Mental Health Care for Children with Heart Disease and Their Families: Practical Approaches and Considerations for the Pediatric and Pediatric Cardiology Clinician.

Mental health conditions are a common comorbidity among children living with heart disease. Children with congenital heart disease are more likely to have a mental health condition than their unaffected peers or peers with other chronic illnesses, and mental health risk persists across their lifetime. While poorer mental health in adults with congenital heart disease is associated with worse overall health outcomes, the association between mental health and cardiac outcomes for children with heart disease remains unknown. Despite this, it is suspected that mental health conditions go undiagnosed in children with heart disease and that many affected children and adolescents do not receive optimal mental health care. In this article, we review mental health in congenital heart disease across the lifespan, across domains of care, and across diagnoses. Further directions to support mental health care for children and adolescents with heart disease include practical screening and access to timely referral and mental health resources.

Intracardiac echocardiography in paediatric and congenital cardiac ablation shortens procedure duration and improves success without complications.

AIMS: Common to adult electrophysiology studies (EPSs), intracardiac echocardiography (ICE) use in paediatric and congenital heart disease (CHD) EPS is limited. The purpose of this study was to assess the efficacy of ICE use and incidence of associated complications in paediatric and CHD EPS. METHODS AND RESULTS: This single-centre retrospective matched cohort study reviewed EPS between 2013 and 2022. Demographics, CHD type, and EPS data were collected. Intracardiac echocardiography cases were matched 1:1 to no ICE controls to assess differences in complications, ablation success, fluoroscopy exposure, procedure duration, and arrhythmia recurrence. Cases and controls with preceding EPS within 5 years were excluded. Intracardiac echocardiography cases without an appropriate match were excluded from comparative analyses but included in the descriptive cohort. We performed univariable and multivariable logistic regression to assess associations between variables and outcomes. A total of 335 EPS were reviewed, with ICE used in 196. The median age of ICE cases was 15 [interquartile range (IQR) 12-17; range 3-47] years, and median weight 57 [IQR 45-71; range 15-134] kg. There were no ICE-related acute or post-procedural complications. There were 139 ICE cases matched to no ICE controls. Baseline demographics and anthropometrics were similar between cases and controls. Fluoroscopy exposure (P = 0.02), procedure duration (P = 0.01), and arrhythmia recurrence (P = 0.01) were significantly lower in ICE cases. CONCLUSION: Intracardiac echocardiography in paediatric and CHD ablations is safe and reduces procedure duration, fluoroscopy exposure, and arrhythmia recurrence. However, not every arrhythmia substrate requires ICE use. Thoughtful selection will ensure the judicious and strategic application of ICE to enhance outcomes.

Multicenter retrospective evaluation of magnetic resonance imaging in pediatric and congenital heart disease patients with cardiac implantable electronic devices.

BACKGROUND: Guidelines addressing magnetic resonance imaging (MRI) in patients with cardiac implantable electronic devices (CIEDs) provide algorithms for imaging pediatric and congenital heart disease (CHD) patients. Guideline acceptance varies by institution. Guidelines also do not support routine MRI scans in patients with epicardial or abandoned leads, common in pediatric and CHD patients. OBJECTIVE: The purpose of this study was to determine the incidence of MRI-related complications in pediatric and CHD patients with CIEDs, including epicardial and/or abandoned leads. METHODS: A multicenter retrospective review included patients with CIEDs who underwent any MRI between 2007 and 2022 at congenital cardiac centers. The primary outcome was any patient adverse event or clinically significant CIED change after MRI, defined as pacing lead capture threshold increase >0.5 V with output change, P- or R- wave amplitude decrease >50% with sensitivity change, or impedance change >50%. RESULTS: Across 14 institutions, 314 patients (median age 18.8 [1.3; 31.4] years) underwent 389 MRIs. There were 288 pacemakers (74%) and 87 implantable cardioverter-defibrillators (22%); 52% contained epicardial leads, and 14 (4%) were abandoned leads only. Symptoms or CIED changes occurred in 4.9% of MRI scans (6.1% of patients). On 9 occasions (2%), warmth or pain occurred. Pacing capture threshold or lead impedance changes occurred in 1.4% and 2.0% of CIEDs post-MRI and at follow-up. CONCLUSION: Our data provide evidence that MRIs can be performed in pediatric and CHD patients with CIEDs, including non-MRI-conditional CIEDs and epicardial and/or abandoned leads, with rare minor symptoms or CIED changes but no other complications.

