNA levels were tested. Lower levels of preoperative miRNA-208a correlated with and could predict the appearance of postoperative cardiac and inflammatory complications. MiRNA-208a may serve as a biomarker for the prediction of patients who are at risk to develop complications following surgery for the repair of congenital heart defects.

Terlipressin for children with extremely low cardiac output after open heart surgery.

BACKGROUND: Terlipressin, a long-acting analog of vasopressin, has been used successfully in patients with extremely low cardiac output, but its application in children following open heart surgery is limited. OBJECTIVE: To describe our experience using terlipressin in children with extremely low cardiac output after open heart surgery. METHODS: Records were reviewed of all pediatric patients between January 2003 and December 2005 who had undergone open heart surgery, experienced extremely low cardiac output, and were treated with terlipressin as rescue therapy. Mean arterial blood pressure, heart rate, urine output, and lactate and oxygenation index values were retrieved and analyzed when available. RESULTS: Twenty-nine children who were considered gravely ill despite conventional vasoactive agents received terlipressin as rescue therapy, which rapidly yielded significant improvements in all measured hemodynamic and respiratory indices. Mean +/- SD arterial blood pressure increased significantly, from 49 +/- 17 to 57 +/- 16 mm Hg after 10 minutes (p = 0.004) and to 64 +/- 15 mm Hg 24 hours after treatment onset (p = 0.001). Twenty-four hours following terlipressin administration, urine output increased from 1.5 +/- 2.1 to 3.0 +/- 2.3 mL/kg/h (p = 0.001), the oxygenation index decreased from 16.5 +/- 27.9 to 9.5 +/- 16.7 in the survivors (p = 0.023), and the inotropic score decreased from 41.9 +/- 19.9 to 32.6 +/- 18.8 (p = 0.009). CONCLUSIONS: Terlipressin caused significant improvement in hemodynamic, respiratory, and renal indices in children with extremely low cardiac output after open heart surgery. Further controlled studies are needed to confirm the drug's safety and efficacy in this population.

Flexible bronchoscopy and bronchoalveolar lavage in pediatric patients with lung disease.

OBJECTIVE: The use of flexible bronchoscopy (FOB) and bronchoalveolar lavage (BAL) in investigating pediatric patient with airway abnormalities and pulmonary infiltrates are indispensable and are now a routine procedure in many centers. Immunocompromised and cancer patients, especially after bone marrow transplantation, and children who have undergone surgery for congenital heart disease (CHD) are at high risk for pulmonary disease. Our aim was to study the diagnostic rate, safety, and clinical yield of FOB in critically ill pediatric patients. DESIGN: : Retrospective chart review. SETTING: Pediatric intensive care unit in a tertiary university hospital. PATIENTS: Three hundred nineteen children who underwent 335 FOB procedures. The indications for bronchoscopy included infectious agent identification in immune-competent patients with new pulmonary infiltrates seen on chest radiograph (46%) and in patients with fever and neutropenia with respiratory symptoms (18%), airway anatomy evaluation in patients with upper airway obstruction (16%), CHD (15%), and airway trauma (5%). Data were obtained by reviewing the patients' charts, bronchoscopy reports, and laboratory results. MEASUREMENTS AND MAIN RESULTS: The diagnostic rate of FOB procedures was 79%. FOB and BAL resulted in alteration of management (positive clinical yield) in 70 patients (23.9%). A definite infectious organism was identified in 56 patients (17.6%). The clinical yield in patients with cancer or primary immune deficiency (38.7%) was significantly higher compared with patients with CHD (20.4%, p < 0.01) and pneumonia (17%, p < 0.01). Major complications were observed in two procedures (prolonged apnea), and minor complications (transient desaturation, stridor, and minor bleeding) were observed in 45 patients (14%). CONCLUSIONS: FOB and BAL have an important role in the evaluation of airway abnormality and pulmonary infiltrate in pediatric patients, in whom rapid and accurate diagnosis is crucial for survival. We suggest that FOB should be considered as an initial diagnostic tool in those critically ill patients.

The Experiences of Parents of Children Undergoing Surgery for Congenital Heart Defects: A Holistic Model of Care.

