Apixaban for Prevention of Thromboembolism in Pediatric Heart Disease.

BACKGROUND: Children with heart disease frequently require anticoagulation for thromboprophylaxis. Current standard of care (SOC), vitamin K antagonists or low-molecular-weight heparin, has significant disadvantages. OBJECTIVES: The authors sought to describe safety, pharmacokinetics (PK), pharmacodynamics, and efficacy of apixaban, an oral, direct factor Xa inhibitor, for prevention of thromboembolism in children with congenital or acquired heart disease. METHODS: Phase 2, open-label trial in children (ages, 28 days to <18 years) with heart disease requiring thromboprophylaxis. Randomization 2:1 apixaban or SOC for 1 year with intention-to-treat analysis. PRIMARY ENDPOINT: a composite of adjudicated major or clinically relevant nonmajor bleeding. Secondary endpoints: PK, pharmacodynamics, quality of life, and exploration of efficacy. RESULTS: From 2017 to 2021, 192 participants were randomized, 129 apixaban and 63 SOC. Diagnoses included single ventricle (74%), Kawasaki disease (14%), and other heart disease (12%). One apixaban participant (0.8%) and 3 with SOC (4.8%) had major or clinically relevant nonmajor bleeding (% difference -4.0 [95% CI: -12.8 to 0.8]). Apixaban incidence rate for all bleeding events was nearly twice the rate of SOC (100.0 vs 58.2 per 100 person-years), driven by 12 participants with ≥4 minor bleeding events. No thromboembolic events or deaths occurred in either arm. Apixaban pediatric PK steady-state exposures were consistent with adult levels. CONCLUSIONS: In this pediatric multinational, randomized trial, bleeding and thromboembolism were infrequent on apixaban and SOC. Apixaban PK data correlated well with adult trials that demonstrated efficacy. These results support the use of apixaban as an alternative to SOC for thromboprophylaxis in pediatric heart disease. (A Study of the Safety and Pharmacokinetics of Apixaban Versus Vitamin K Antagonist [VKA] or Low Molecular Weight Heparin [LMWH] in Pediatric Subjects With Congenital or Acquired Heart Disease Requiring Anticoagulation; NCT02981472).

Balloon Atrial Septostomy in a Premature Infant.

Balloon atrial septostomy (BAS) in premature and very low weight infants has not been described. We present a successful BAS in a 1.4-kg, 13-day-old ex-31 6/7-week infant with dextro-transposition of the great arteries and a restrictive atrial septum. (Level of Difficulty: Advanced.).

Late Outcomes of Transcatheter Coarctation Intervention in Infants with Biventricular Anatomy.

Determine outcomes of catheter intervention for aortic coarctation in infants. Aortic coarctation in infants following surgical repair and in high surgical risk native cases remains a challenging problem. Catheter intervention is an alternative to surgical intervention. Single-center, chart review of infants with biventricular anatomy who underwent coarctation stent placement or balloon angioplasty between 04/2004 and 04/2020. Outcomes of interest included change in aortic lumen diameter, peak gradient, number of re-interventions, time to re-intervention, and adverse events. Thirty-four patients were included in analysis, of those 16 underwent stent placement. Patients' mean age was 4.0 ± 3.0 months and weight of 5.3 ± 1.9 kg. Follow-up interval was 5.4 ± 5.1 years (0.2-16.1 years). Twelve (35%) patients underwent procedure due to ventricular dysfunction; the rest were for high resting gradient. Coarctation diameter increased from 2.4 ± 1.0 to 4.5 ± 1.3 (p < 0.01) and gradient decreased from 32.0 ± 18.4 mmHg to 9.2 ± 8.8 mmHg (p < 0.01). Thirteen (81%) of the stented patients required at least one re-intervention, at an average of 1.7 ± 3.2 years from the index procedure. Five (28%) of those undergoing balloon angioplasty required repeat intervention. There was no mortality due to the procedure and one late mortality. One patient had a serious procedural adverse event. On follow-up, 12 (35%) were on anti-hypertensive medications. Catheter intervention, including stent placement, for aortic coarctation in infants is feasible with an acceptable adverse event profile. Repeat interventions are common.

The incidence of recurrent laryngeal nerve injury resulting in vocal cord paralysis following interventional congenital catheterisation procedures.