PRDM16 Deletion Is Associated With Sex-dependent Cardiomyopathy and Cardiac Mortality: A Translational, Multi-Institutional Cohort Study.

BACKGROUND: 1p36 deletion syndrome can predispose to pediatric-onset cardiomyopathy. Deletion breakpoints are variable and may delete the transcription factor PRDM16. Early studies suggest that deletion of PRDM16 may underlie cardiomyopathy in patients with 1p36 deletion; however, the prognostic impact of PRDM16 loss is unknown. METHODS: This retrospective cohort included subjects with 1p36 deletion syndrome from 4 hospitals. Prevalence of cardiomyopathy and freedom from death, cardiac transplantation, or ventricular assist device were analyzed. A systematic review cohort was derived for further analysis. A cardiac-specific Prdm16 knockout mouse (Prdm16 conditional knockout) was generated. Echocardiography was performed at 4 and 6 to 7 months. Histology staining and qPCR were performed at 7 months to assess fibrosis. RESULTS: The retrospective cohort included 71 patients. Among individuals with PRDM16 deleted, 34.5% developed cardiomyopathy versus 7.7% of individuals with PRDM16 not deleted (P=0.1). In the combined retrospective and systematic review cohort (n=134), PRDM16 deletion-associated cardiomyopathy risk was recapitulated and significant (29.1% versus 10.8%, P=0.03). PRDM16 deletion was associated with increased risk of death, cardiac transplant, or ventricular assist device (P=0.04). Among those PRDM16 deleted, 34.5% of females developed cardiomyopathy versus 16.7% of their male counterparts (P=0.2). We find sex-specific differences in the incidence and the severity of contractile dysfunction and fibrosis in female Prdm16 conditional knockout mice. Further, female Prdm16 conditional knockout mice demonstrate significantly elevated risk of mortality (P=0.0003). CONCLUSIONS: PRDM16 deletion is associated with a significantly increased risk of cardiomyopathy and cardiac mortality. Prdm16 conditional knockout mice develop cardiomyopathy in a sex-biased way. Patients with PRDM16 deletion should be assessed for cardiac disease.

Comparison of Out-of-Hospital Cardiac Arrest Outcomes Between Asian and White Individuals in the United States.

Background Disparities in bystander cardiopulmonary resuscitation (CPR) and survival have been reported for Black and Hispanic individuals with out-of-hospital cardiac arrest (OHCA). Whether Asian individuals have lower rates of bystander CPR and survival for OHCA, as compared with White individuals, remains unknown. Methods and Results Within the US-based CARES (Cardiac Arrest Registry to Enhance Survival), we identified 278 989 OHCAs in Asian and White individuals during 2013 to 2021. Using hierarchical Poisson logistic regression with emergency medical service agency modeled as a random effect and patient and OHCA characteristics as fixed effects, we compared rates of bystander CPR, survival to discharge, and favorable neurological survival between Asian and White individuals with OHCA. Overall, 14 835 (5.3%) OHCAs occurred in Asian individuals. Compared with White individuals with OHCA, Asian individuals were older (67.0±17.6 versus 62.8±16.9 years) and were less likely to have drug overdose as the cause of OHCA (1.3% versus 6.6%) and a shockable arrest rhythm (19.2% versus 22.4%). Layperson bystander CPR rates were similar between Asian and White individuals (42.6% versus 42.1%; adjusted relative risk for Asian individuals, 0.99 [95% CI, 0.97-1.02]; P=0.69). However, rates of survival to discharge were lower in Asian individuals with OHCA (8.2% versus 10.3%; adjusted relative risk 0.92 [0.86-0.98] P=0.006). Similarly, the rate of favorable neurological survival was lower for Asian individuals (6.5% versus 8.7%; adjusted relative risk, 0.85 [0.79-0.91]; P<0.001). Conclusions Despite similar rates of bystander CPR, Asian individuals with OHCA have lower survival rates than White individuals with OHCA. The reasons for the lower survival rate deserve further study to determine whether there are disparities in resuscitation care between Asian and White individuals with OHCA.

