Epicardial Pacing Outcomes in Infants with Heart Block: Lead and Device Complications from a Multicenter Experience.

BACKGROUND: Infants with complete heart block (CHB) require epicardial pacemaker (PM) insertion. Prior studies described epicardial pacing outcomes in infants and children though were limited by small and/or heterogeneous populations. OBJECTIVE: To explore patient and procedural-level associations with device complications in infants with CHB who received a permanent PM. METHODS: Multicenter, retrospective cohort study including infants receiving an epicardial PM between 2000-2021 for CHB. The primary outcome was time to device-related adverse event (DRAE): (1) lead failure requiring revision; (2) pocket infection; (3) exit block requiring increased pacing output; or (4) lead-related coronary artery compression. Time to event analysis was performed using the Kaplan-Meier method with a multivariable Cox proportional hazards model. RESULTS: 174 infants received an epicardial PM (282 bipolar, 39 unipolar leads) for CHB. Median age and weight at PM were 93.5 days and 4.5 kg, respectively. Pacing indication was postoperative CHB in 63% and congenital CHB in 37%. The median follow-up was 2.1 years. The primary outcome occurred in 26 infants at a median time to event of 0.6 years. Age ≤90 days at PM was the most significant risk factor for DRAE (HR 7.02, p<0.001), primarily driven by pocket infections. Lead failure occurred in 3% of leads with a 5- and 10-year freedom from failure of 93% and 83%, respectively. CONCLUSIONS: Device complications affect 15% of infants receiving a permanent PM for heart block. Age ≤90 days at PM implant is especially associated with infectious complications. Epicardial lead durability appears similar to previously reported pediatric experiences.

Preparticipation Cardiac Evaluation from the Pediatric Perspective.

Each year millions of children and adolescents undergo sports preparticipation evaluations (PPEs) before participating in organized sports. A primary aim of the PPE is to screen for risk factors associated with sudden cardiac death. This article is designed to summarize the current thoughts on the PPE with a specific slant toward the pediatric and early adolescent evaluation and how these evaluations may differ from those in adults.

Persistent Elevation of Troponin I in a Pediatric Patient Resulting From Macrotroponin Complex.

ABSTRACT: Although chest pain is a common chief complaint among pediatric patients, cardiac pathology historically has accounted for a small percentage of cases. However, the emergence of COVID-19 and particularly its potential for leading to multisystem inflammatory syndrome has changed the threshold for the evaluation of cardiac etiologies of chest pain. This evaluation often includes measurement of the serum cardiac troponin I level. We present a case of a 16-year-old male athlete who presented to an outside emergency department with chest pain and was found to have elevated serum troponin I levels. Despite sports restriction, his troponin level remained elevated for months in the absence of other clinical findings and he was subsequently referred to our outpatient pediatric cardiology clinic. Further laboratory evaluation revealed that, in addition to troponin I, the assay measured an immune complex of uncertain significance formed by anti-troponin I antibodies bound to troponin I, known as macrotroponin. Delayed clearance of this complex from the bloodstream can result in overestimation of troponin I levels that can affect clinical management and create anxiety for our patients and their families. Macrotroponin complex deserves increased recognition among the research and clinical communities, especially in the pediatric realm.

Preparticipation Cardiac Evaluation from the Pediatric Perspective.

Each year millions of children and adolescents undergo sports preparticipation evaluations (PPEs) before participating in organized sports. A primary aim of the PPE is to screen for risk factors associated with sudden cardiac death. This article is designed to summarize the current thoughts on the PPE with a specific slant toward the pediatric and early adolescent evaluation and how these evaluations may differ from those in adults.

QRS fragmentation and prolongation as predictors of exercise capacity in patients after Fontan palliation.

