Effect of Parenchymal Arachnoid on Brain Fluid Transport.

Introduction: The pia-arachnoid is a critical component of cerebrospinal fluid removal. It covers and invaginates into the brain parenchyma, and physiologic failure results in hydrocephalus and cerebral edema. The purpose of this study was to characterize the role of arachnoid within brain parenchyma and determine if water flux and solute transport are affected by these intra-parenchymal cells. Methods: An immortalized arachnoid rat cell line was used to seed 300-µm organotypic rat brain slices of 4-week-old rats. Fluid and tracer transport analyses were conducted following a 7-10 day intraparenchymal growth period. The development of an arachnoid brain slice model was characterized using diffusion chamber experiments to calculate permeability, diffusion coefficient, and flux. Results: Labeled rat arachnoid cells readily penetrated organotypic cultures for up to 10 days. A significant reduction of dye and water flux across arachnoid-impregnated brain slices was observed after 3 hours in the diffusion chamber. Permeability decreased in whole brain slices containing arachnoid cells compared to slices without arachnoid cells. In comparison, a significant reduction of dextran across all slices occurred when molecular weights increased from 40 to 70 kDa. Conclusion: Tracer and small molecule studies show that arachnoid cells' presence significantly impacts water's movement through brain parenchyma. Size differential experiments indicate that the permeability of solute changed substantially between 40 and 70 kDa, an essential marker of blood-CSF barrier definition. We have developed an arachnoid organotypic model that reveals their ability to alter permeability and transport.

Effect of Ablation Energy Source on Outcomes of Slow Pathway Modification for AVNRT in Children.

BACKGROUND: Selection of radiofrequency ablation (RF) or cryoablation (Cryo) for atrioventricular nodal re-entrant tachycardia (AVNRT) in children remains controversial due to a lack of contemporary comparison studies in this population. OBJECTIVES: This study sought to compare outcomes of RF and Cryo for AVNRT in the pediatric population. METHODS: AVNRT ablation outcomes were retrospectively analyzed utilizing the National Cardiovascular Data Registry IMPACT (Improving Pediatric and Adult Congenital Treatment) Registry from April 2016 to March 2019. Data from subjects 1 to 21 years of age undergoing elective first-time slow pathway (SP) modification for AVNRT were included. Exclusion criteria included <1 year of age, congenital heart disease, and >1 ablation target. Cases were analyzed by ablation energy: 1) RF only; 2) Cryo only; 3) radiofrequency ablation switching to cryoablation (RF→Cryo); and 4) cryoablation switching to radiofrequency ablation (Cryo→RF). The primary outcome was acute ablation failure. Secondary outcomes included in-hospital adverse events. RESULTS: Among 2,448 patients (mean age 13.6 ± 3.4 years, 60% female), RF only was employed in 43% (n = 1,046), Cryo only in 49% (n = 1,201), RF→Cryo in 6% (n = 135), and Cryo→RF in 66 (3%). Acute ablation failure occurred in 1.3% (n = 33), with no difference by energy source (1% in RF only, 1.5% in Cryo only, 1.5% in RF→Cryo, 3% in Cryo→RF; P = 0.5). Atrioventricular (AV) block requiring permanent pacemaker did not occur in any group; transient AV block occurred in 0.4% of the cohort, with no difference by group. CONCLUSIONS: In this largest pediatric study of AVNRT ablation, RF and Cryo demonstrated comparable high acute success and rare documentation of AV block that did not result in temporary or permanent pacing. Longitudinal data are important for further comparison of these modalities with regard to recurrence risk and late complications.

Epidemiology of Postoperative Junctional Ectopic Tachycardia in Infants Undergoing Cardiac Surgery.