Atrioventricular Nodal Ablation Is Not an Effective Treatment Strategy in Catecholaminergic Polymorphic Ventricular Tachycardia.

Catecholaminergic polymorphic ventricular tachycardia is a rare but lethal heritable arrhythmia syndrome associated with both atrial and ventricular arrhythmias. Treatment includes antiarrhythmics, sympathetic denervation, and implantable cardioverter-defibrillators. The use of atrioventricular nodal ablation as a treatment strategy to prevent ventricular arrhythmias in catecholaminergic polymorphic ventricular tachycardia was not found in the literature. This report describes a teenager with a presenting rhythm of atrial and ventricular fibrillation and cardiac arrest. Her clinical arrhythmia was predominantly atrial dysrhythmias, which delayed her diagnosis of catecholaminergic polymorphic ventricular tachycardia. Before her diagnosis, she underwent atrioventricular nodal ablation in an effort to prevent ventricular arrhythmias, which was ultimately ineffective. This report highlights the importance of recognizing atrial arrhythmias in catecholaminergic polymorphic ventricular tachycardia and provides evidence that atrioventricular nodal ablation is not an effective treatment strategy for this disease.

Asymptomatic Wolff-Parkinson-White Syndrome: An Ounce of Prevention Is Worth the Risk of Cure.

PURPOSE OF REVIEW: With increased electrocardiogram screening, asymptomatic preexcitation has become more prevalent. Historically, the asymptomatic-symptomatic dichotomy has directed management. This approach warrants scrutiny, as asymptomatic Wolff-Parkinson-White (WPW) syndrome is not without risk. Children may be unreliable symptom reporters, have atypical arrhythmia symptoms, yet have years to become symptomatic. RECENT FINDINGS: In a large WPW study, symptomatic patients were more likely to undergo ablation than asymptomatic patients, yet, except for symptoms, there were no differences in clinical or electrophysiology study (EPS) characteristics. Present data confirm real risk in asymptomatic WPW-sudden death can be the first symptom. Although malignant arrhythmias correlate better with EPS risk stratification than with symptoms, EPS data are imperfect predictors. Unlike adults with WPW, children have yet to prove survivorship. Asymptomatic children must be treated differently than adults. Sudden death risk is low but front-loaded in the young. An aggressive approach to asymptomatic WPW is warranted in this era of highly successful, low-risk catheter ablations.

Impact and Modifiers of Ventricular Pacing in Patients With Single Ventricle Circulation.

BACKGROUND: Palliation of the single ventricle (SV) circulation is associated with a burden of lifelong complications. Previous studies have identified that the need for a permanent ventricular pacing system (PPMv) may be associated with additional adverse long-term outcomes. OBJECTIVES: The goal of this study was to quantify the attributable risk of PPMv in patients with SV, and to identify modifiable risk factors. METHODS: This international study was sponsored by the Pediatric and Congenital Electrophysiology Society. Centers contributed baseline and longitudinal data for functionally SV patients with PPMv. Enrollment was at implantation. Controls were matched 1:1 to PPMv subjects by ventricular morphology and sex, identified within center, and enrolled at matched age. Primary outcome was transplantation or death. RESULTS: In total, 236 PPMv subjects and 213 matched controls were identified (22 centers, 9 countries). Median age at enrollment was 5.3 years (quartiles: 1.5-13.2 years), follow-up 6.9 years (3.4-11.6 years). Median percent ventricular pacing (Vp) was 90.8% (25th-75th percentile: 4.3%-100%) in the PPMv cohort. Across 213 matched pairs, multivariable HR for death/transplant associated with PPMv was 3.8 (95% CI 1.9-7.6; P < 0.001). Within the PPMv population, higher Vp (HR: 1.009 per %; P = 0.009), higher QRS z-score (HR: 1.19; P = 0.009) and nonapical lead position (HR: 2.17; P = 0.042) were all associated with death/transplantation. CONCLUSIONS: PPMv in patients with SV is associated with increased risk of heart transplantation and death, despite controlling for increased associated morbidity of the PPMv cohort. Increased Vp, higher QRS z-score, and nonapical ventricular lead position are all associated with higher risk of adverse outcome and may be modifiable risk factors.