INTRODUCTION: Patients with Fontan anatomy are at increased risk for exercise intolerance and early morbidity and mortality. QRS complex fragmentation (fQRS) and prolongation have been studied in multiple heart diseases, but their clinical importance is unknown in the Fontan population. METHODS: A retrospective cross-sectional study was performed. ECGs were evaluated for QRS prolongation (>98 percentile for age) and fQRS (≥3 R-waves/notches in the R/S complex [more than two in RBBB] in ≥2 contiguous leads). The primary outcome measures were CPET performance. RESULTS: Total 90 patients (median age 18 years, 57% male, 59% RV dominant) were included; 13% had fQRS and 31% had prolonged QRS. Demographically, patients with fQRS or prolonged QRS were like those without. Peak VO2 (64% vs. 63%, p .45), VE/VCO2 slope (85% vs. 88%, p = .74), and O2 pulse (149% vs. 129%, p = .83) were similar in the fQRS group versus those without. Upon multi-variable regression, body mass index (ß = -0.38, p < .01) and QRS duration (ß = -0.29, p < .01) were independently associated with % predicted VO2; fQRS was not. Lower cardiac index (2.2 vs. 2.8 L/min/m2 , p = .03) and higher ventricular end-diastolic pressure (13 vs. 10 mmHg, p = .02) was seen with fQRS. CONCLUSIONS: QRS fragmentation is present in patients with Fontan physiology. fQRS showed no association with CPET performance but was related to invasive hemodynamic markers of ventricular performance. QRS duration may be a better predictor of exercise function following Fontan.

Exploring factors associated with health disparities in asthma and poorly controlled asthma among school-aged children in the U.S.

Objective: Certain populations suffer disproportionately from asthma and asthma morbidity. The objective was to provide a national descriptive profile of asthma control and treatment patterns among school-aged children (SAC: aged 6-17) in the U.S. Methods: This was a cross-sectional analysis using the nationally representative 2007-2014 Medical Expenditure Panel Survey. Among SAC with asthma, indicators of poor control included: exacerbation/asthma attack; >3 canisters short-acting beta agonist (SABA)/3 months; and asthma-specific Emergency Department or inpatient visits (ED/IP). Results: Non-Hispanic black, non-Hispanic multiple races, Puerto Rican, obese, Medicaid, poor, ≥2 non-asthma chronic comorbidities (CC), and family average CC ≥ 2 were associated with higher odds of having asthma. The following had significantly higher odds ratios (OR) of excessive SABA use compared to non-Hispanic whites [OR; CI; p < 0.05]: Puerto Rican (3.8; 2.1-6.9), Mexican (3.6; 2.0-6.4), Central/South American (3.0; 1.2-7.7), Hispanic-other (3.1; 1.1-9.0), non-Hispanic black (2.5; 1.6-3.9), and non-Hispanic Asian (4.0; 1.7-9.2). SABA OR were also significant for Spanish spoken at home (2.5; 1.6-3.8), obese (2.1; 1.3-3.3), Medicaid (2.9; 2.0-4.1), no medical insurance (2.1; 1.1-4.1), no prescription insurance (2.5; 1.8-3.5), poor (2.8; 1.7-4.7), CC ≥ 2 (2.1; 1.6-2.8), parent-without high-school degree (2.5; 1.8-3.6), parent-SF-12 Physical Component Scale <50 (1.6; 1.2-2.1) and Mental Component Scale <50 (1.5; 1.1-2.0). Significant differences also existed across subgroups for ED/IP visits. Conclusions: There are disparities in asthma control and prevalence among certain populations in the U.S. These results provide national data on disparities in several indicators of poor asthma control beyond the standard race/ethnicity groupings.

The national burden of poorly controlled asthma, school absence and parental work loss among school-aged children in the United States.