BACKGROUND: Recurrent laryngeal nerve injury leading to vocal cord paralysis is a known complication of cardiothoracic surgery. Its occurrence during interventional catheterisation procedures has been documented in case reports, but there have been no studies to determine an incidence. OBJECTIVE: To establish the incidence of left recurrent laryngeal nerve injury leading to vocal cord paralysis after left pulmonary artery stenting, patent ductus arteriosus device closure and the combination of the procedures either consecutively or simultaneously. METHODS: Members of the Congenital Cardiovascular Interventional Study Consortium were asked to perform a retrospective analysis to identify cases of recurrent laryngeal nerve injury after the aforementioned procedures. Twelve institutions participated in the analysis. They also contributed the total number of each procedure performed at their respective institutions for statistical purposes. RESULTS: Of the 1337 patients who underwent left pulmonary artery stent placement, six patients (0.45%) had confirmed vocal cord paralysis. 4001 patients underwent patent ductus arteriosus device closure, and two patients (0.05%) developed left vocal cord paralysis. Patients who underwent both left pulmonary artery stent placement and patent ductus arteriosus device closure had the highest incidence of vocal cord paralysis which occurred in 4 of the 26 patients (15.4%). Overall, 92% of affected patients in our study population had resolution of symptoms. CONCLUSION: Recurrent laryngeal nerve injury is a rare complication of left pulmonary artery stent placement or patent ductus arteriosus device closure. However, the incidence is highest in patients undergoing both procedures either consecutively or simultaneously. Additional research is necessary to determine contributing factors that might reduce the risk of recurrent laryngeal nerve injury.

Postfire nitrogen balance of Mediterranean shrublands: Direct combustion losses versus gaseous and leaching losses from the postfire soil mineral nitrogen flush.

Fire is a major factor controlling global carbon (C) and nitrogen (N) cycling. While direct C and N losses caused by combustion have been comparably well established, important knowledge gaps remain on postfire N losses. Here, we quantified both direct C and N combustion losses as well as postfire gaseous losses (N2 O, NO and N2 ) and N leaching after a high-intensity experimental fire in an old shrubland in central Spain. Combustion losses of C and N were 9.4 Mg C/ha and 129 kg N/ha, respectively, representing 66% and 58% of initial aboveground vegetation and litter stocks. Moreover, fire strongly increased soil mineral N concentrations by several magnitudes to a maximum of 44 kg N/ha 2 months after the fire, with N largely originating from dead soil microbes. Postfire soil emissions increased from 5.4 to 10.1 kg N ha-1  year-1 for N2 , from 1.1 to 1.9 kg N ha-1  year-1 for NO and from 0.05 to 0.2 kg N ha-1  year-1 for N2 O. Maximal leaching losses occurred 2 months after peak soil mineral N concentrations, but remained with 0.1 kg N ha-1  year-1 of minor importance for the postfire N mass balance. 15 N stable isotope labelling revealed that 33% of the mineral N produced by fire was incorporated in stable soil N pools, while the remainder was lost. Overall, our work reveals significant postfire N losses dominated by emissions of N2 that need to be considered when assessing fire effects on ecosystem N cycling and mass balance. We propose indirect N gas emissions factors for the first postfire year, equalling to 7.7% (N2 -N), 2.7% (NO-N) and 5.0% (N2 O-N) of the direct fire combustion losses of the respective N gas species.

Early Cardiac Catheterization Leads to Shortened Pediatric Extracorporeal Membrane Oxygenation Run Duration.