The high-density grid catheter: A safe adjunctive tool in pediatric and complex congenital heart disease patients.

INTRODUCTION: The safety and utility of the Advisor™ High-Density Grid mapping catheter (HDGC) in children and congenital heart disease (CHD) patients are not well described. METHODS: A single-center retrospective cohort study of pediatric and CHD patients undergoing electrophysiology study and ablation to determine the effect of HDGC use on outcomes including complications, fluoroscopy use, procedure duration, acute ablation success, and arrhythmia recurrence. RESULTS: HDGC was used in 74/261 (28.3%) cases. HDGC subjects differed by median age (17 vs. 13 years; p < 0.001), weight (68 vs. 50 kg; p < 0.001), and prevalence of significant CHD (42% vs. 3%; p < 0.001). Arrhythmia substrates were dissimilar: HGDC cases had higher frequencies of intra-atrial re-entrant tachycardia (25.7% vs. 0.5%), atrial flutter (8.1% vs. 1.1%), ectopic atrial tachycardia (13.5% vs. 3.7%), and premature ventricular contractions (9.5% vs. 0.5%), and lower incidences of atrioventricular re-entrant tachycardia (16.2% vs. 46.1%). Complications were rare (n = 5, 1.9%) with no significant difference between groups (p = 1.00). Procedure duration-but not fluoroscopy exposure-was significantly longer in HDGC cases (median 256 vs. 216 min, p < 0.001). Acute success was lower (93.2% vs. 99.4%; p = 0.01) and recurrences higher (13.2% vs. 3.8%; p = 0.016) in HDGC compared to non-HDGC cases. CONCLUSION: HDGC use in children and CHD patients is safe and not associated with higher complication rates. The lower acute success and higher recurrence rates in HDGC cases likely reflect a bias toward HDGC use in more complex arrhythmia substrates rather than less favorable ablation outcomes.

IV Sotalol Use in Pediatric and Congenital Heart Patients: A Multicenter Registry Study.

Background There is limited information regarding the clinical use and effectiveness of IV sotalol in pediatric patients and patients with congenital heart disease, including those with severe myocardial dysfunction. A multicenter registry study was designed to evaluate the safety, efficacy, and dosing of IV sotalol. Methods and Results A total of 85 patients (age 1 day-36 years) received IV sotalol, of whom 45 (53%) had additional congenital cardiac diagnoses and 4 (5%) were greater than 18 years of age. In 79 patients (93%), IV sotalol was used to treat supraventricular tachycardia and 4 (5%) received it to treat ventricular arrhythmias. Severely decreased cardiac function by echocardiography was seen before IV sotalol in 7 (9%). The average dose was 1 mg/kg (range 0.5-1.8 mg/kg/dose) over a median of 60 minutes (range 30-300 minutes). Successful arrhythmia termination occurred in 31 patients (49%, 95% CI [37%-62%]) with improvement in rhythm control defined as rate reduction permitting overdrive pacing in an additional 18 patients (30%, 95% CI [19%-41%]). Eleven patients (16%) had significant QTc prolongation to >465 milliseconds after the infusion, with 3 (4%) to >500 milliseconds. There were 2 patients (2%) for whom the infusion was terminated early. Conclusions IV sotalol was safe and effective for termination or improvement of tachyarrhythmias in 79% of pediatric patients and patients with congenital heart disease, including those with severely depressed cardiac function. The most common dose, for both acute and maintenance dosing, was 1 mg/kg over ~60 minutes with rare serious complications.

mRNA Coronavirus Disease 2019 Vaccine-Associated Myopericarditis in Adolescents: A Survey Study.