OBJECTIVE: The degree of poorly controlled asthma and its association with missed school days and parental missed work days is not well understood. METHODS: This was a retrospective analysis of missed school days and missed work days for school-aged children (SAC; aged 6-17) and their caregivers in the nationally representative 2007-2013 Medical Expenditure Panel Survey (MEPS). Indicators of poor asthma control included: exacerbation in previous 12 months; use of >3 canisters of short-acting beta agonist (SABA) in 3 months; and annual asthma-specific (AS) Emergency Department (ED) or inpatient (IP) visits. Negative binomial regression was used for missed school days, and a Heckman two-step selection model was used for missed work days. All analyses controlled for sociodemographics and other covariates. RESULTS: There were 44,320 SAC in MEPS, of whom 5,890 had asthma. SAC with asthma and an indicator of poor control missed more school days than SAC without asthma: exacerbation (1.8 times more; p < 0.001); >3 canisters SABA (2.7 times more; p < 0.001) and ED/IP visit (3.8 times more; p < 0.001). The parents/caregivers of SAC with asthma and an exacerbation missed 1.2 times more work days (p < 0.05), while those with SAC with asthma and an ED/IP visit missed 1.8 times more work days (p < 0.01) than the parents of SAC without asthma. CONCLUSIONS: This study provides evidence of the significant national burden of poorly controlled asthma due to missed school and work days in the United States. More effective and creative asthma management strategies, with collaboration across clinical, community and school-based outreach, may help address this burden.

Effects of persistent Fontan fenestration patency on cardiopulmonary exercise testing variables.

Cardiopulmonary exercise testing (CPET) aids in clinical assessment of patients with Fontan circulation. Effects of persistent fenestration on CPET variables have not been clearly defined. Associations between fenestration and CPET variables at anaerobic threshold (AT) and peak exercise were explored in the Pediatric Heart Network Fontan Cross-Sectional Study cohort. Fenestration patency was associated with a greater decrease in oxygen saturation from rest to peak exercise (fenestration -4.9 ± 3.8 v. nonfenestration -3 ± 3.5; P < .001). Physiological dead space at peak exercise was higher in fenestrated v. nonfenestrated (25.2 ± 16.1 v. 21.4 ± 15.2; P = .03). There was a weak association between fenestration patency and maximal work and heart rate. Fenestration patency was also weakly correlated with oxygen pulse, work and VE/VCO2 at AT. The effect of persistent fenestration on CPET measurements was minimal in this study, likely due to the cross-sectional design.

Sex-specific lean body mass predictive equations are accurate in the obese paediatric population.

BACKGROUND: The clinical assessment of lean body mass (LBM) is challenging in obese children. A sex-specific predictive equation for LBM derived from anthropometric data was recently validated in children. AIM: The purpose of this study was to independently validate these predictive equations in the obese paediatric population. SUBJECTS AND METHODS: Obese subjects aged 4-21 were analysed retrospectively. Predicted LBM (LBMp) was calculated using equations previously developed in children. Measured LBM (LBMm) was derived from dual-energy x-ray absorptiometry. Agreement was expressed as [(LBMm-LBMp)/LBMm] with 95% limits of agreement. RESULTS: Of 310 enrolled patients, 195 (63%) were females. The mean age was 11.8 ± 3.4 years and mean BMI Z-score was 2.3 ± 0.4. The average difference between LBMm and LBMp was -0.6% (-17.0%, 15.8%). Pearson's correlation revealed a strong linear relationship between LBMm and LBMp (r = 0.97, p < 0.01). CONCLUSION: This study validates the use of these clinically-derived sex-specific LBM predictive equations in the obese paediatric population. Future studies should use these equations to improve the ability to accurately classify LBM in obese children.

Safety and tolerability of omalizumab.

BACKGROUND: Omalizumab (Xolair) is a recombinant humanized monoclonal anti-IgE antibody with proven efficacy in patients with moderate-to-severe and severe persistent allergic (IgE-mediated) asthma. OBJECTIVE: To review clinical study data to assess the safety profile of omalizumab. METHODS: We analysed the safety of omalizumab using data from completed clinical studies (up to 1 year) involving more than 7500 patients with asthma, rhinitis or related conditions and up to 4 years in one study of patients with severe allergic asthma, as well as post-marketing safety data. Analysis focuses on the risk of immune-system effects, hypersensitivity reactions, malignant neoplasia, parasitic infections and thrombocytopenia. RESULTS: Omalizumab exhibited a good safety and tolerability profile that was maintained up to 4 years in one study. The incidence of anaphylaxis was 0.14% in omalizumab-treated patients and 0.07% in control patients. No omalizumab-treated patient developed measurable anti-omalizumab antibodies. Post-marketing, based on estimated exposure of 57,300 patients (June 2003-December 2006), the frequency of anaphylaxis attributed to omalizumab use was estimated to be at least 0.2% of patients. Current clinical trial data do not support an increased risk of malignant neoplasia or thrombocytopenia with omalizumab. CONCLUSION: Data indicate that the proven efficacy of add-on omalizumab in patients with moderate-to-severe or severe allergic asthma is accompanied by a favourable safety and tolerability profile.

Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma.

BACKGROUND: A recombinant humanized anti-IgE mAb, omalizumab, forms complexes with free IgE, blocking its interaction with mast cells and basophils; as a consequence, it might be effective in the treatment of asthma. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of omalizumab in the treatment of inhaled corticosteroid-dependent asthma. METHODS: In this phase III, double-blinded, placebo-controlled trial, 525 subjects with severe allergic asthma requiring daily inhaled corticosteroids were randomized to receive placebo or omalizumab subcutaneously every 2 or 4 weeks, depending on baseline IgE level and body weight. Inhaled corticosteroid doses were kept stable over the initial 16 weeks of treatment and tapered during a further 12-week treatment period. RESULTS: Omalizumab treatment resulted in significantly fewer asthma exacerbations per subject and in lower percentages of subjects experiencing an exacerbation than placebo treatment during the stable steroid phase (0.28 vs 0.54 [P =.006] and 14.6% vs 23.3% [P =.009], respectively) and during the steroid reduction phase (0.39 vs 0.66 [P =.003] and 21.3% vs 32.3% [P =.004], respectively). Beclomethasone dipropionate reduction was significantly greater with omalizumab treatment than with placebo (median 75% vs 50% [P <.001]), and beclomethasone dipropionate discontinuation was more likely with omalizumab (39.6% vs 19.1% [P <.001]). Improvements in asthma symptoms and pulmonary function occurred along with a reduction in rescue beta-agonist use. Omalizumab was well tolerated, with an adverse-events profile similar to that of placebo. CONCLUSION: The addition of omalizumab to standard asthma therapy reduces asthma exacerbations and decreases inhaled corticosteroid and rescue medication use.

Predictors of psychological adjustment in school-age children infected with HIV.

OBJECTIVE: To assess for significant differences in psychological functioning between HIV-infected children and a demographically matched healthy control group and to examine the utility of applying a stress and coping model to children with HIV disease. METHODS: Participants included HIV-infected children (ages 6-16) and their caregivers (n = 36) and a control group of healthy children and their caregivers (n = 32). During routine clinic visits, children completed measures of psychological adjustment, health locus of control, and coping style, and caregivers completed measures of their own and their child's psychological adjustment. RESULTS: Caregiver-reported and child self-reported psychological adjustment scores did not significantly differ between the HIV and control groups, with the exception of significantly more internalizing behavior problems reported in the control group. Hierarchical multiple regression analyses revealed that the stress and coping model accounted for 36% of the variance in HIV-infected children's self-reported psychological adjustment. In addition, child age and coping style were significant predictors of child self-reported psychological adjustment, but not of caregiver-reported child adjustment. CONCLUSIONS: Approximately 25% of children with HIV disease exhibited clinically significant emotional or behavioral problems; however, even higher rates of psychological adjustment problems were found in healthy children. Children with HIV disease who have not been told their diagnosis and children who endorse more emotion-focused coping strategies tend to exhibit more psychological adjustment problems.

New treatments and the future role of immunotherapy: anti-IgE.