OBJECTIVE: Cardiac catheterization in patients receiving extracorporeal life support (ECLS) has previously been shown to be safe and, in many cases, therapeutic. However, the influence of cardiac catheterization on clinical outcomes in this patient population has not been clearly defined. METHODS: A single institution, retrospective review of all pediatric cardiac ECLS patients who underwent cardiac catheterization between January 2006 and September 2015 was performed. RESULTS: Eighty-two interventional cardiac catheterization procedures were performed on 74 patients. Catheterization findings directly led to catheterization-based or surgical intervention in 54 (73%) patients. One (1.2%) catheterization-related complication occurred (pulmonary artery rupture), which ultimately resulted in death. Patients who underwent early catheterization (≤72 hours of ECLS initiation) required shorter total duration of ECLS than patients who underwent catheterization >72 hours after ECLS initiation (136 hours vs. 227 hours, P < 0.01). The groups experienced similar rates of interventions based on catheterization findings (72% early cath vs. 74% late cath, P = 0.81). Survival to hospital discharge was higher in the early catheterization group (74% vs. 51%, P = 0.04). In multivariate models adjusting for covariates, early catheterization was associated with a reduction in ECLS duration by approximately 150 hours (P < 0.01). CONCLUSIONS: Cardiac catheterization is safe in pediatric ECLS patients and an earlier catheterization is associated with shorter duration of ECLS and improved hospital survival. Diagnostic cardiac catheterization should be considered in patients who remain dependent on ECLS after several days of support.

Long-term outcomes and re-interventions following balloon aortic valvuloplasty in pediatric patients with congenital aortic stenosis: A single-center study.

OBJECTIVES: To describe long-term risk of mortality, aortic insufficiency (AI), and re-intervention following balloon aortic valvuloplasty (BAV) in pediatric patients and to identify risk factors for re-intervention. BACKGROUND: Few studies report long-term outcomes following BAV in infants and children. METHODS: Kaplan-Meier estimates and proportional hazards regression were used in a retrospective study of 154 patients undergoing BAV from 1993 to 2013. RESULTS: Seventy-six (49%) patients were neonates. Aortic stenosis (AS) gradients were reduced by 38 ± 19 mm Hg. Moderate or severe AI developed acutely in 19 (12%) patients. Estimates of fifteen-year transplant-free survival were 85% (95%CI: 73-92%) in neonates, 94% (95%CI: 80-96%) in infants, and 100% in older patients. Neonates had an elevated long-term risk of AI (P < 0.001) and left heart re-interventions (P = 0.02). At 15 years, an estimated 32% (95%CI: 15-50%) of neonates and 44% (95%CI: 20-65%) of non-neonates remained free from re-intervention; an estimated 45% (95% CI: 26-63%) of neonates and 62% (95% CI: 40-77%) of non-neonates remained free of aortic valve replacement (AVR). Neonatal age, additional left heart lesions, higher pre- and post-dilation gradients, and acute AI were associated with LVOT re-interventions. Post-dilation gradient ≥30 mm Hg and acute AI were associated with AVR. Patients with moderate or severe acute AI but a residual AS gradient <30 mm Hg had a greater risk of AVR compared to patients with a residual AS gradient ≥30 mm Hg but mild or less AI (HR: 2.98 [95% CI: 1.01-8.77]). CONCLUSIONS: While post-BAV survival is excellent, long-term risks of AI and re-intervention are significant. Acute AI is a more strongly associated with AVR than residual AS. © 2016 Wiley Periodicals, Inc.

Neoaortic thrombus after Norwood procedure: complication of extracorporeal life support?

Hypoplastic left heart syndrome is the most common diagnosis among infants requiring cardiac extracorporeal life support (ECLS) in the neonatal period, with more than half of patients experiencing an ECLS-related complication. We present a case of nearly obstructing neoaortic thrombus during ECLS occurring in the early postoperative period after modified Norwood palliation of hypoplastic left heart syndrome. Stasis within the neoaortic root due to the increased ventricular afterload associated with venoarterial ECLS may have potentiated this complication. Echocardiographic monitoring and early cardiac catheterization while on ECLS enabled prompt diagnosis and timely surgical correction.

Modified Blalock-Taussig shunt versus ductal stenting for palliation of cardiac lesions with inadequate pulmonary blood flow.