In this survey study of institutions across the US, marked variability in evaluation, treatment, and follow-up of adolescents 12 through 18 years of age with mRNA coronavirus disease 2019 (COVID-19) vaccine-associated myopericarditis was noted. Only one adolescent with life-threatening complications was reported, with no deaths at any of the participating institutions.

Detection of Tachyarrhythmias in a Large Cohort of Infants Using Direct-to-Consumer Heart Rate Monitoring.

OBJECTIVE: Current estimates of the incidence of tachyarrhythmias in infants rely on clinical documentation and may not reflect the true rate in the general population. Our aim was to describe the epidemiology of tachyarrhythmia detected in a large cohort of infants using direct-to-consumer heart rate (HR) monitoring. STUDY DESIGN: Data were collected from Owlet Smart Sock devices used in infants in the US with birthdates between February 2017 and February 2019. We queried the HR data for episodes of tachyarrhythmia (HR of ≥240 bpm for >60 seconds). RESULTS: The study included 100 949 infants (50.8% male) monitored for more than 200 million total hours. We identified 5070 episodes of tachyarrhythmia in 2508 infants. The cumulative incidence of tachyarrhythmia in our cohort was 2.5% over the first year of life. The median age at the time of the first episode of tachyarrhythmia was 36 days (range, 1-358 days). Tachyarrhythmia was more common in infants with congenital heart disease (4.0% vs 2.4%; P = .015) and in females (2.7% vs 2.0%; P < .001). The median length of an episode was 7.3 minutes (range, 60 seconds to 5.4 hours) and the probability of an episode lasting longer than 45 minutes was 16.8% (95% CI, 15.4%-18.3%). CONCLUSIONS: We found the cumulative incidence of tachyarrhythmia among infants using direct-to-consumer HR monitors to be higher than previously reported in studies relying on clinical diagnosis. This finding may represent previously undetected subclinical disease in young infants, the significance of which remains uncertain. Clinicians should be prepared to discuss these events with parents.

An International Multicenter Evaluation of Type 5 Long QT Syndrome: A Low Penetrant Primary Arrhythmic Condition.

BACKGROUND: Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rare KCNE1 variants implicated in LQT5 was sought through an international multicenter collaboration. METHODS: Patients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries. KCNE1 variants were evaluated for ECG penetrance (defined as QTc >460 ms on presenting ECG) and genotype-phenotype segregation. Multivariable Cox regression was used to compare the associations between clinical and genetic variables with a composite primary outcome of definite arrhythmic events, including appropriate implantable cardioverter-defibrillator shocks, aborted cardiac arrest, and sudden cardiac death. RESULTS: A total of 32 distinct KCNE1 rare variants were identified in 89 probands and 140 genotype positive family members with presumed LQT5 and an additional 19 Type 2 Jervell and Lange-Nielsen syndrome patients. Among presumed LQT5 patients, the mean QTc on presenting ECG was significantly longer in probands (476.9±38.6 ms) compared with genotype positive family members (441.8±30.9 ms, P<0.001). ECG penetrance for heterozygous genotype positive family members was 20.7% (29/140). A definite arrhythmic event was experienced in 16.9% (15/89) of heterozygous probands in comparison with 1.4% (2/140) of family members (adjusted hazard ratio [HR] 11.6 [95% CI, 2.6-52.2]; P=0.001). Event incidence did not differ significantly for Type 2 Jervell and Lange-Nielsen syndrome patients relative to the overall heterozygous cohort (10.5% [2/19]; HR 1.7 [95% CI, 0.3-10.8], P=0.590). The cumulative prevalence of the 32 KCNE1 variants in the Genome Aggregation Database, which is a human database of exome and genome sequencing data from now over 140 000 individuals, was 238-fold greater than the anticipated prevalence of all LQT5 combined (0.238% vs 0.001%). CONCLUSIONS: The present study suggests that putative/confirmed loss-of-function KCNE1 variants predispose to QT prolongation, however, the low ECG penetrance observed suggests they do not manifest clinically in the majority of individuals, aligning with the mild phenotype observed for Type 2 Jervell and Lange-Nielsen syndrome patients.