OBJECTIVE: The review outlines an overview of anti-IgE, along with a description of the production and mechanism of action of the finished molecule. The immunologic effect of the drug and the drug complexes are detailed, and proof of efficacy is offered. The review also speculates about the role of anti-IgE in clinical use, along with potential future therapies, including gene substitution and genetic alteration. DATA SOURCES: The author reviewed literature studying IgE and anti-IgE antibody. STUDY SELECTION: The expert opinion of the author was used to select relevant data. RESULTS: The injection of anti-IgE results in four proven reactions: free antibody is bound; not bound antibody is not dislodged to any degree; plasma B cell production of IgE drops; and high-affinity Fc epsilon RI and low-affinity Fc epsilon RII on mast cells and basophils are downregulated. CONCLUSIONS: Based on observation of clinical reaction, anti-IgE is truly immunotherapy. Current opinion among clinical investigators about the impact of the impending approval of this new drug is that it will not replace standard immunotherapy. How it will fit into the armamentarium of physicians dealing with allergic disease, and protocols for its use, are still being debated.

Olopatadine ophthalmic solution adjunctive to loratadine compared with loratadine alone in patients with active seasonal allergic conjunctivitis symptoms.

BACKGROUND: Olopatadine ophthalmic solution 0.1% (Patanol, Alcon Laboratories, Fort Woth, TX) is approved for the treatment of the signs and symptoms of allergic conjunctivitis. Loratadine 10 mg (Claritin, Schering-Plough, Madison, NJ) is a nonsedating oral antihistamine approved for the treatment of the signs and symptoms of allergic rhinitis. OBJECTIVE: To compare the efficacy of olopatadine used adjunctively with loratadine versus loratadine alone in patients with seasonal allergic conjunctivitis. METHODS: This three-center, observer-masked, treatment-controlled, randomized, parallel-group study involved patients aged 7 to 74 years with seasonal allergic conjunctivitis. Patients were treated for 7 days with either olopatadine twice daily adjunctive to loratadine once daily or only loratadine once daily. Efficacy variables (ocular itching and redness, physician's impression, patient's impression, patient diary ratings of ocular redness and itching), and safety parameters were evaluated during the screening visit and on days 0, 3, and 7. Patients completed the rhinoconjunctivitis quality of life questionnaire on days 0 and 7. RESULTS: Ninety-four patients received study drug. Patients receiving olopatadine twice daily in addition to loratadine once daily exhibited less ocular itching (P = 0.0436) and rated their ocular condition as more improved compared with those receiving loratadine alone (P < 0.0022). Twenty minutes after initial dosing, olopatadine plus loratadine relieved ocular itching and redness significantly better than loratadine alone (P = 0.001). Both treatment groups showed clinically meaningful improvements in overall quality of life in all but one of the rhinoconjunctivitis quality of life questionnaire domains. Overall, and in most domains, olopatadine plus loratadine also provided significantly better (P < 0.05) quality of life than loratadine alone at day 7. CONCLUSIONS: Compared with loratadine alone, olopatadine adjunctive to loratadine provides greater relief of ocular itching and redness, a better quality of life, and is well tolerated in patients with seasonal allergic conjunctivitis.

Salmeterol added to inhaled corticosteroid therapy is superior to doubling the dose of inhaled corticosteroids: a randomized clinical trial.

This randomized, double-blind, double-dummy, parallel group clinical trial compared the efficacy and safety of adding salmeterol xinafoate to concurrent inhaled beclomethasone dipropionate therapy with doubling the dose of beclomethasone dipropionate in patients experiencing symptoms on low-dose beclomethasone. Salmeterol added to low-dose beclomethasone was superior (p < or = 0.05) to doubling the dose of beclomethasone in improving peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV1), and in reducing symptoms of asthma, sleep loss, nighttime awakenings, and use of albuterol. Both treatment regimens had comparable safety profiles. In asthma patients inadequately controlled despite the use of low-dose inhaled corticosteroids (i.e., less than 400 microg per day), the addition of salmeterol may be a more effective treatment option than doubling the dose of inhaled corticosteroids.

The effects of triamcinolone acetonide aqueous nasal spray on adrenocortical function in children with allergic rhinitis.