The present article is based on a qualitative study focusing on parents of children born with congenital heart defects (CHDs) and hospitalized in the children's intensive care unit post-surgery. Our aim was to explore parents' subjective experiences as primary caregivers. Ten semi-structured interviews were conducted and analyzed using interpretative phenomenological analysis according to the instructions of Smith and Osborn. Our analysis yielded eight categories which were grouped into four themes and two main superordinate themes: (1) dialectical tension between positive and negative experiences; and (2) fluctuations between the inner and the outer world. The two superordinate themes intersect such that parents report positive as well as negative experiences within both their inner and outer worlds. Based on our analysis, we found that the experience of having a child undergo surgery for a CHD can be regarded as a chaotic period characterized by uncertainty, confusion, and helplessness. It is therefore no surprise that many parents display negative psychological outcomes which extend beyond the period of hospitalization and may also affect their future parenting and coping. However, within this chaotic and stressful situation, parents had occasional supportive experiences which decreased their emotional distress and isolation and helped them throughout this difficult period. We thus conclude that the support offered to parents during the hospitalization period should be increased by trying to minimize their negative experiences and strengthen their inner coping abilities. These changes cannot be implemented without also addressing the needs of the medical staff in their role as caregivers. Therefore, we propose a holistic model of care which supports both parents as caregivers of children undergoing surgery for CHD and the medical staff involved in their care.

Transfusion-related acute hepatic injury following postoperative platelets administration in pediatric patients undergoing the Fontan procedure.

OBJECTIVE: The final common pathway of single ventricle patients is the Fontan procedure. Among the immediate postoperative complications is acute hepatic injury presented by marked elevation of liver enzymes (alanine transaminase [ALT] and aspartate transaminase [AST]). We aimed to determine the contribution of blood products transfusion to acute hepatic injury. DESIGN: Single center retrospective cohort study. SETTING: Pediatric Cardiac Intensive Care Unit at a tertiary medical center. PATIENTS: Ninety-nine pediatric patients undergoing the Fontan procedure between January 2009 and December 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of the four types of blood products, transfusion of platelets was found to significantly affect postoperative levels of ALT and AST. Additional factors included postoperative administration of sodium bicarbonate, decreased flow through the Fontan canal and decreased urine output. Preoperative pulmonary artery pressure and pulmonary vascular resistance, cardiopulmonary bypass time, aortic cross-clamp time, amount of postoperative bleeding, and vasoactive-inotropic score did not influence liver enzymes levels CONCLUSIONS: In pediatric Fontan patients, platelets transfusions contribute to an acute hepatic injury. The relation between platelets and transfusion-related acute lung injury (TRALI) has been well described, but this is the first time it is being described in regard to acute hepatic injury (TRAHI). Changing platelet transfusion strategy could decrease morbidity in Fontan patients but further research is needed.

Heparin-induced thrombocytopenia complicating children after the Fontan procedure: Single-center experience and review of the literature.

Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of heparin therapy. The risk for HIT correlates with the cumulative dosage of heparin exposure. In Fontan patients, recurrent systemic anticoagulation, traditionally with heparin, is used to alleviate the thrombotic complications that may occur postoperatively when the venous pressure rises and the systemic venous flow into the pulmonary arteries becomes sluggish, putting them at increased risk. As a pressure gradient-dependent circulation, elevation in systemic venous pressure, most often by venous thrombosis, contributes to circuit failure. Therefore, when HIT complicates patients after the Fontan procedure, it is associated with a high thrombotic morbidity and mortality; thus, a high index of suspicion is mandatory, based on the clinical signs of HIT. It is crucial to intervene early with alternative anticoagulants when HIT is suspected as this step may improve outcome in these patients.

Circulating MicroRNAs: a Potential Biomarker for Cardiac Damage, Inflammatory Response, and Left Ventricular Function Recovery in Pediatric Viral Myocarditis.

Viral myocarditis (VM) can be a life-threatening event resulting in cardiac failure, chronic cardiomyopathy, and death. VM typically includes three phases, i.e., acute, subacute, and resolution/chronic. We prospectively investigated cardiac- and inflammatory-associated plasma-circulating miRNA levels in eight pediatric patients with VM during the three stages of the disease. The level of cardiac-associated miR-208a was significantly elevated during the acute phase compared with the subacute and resolution/chronic phases. The level of cardiac- and inflammatory-associated miR-21 was significantly elevated during the acute phase compared to the resolution/chronic phase. Moreover, cardiac-associated miR-208b levels during the subacute phase correlated with systolic left ventricular function recovery as measured during the resolution/chronic phase. The findings of our study demonstrate an association between cardiac damage and the inflammatory response and the expression of miR-208a and miR-21 during the pathological progression of myocarditis. We also found that miR-208b levels exhibit a prognostic significance for left ventricular functional recovery.