Early experience with intravenous sotalol in children with and without congenital heart disease.

BACKGROUND: Arrhythmias are common in the pediatric population. In patients unable to take oral medications or in need of acute therapy, options of intravenous (IV) antiarrhythmic medications are limited. Recently IV sotalol has become readily available, but experience in children is limited. OBJECTIVE: The purpose of this study was to describe our initial experience with the use of IV sotalol in the pediatric population. METHODS: A retrospective study of all pediatric patients receiving IV sotalol was performed. Patient demographic characteristics, presence of congenital heart disease, arrhythmia type, efficacy of IV sotalol use, and adverse effects were evaluated. RESULTS: A total of 47 patients (26 (55%) male and 24 (51%) with congenital heart disease) received IV sotalol at a median age of 2.05 years (interquartile range 0.07-10.03 years) and a median weight of 12.8 kg (interquartile range 3.8-34.2 kg), and 13 (28%) received IV sotalol in the acute postoperative setting. Supraventricular arrhythmias occurred in 40 patients (85%) and ventricular tachycardia in 7 (15%). Among 24 patients receiving IV sotalol for an active arrhythmia, acute termination was achieved in 21 (88%). Twenty-three patients received IV sotalol as maintenance therapy for recurrent arrhythmias owing to inability to take oral antiarrhythmic medications; 19 (83%) were controlled with sotalol monotherapy. No patient required discontinuation of IV sotalol secondary to adverse effects, proarrhythmia, or QT prolongation. CONCLUSION: IV sotalol is an effective antiarrhythmic option for pediatric patients and may be an excellent agent for acute termination of active arrhythmias. It was well tolerated, with no patient requiring discontinuation secondary to adverse effects.

Utility and Safety of Combined Interventional Catheterization and Electrophysiology Procedures in a Children's Hospital.

BACKGROUND: Interventional cardiac catheterization (cath) and electrophysiology (EP) procedures are not routinely performed together. There are several perceived barriers affecting this practice, though there are also advantages for both the patient and practitioner to a combined approach. METHODS: This was a single-center retrospective study reviewing combined cath and EP procedures with a preprocedural intention to intervene at Texas Children's Hospital from 2001 to 2014. We excluded procedures in which the intended procedure was purely diagnostic in nature. RESULTS: A total of 121 patients requiring 125 procedures were identified, of which 61 patients underwent 62 procedures that met our inclusion criteria. Potential subgroups of interest included adult congenital heart disease patients (26% of cohort), single ventricle anatomy (34%), and heterotaxy (19%) and collectively 58% of procedures involved a patient in one of these groups. The combined nature of the procedure did not preclude a cath or EP intervention in any patient. There were no mortalities. There were three adverse events, affecting 4.8% of procedures. CONCLUSIONS: Combined interventional cardiac cath and EP procedures in pediatric patients and those with congenital heart disease can be performed safely in a high-volume center. These combined procedures save patients the risk and inconvenience of multiple procedures, and further investigation into cost savings is warranted.

Circadian Variation of Ventricular Arrhythmias in Catecholaminergic Polymorphic Ventricular Tachycardia.