BACKGROUND: Junctional ectopic tachycardia (JET) complicates congenital heart surgery in 2% to 8.3% of cases. JET is associated with postoperative morbidity in single-center studies. We used the Pediatric Cardiac Critical Care Consortium data registry to provide a multicenter epidemiologic description of treated JET. METHODS: This is a retrospective study (February 2019-August 2022) of patients with treated JET. Inclusion criteria were (1) <12 months old at the index operation, and (2) treated for JET <72 hours after surgery. Diagnosis was defined by receiving treatment (pacing, cooling, and medications). A multilevel logistic regression analysis with hospital random effect identified JET risk factors. Impact of JET on outcomes was estimated by margins/attributable risk analysis using previous risk-adjustment models. RESULTS: Among 24,073 patients from 63 centers, 1436 (6.0%) were treated for JET with significant center variability (0% to 17.9%). Median time to onset was 3.4 hours, with 34% present on admission. Median duration was 2 days (interquartile range, 1-4 days). Tetralogy of Fallot, atrioventricular canal, and ventricular septal defect repair represented >50% of JET. Patient characteristics independently associated with JET included neonatal age, Asian race, cardiopulmonary bypass time, open sternum, and early postoperative inotropic agents. JET was associated with increased risk-adjusted durations of mechanical ventilation (incidence rate ratio, 1.6; 95% CI, 1.5-1.7) and intensive care unit length of stay (incidence rate ratio, 1.3; 95% CI, 1.2-1.3), but not mortality. CONCLUSIONS: JET is treated in 6% of patients with substantial center variability. JET contributes to increased use of postoperative resources. High center variability warrants further study to identify potential modifiable factors that could serve as targets for improvement efforts to ameliorate deleterious outcomes.

Limited Relationship Between Echocardiographic Measures and Electrocardiographic Markers of Left Ventricular Size in Healthy Children.

Pediatric ECG standards have been defined without echocardiographic confirmation of normal anatomy. The Pediatric Heart Network Normal Echocardiogram Z-score Project provides a racially diverse group of healthy children with normal echocardiograms. We hypothesized that ECG and echocardiographic measures of left ventricular (LV) dimensions are sufficiently correlated in healthy children to imply a clinically meaningful relationship. This was a secondary analysis of a previously described cohort including 2170 digital ECGs. The relationship between 6 ECG measures associated with LV size were analyzed with LV Mass (LVMass-z) and left ventricular end-diastolic volume (LVEDV-z) along with 11 additional parameters. Pearson or Spearman correlations were calculated for the 78 ECG-echocardiographic pairs with regression analyses assessing the variance in ECG measures explained by variation in LV dimensions and demographic variables. ECG/echocardiographic measurement correlations were significant and concordant in 41/78 (53%), though many were significant and discordant (13/78). Of the 6 ECG parameters, 5 correlated in the clinically predicted direction for LV Mass-z and LVEDV-z. Even when statistically significant, correlations were weak (0.05-0.24). R2 was higher for demographic variables than for echocardiographic measures or body surface area in all pairs, but remained weak (R2 ≤ 0.17). In a large cohort of healthy children, there was a positive association between echocardiographic measures of LV size and ECG measures of LVH. These correlations were weak and dependent on factors other than echocardiographic or patient derived variables. Thus, our data support deemphasizing the use of solitary, traditional measurement-based ECG markers traditionally thought to be characteristic of LVH as standalone indications for further cardiac evaluation of LVH in children and adolescents.

How we do it: Cardiac implantable devices are not a contraindication to MRI: time for a paradigm shift.

Magnetic resonance imaging (MRI) is now an indispensable diagnostic tool in medicine due to its outstanding contrast resolution and absence of radiation exposure, enabling detailed tissue characterization and three-dimensional anatomical representation. This is especially important when evaluating individuals with congenital heart disease (CHD) who frequently require cardiac implantable electrical devices (CIEDs). While MRI safety issues have previously limited its use in patients with CIEDs, new advances have called these limitations into question. However, difficulties persist in the pediatric population due to the continued lack of specific safety data both related to imaging young children and the specific CIED devices they often require. This paper discusses MRI safety considerations related to imaging patients with CIEDs, investigates pediatric-specific problems, and describes thorough methods for safe MRI access, highlighting the significance of specialized institutional guidelines.

"But for the blind spot": Accuracy and diagnostic performance of smart watch cardiac features in pediatric patients.