OBJECTIVE: The modified Blalock-Taussig shunt is the most commonly used palliative procedure for infants with ductal-dependent pulmonary circulation. Recently, catheter-based stenting of the ductus arteriosus has been used by some centers to avoid surgical shunt placement. We evaluated the durability and safety of ductal stenting as an alternative to the modified Blalock-Taussig shunt. METHODS: A single-institution, retrospective review of patients undergoing modified Blalock-Taussig shunt versus ductal stenting was performed. Survival, procedural complications, and freedom from reintervention were the primary outcome variables. RESULTS: A total of 42 shunted and 13 stented patients with similar age and weight were identified. Survival to second-stage palliation, definitive repair, or 12 months was similar between the 2 groups (88% vs 85%; P = .742). The incidence of surgical or catheter-based reintervention to maintain adequate pulmonary blood flow was 26% in the shunted patients and 25% in the stented patients (P = 1.000). Three shunted patients (7%) required intervention to address contralateral pulmonary artery stenosis and 3 (7%) required surgical reintervention to address nonpulmonary blood flow-related complications. The need for ipsilateral or juxtaductal pulmonary artery intervention at, or subsequent to, second-stage palliation or definitive repair was similar between the 2 groups. CONCLUSIONS: Freedom from reintervention to maintain adequate pulmonary blood flow was similar between infants undergoing modified Blalock-Taussig shunt or ductal stenting as an initial palliative procedure. However, a greater percentage of shunted patients experienced procedure-related complications and distal branch pulmonary artery stenosis. Palliative ductal stenting appears to be a safe and effective alternative to modified Blalock-Taussig in selected infants.

Bloodstream infections increased after delayed sternal closure: cause or coincidence.

BACKGROUND: Infants who undergo major cardiac operations are at risk for developing bloodstream infections which contribute to the morbidity, mortality, and cost of treatment. Determining what factors are associated with this increased risk of infection may aid in prevention. We sought to evaluate the practice of delayed sternal closure after neonatal cardiac surgery to determine its role as a risk factor for postoperative bloodstream infection. METHODS: We reviewed 110 consecutive patients with hypoplastic left heart syndrome after stage 1 Norwood procedure at Children's Healthcare of Atlanta. The rates of bloodstream infections were determined and risks analyzed with regard to postoperative status of sternal closure; primary versus delayed. RESULTS: Delayed sternal closure was utilized in 67 of 110 patients (61%), while 43 patients had primary sternal closure in the operating room. Overall rate of bloodstream infection was 22% (24 of 110), with 83% (20 of 24) of infections occurring in the delayed closure group. Among infants with delayed closure, 30% developed bloodstream infection, as compared with 9% of patients with primary closure (p = 0.017). Patients with delayed closure had a fourfold increased risk (odds ratio 3.9, p = 0.03) of developing bloodstream infection in-hospital. Predominant organisms were coagulase negative Staphylococcus species; there was one case of mediastinitis. CONCLUSIONS: Delayed sternal closure is associated with an increased likelihood of bloodstream infection and should be recognized as a risk factor after neonatal cardiac operations.

Soil CO2 efflux in a mixed pine-oak forest in Valsaín (central Spain).

Soil-surface CO2 efflux and its spatial and temporal variation were investigated in a southern Mediterranean, mixed pine-oak forest ecosystem on the northern slopes of the Sierra de Guadarrama in Spain from February 2006 to July 2006. Measurements of soil CO2 efflux, soil temperatures, and moisture were conducted in nine 1963-m2 sampling plots distributed in a gradient around the ecotone between Pinus sylvestris L. and Quercus pyrenaica Lam. forest stands. Total soil organic matter, Walkey-Black C, particulate organic matter, organic matter fraction below 53 microm, total soil nitrogen content, total soil organic carbon content, and pH were also measured under three representative mature oak, pine, and mixed pine-oak forest stands. Soil respiration showed a typical seasonal pattern with minimums in winter and summer, and maximums in spring, more pronounced in oak and oak-pine stands. Soil respiration values were highest in pine stands during winter and in oak stands during spring and summer. Soil respiration was highly correlated with soil temperatures in oak and pine-oak stands when soil moisture was above a drought threshold of 15%. Below this threshold value, soil moisture was a good predictor of soil respiration in pine stands. Greater soil organic matter, particulate organic matter, Walkey-Black C, total organic C, and total N content in pine compared to oak sites potentially contributed to the greater total soil CO2 efflux in these stands during the winter. Furthermore, opposing trends in the organic matter fraction below 53 microm and soil respiration between plots suggest that in oak stands, the C forms are less affected by possible changes in use. The effects of soil properties on soil respiration were masked by differences in soil temperature and moisture during the rest of the year. Understanding the spatial and temporal variation even within small geographic areas is essential to assess C budgets at ecosystem level accurately. Thus, this study bears important implications for the study of large-scale ecosystem dynamics, particularly in response to climatic change.