BACKGROUND: Suppression of adrenocortical function, a risk associated with oral corticosteroids, is minimized with intranasal corticosteroids. Triamcinolone acetonide (TAA) aqueous nasal spray, at therapeutic doses, has no measurable effect on adrenocortical function in adults with allergic rhinitis. OBJECTIVE: This double-blind, placebo-controlled study compared the effect of once-daily TAA aqueous nasal spray (220 or 440 microg) with placebo on adrenocortical function after 6 weeks of treatment in pediatric (children 6 to 12 years of age) patients with allergic rhinitis. The pharmacokinetic profile of TAA was examined after once-daily intranasal administration of TAA aqueous nasal spray 440 microg for 6 weeks. METHODS: Eighty children received TAA aqueous nasal spray 220 microg or 440 microg or placebo for 6 weeks. Adrenocortical function was assessed by analyzing plasma cortisol levels before stimulation (0 hour) and at 30 and 60 minutes after a rapid 1-hour intravenous cosyntropin stimulation test performed before treatment and after 6 weeks of treatment. Samples for pharmacokinetic evaluation were collected from 19 patients at baseline (0 hour) and at 0.5, 1, 1.5, and 6 hours after the final dose of study medication. RESULTS: After 6 weeks, no significant effects on adrenocortical function were observed at 30 or 60 minutes after cosyntropin stimulation with either dose of TAA aqueous nasal spray. TAA concentrations in plasma showed rapid elimination of the drug, with little or no accumulation. CONCLUSIONS: TAA aqueous nasal spray (220 or 440 microg/day) has no measurable effect on adrenocortical function in pediatric patients with allergic rhinitis. Pharmacokinetic parameters after 440 microg/day of TAA aqueous nasal spray indicate a rapid decline of plasma drug levels, with little or no systemic accumulation of study drug.

[The effect of 4-aminopyridine on indirectly evoked contractions of the diaphragm in rats in situ]. / Uticaj 4-aminopiridina na indirektno izazvane kontrakcije dijafragme pacova in situ.

The aim of the present study was to investigate the influence of three doses of 4-aminopyridine (1, 3 and 10 mg/kg i.v.) on the amplitude of contraction of rat diaphragm indirectly stimulated by electrical impulses of various frequencies (0.1, 1, 10, 50 and 100 Hz). All the doses used significantly augmented the post-tetanic single twitch potentiation after stimulation with 100 Hz (by 35-40%). Doses of 3 and 10 mg/kg i.v. of 4-aminopyridine significantly increased the contractile response to the 10 Hz stimulation (by 73-77%), while only 3 mg/kg i.v. significantly (by 35-39%) increased the amplitude of initial single twitches. It is concluded that the 4-aminopyridine-induced blockade of presynaptic potassium channels caused potentiation of the indirectly evoked contractions of rat diaphragm in situ, which is both dose- and frequency-dependent.

Separation of alpha-adrenergic and imidazoline/guanidinium receptive sites (IGRS) activity in a series of imidazoline analogues of cirazoline.

To characterize the structure-activity relationship between alpha 1-adrenergic receptors and the family of imidazoline/guanidinium receptive sites (IGRS), we synthesized and characterized a series of analogues of cirazoline, an imidazoline with high affinity for alpha 1-adrenergic receptors and IGRS. Analysis of potency, affinity and efficacy of the synthesized molecules indicate different structure-activity relationships for IGRS and alpha-adrenergic receptors. Cirazoline exhibits a 25-fold higher affinity for IGRS (pKi 7.9) than for alpha 1-adrenergic receptors. Replacement of the cyclopropyl ring with an isopropoxy group resulted in a molecule that was 20-fold more selective for alpha 1-adrenergic receptors than for IGRS, i.e. a 500-fold increase in selectivity relative to cirazoline. The unsubstituted derivative 3 and the methyl and allyl substituted analogues 4 and 12 are of particular interest: compounds 3 and 4 recognize IGRS with high affinity (pKi 7.83 and 8.17) and high selectivity (398 and 123) with respect to the alpha 1-adrenergic receptor; compound 12 also recognizes IGRS with high affinity (pKi 8.08) and high selectivity (228 and 138) with respect to the alpha 2B and alpha 2C-adrenergic receptor subtypes. Thanks to their IGRS selectivity, these compounds represent novel and valuable pharmacological tools for the characterization and elucidation of the physiological role of these novel sites.