OBJECTIVES: The aim of this paper was to investigate whether ventricular arrhythmias in children with catecholaminergic polymorphic ventricular tachycardia (CPVT) show circadian patterns. BACKGROUND: Circadian arrhythmic patterns have been established in long QT, Brugada, and early repolarization, but have not been investigated in CPVT. METHODS: This is a multicenter, retrospective review of pediatric CPVT patients, age <21 years at diagnosis. Timing of ventricular tachycardia (VT ≥3 beats) was assessed during 24-h continuous monitoring (Holter, implantable loop recorder, implantable cardioverter defibrillator) and by eliminating sleep hours, in addition to sporadic exercise stress tests. Morning was defined as 6:00 am to 11:59 am, afternoon 12:00 pm to 5:59 pm, and evening 6:00 pm to 11:59 pm. Distribution of VT events was compared by time of day, day of week, age, and sex. RESULTS: Eighty patients (53% male), 61% with an ICD, experienced 423 VT events during a median follow-up time of 6 years (interquartile range: 2 to 10 years). When compared to morning hours, VT was more likely to occur in the afternoon (odds ratio [OR]: 2.54; 95% confidence interval [CI]: 1.69 to 3.83) or evening hours (OR: 2.91; 95% CI: 1.82 to 4.67). The predominance of afternoon/evening events persisted regardless of age, gender, or day of the week. Among 50 patients who underwent exercise stress tests, VT was significantly more likely to occur in the afternoon (OR: 3.00; 95% CI: 1.39 to 6.48). CONCLUSIONS: In pediatric CPVT patients, ventricular arrhythmias are more likely to occur in the afternoon and evening hours. Because children's activity levels peak in both the morning and afternoon, the lack of arrhythmias in the morning hours raises questions whether factors other than adrenergic stimulation influence arrhythmia induction in pediatric patients with CPVT.

Rectus-Sparing Technique for Driveline Insertion of Ventricular Assist Device.

We present a new technique for driveline insertion of the HeartWare ventricular assist device (HVAD) designed to preserve the integrity of the abdominal wall structure. Because of the size of the HVAD driveline connector (12 mm in diameter: triple the size of the driveline cable), the standard tunneling maneuver can result in tearing of the abdominal wall muscle layer, which is a primary mechanism to prevent ascending driveline infection. We find that our technique is particularly useful in children because their abdominal wall muscles are more fragile and thereby prone to accidental injury with blunt penetration when the standard technique is used.

Posttranscriptional regulation of IL-13 in T cells: role of the RNA-binding protein HuR.

BACKGROUND: IL-13, a critical cytokine in allergy, is regulated by as-yet-elusive mechanisms. OBJECTIVE: We investigated IL-13 posttranscriptional regulation by HuR, a protein associating with adenylate-uridylate-rich elements in the 3' untranslated regions (UTRs) of mRNA, promoting mRNA stability and translation. METHODS: IL-13 mRNA decay was monitored in human T(H)2-skewed cells by using the transcriptional inhibitor actinomycin D. The IL-13 3'UTR was subcloned into an inducible beta-globin reporter transiently expressed in H2 cells in the absence or presence of overexpressed HuR. Association of HuR with IL-13 mRNA was detected by means of immunoprecipitation of ribonucleoprotein complexes and a biotin pull-down assay. The effects of HuR transient overexpression and silencing on IL-13 expression were investigated. RESULTS: IL-13 mRNA half-life increased significantly in restimulated T(H)2-skewed cells compared with baseline values. Decay of beta-globin mRNA was significantly faster in H2 cells transfected with the IL-13 3'UTR-containing plasmid than in those carrying a control vector. HuR overexpression increased the beta-globin IL-13 3'UTR reporter half-life. Significant enrichment of IL-13 mRNA was produced by means of immunoprecipitation of Jurkat cell ribonucleoprotein complexes with anti-HuR. HuR binding to the IL-13 3'UTR was confirmed by means of pull-down assay of biotin-labeled RNA probes spanning the IL-13 3'UTR. Two-dimensional Western blot analysis showed stimulus-induced posttranslational modification of HuR. In Jurkat cells mitogen-induced IL-13 mRNA was significantly affected by HuR overexpression and silencing. CONCLUSIONS: Mitogen-induced IL-13 expression involves changes in transcript turnover and a change in phosphorylation of HuR and its association with the mRNA 3'UTR.