BACKGROUND: The Apple Watch™ (AW) offers heart rate (HR) tracking by photoplethysmography (PPG) and single-lead electrocardiographic (ECG) recordings. The accuracy of AW-HR and diagnostic performance of AW-ECGs among children during both sinus rhythm and arrhythmias have not been explored. OBJECTIVE: The purposes of this study were to assess the accuracy of AW-HR measurements compared to gold standard modalities in children during sinus rhythm and arrhythmias and to identify non-sinus rhythms using AW-ECGs. METHODS: Subjects ≤18 years wore an AW during (1) telemetry admission, (2) electrophysiological study (EPS), or (3) exercise stress test (EST). AW-HRs were compared to gold standard modality values. Recorded AW-ECGs were reviewed by 3 blinded pediatric electrophysiologists. RESULTS: Eighty subjects (median age 13 years; interquartile range 1.0-16.0 years; 50% female) wore AW (telemetry 41% [n = 33]; EPS 34% [n = 27]; EST 25% [n = 20]). A total of 1090 AW-HR measurements were compared to time-synchronized gold standard modality HR values. Intraclass correlation coefficient (ICC) was high 0.99 (0.98-0.99) for AW-HR during sinus rhythm compared to gold standard modalities. ICC was poor comparing AW-HR to gold standard modality HR in tachyarrhythmias (ICC 0.24-0.27) due to systematic undercounting of AW-HR values. A total of 126 AW-ECGs were reviewed. Identification of non-sinus rhythm by AW-ECG showed sensitivity of 89%-96% and specificity of 78%-87%. CONCLUSIONS: We found high levels of agreement for AW-HR values with gold standard modalities during sinus rhythm and poor agreement during tachyarrhythmias, likely due to hemodynamic effects of tachyarrhythmias on PPG-based measurements. AW-ECGs had good sensitivity and moderate specificity in identification of non-sinus rhythm in children.

Patterns of Electrocardiographic Abnormalities in Children with Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM), a common cardiomyopathy in children, is an important cause of morbidity and mortality. Early recognition and appropriate management are important. An electrocardiogram (ECG) is often used as a screening tool in children to detect heart disease. The ECG patterns in children with HCM are not well described.ECGs collected from an international cohort of children, and adolescents (≤ 21 years) with HCM were reviewed. 482 ECGs met inclusion criteria. Age ranged from 1 day to 21 years, median 13 years. Of the 482 ECGs, 57 (12%) were normal. The most common abnormalities noted were left ventricular hypertrophy (LVH) in 108/482 (22%) and biventricular hypertrophy (BVH) in 116/482 (24%) Of the patients with LVH/BVH (n = 224), 135 (60%) also had a strain pattern (LVH in 83, BVH in 52). Isolated strain pattern (in the absence of criteria for hypertrophy) was seen in 43/482 (9%). Isolated pathologic Q waves were seen in 71/482 (15%). Pediatric HCM, 88% have an abnormal ECG. The most common ECG abnormalities were LVH or BVH with or without strain. Strain pattern without hypertrophy and a pathologic Q wave were present in a significant proportion (24%) of patients. Thus, a significant number of children with HCM have ECG abnormalities that are not typical for "hypertrophy". The presence of the ECG abnormalities described above in a child should prompt further examination with an echocardiogram to rule out HCM.

Risk Stratification in Pediatric Wolff-Parkinson-White: Practice Variation Among Pediatric Cardiologists and Electrophysiologists.

BACKGROUND: Published guidelines provide recommendations for risk stratification in pediatric Wolff-Parkinson-White (WPW). There are no data on provider concordance with these guidelines. We hypothesized that significant practice variation exists between pediatric cardiologists (PC) and electrophysiologists (EP). METHOD: The records of all patients, age 8 to 21 years, with a new ECG diagnosis of WPW between 1/1/2013 and 12/31/2018, from a single center, were retrospectively reviewed. Subjects were categorized on the basis of symptoms and resting ECG findings as one of the following: asymptomatic intermittent WPW, asymptomatic persistent WPW, or symptomatic WPW. The performance and results of diagnostic testing, including Holter monitor, event monitor, exercise stress test (EST), and electrophysiology study (EPS), were recorded. The primary outcome was concordance with published guidelines. A secondary outcome was documentation of a discussion of sudden cardiac death (SCD) risk. RESULTS: 615 patient encounters were analyzed in 231 patients with newly diagnosed WPW pattern on ECG (56% male; mean age at diagnosis 13.9 ± 2.5 years). EP were observed to have a significantly higher rate of guideline concordance than PC (95% vs. 71%, p < 0.001). There was significant practice variation between PC and EP in the documentation of a discussion of SCD risk: 96% in EP vs. 39% in PC (p < 0.001). CONCLUSION: Significant practice variation exists in the non-invasive and invasive risk stratification of pediatric WPW, with lower concordance to published guidelines amongst PC, when compared to EP. This report highlights the need to promote awareness of current WPW guidelines in the pediatric cardiology community at large.

Transcatheter Leadless Pacing in Children: A PACES Collaborative Study in the Real-World Setting.

BACKGROUND: Transcatheter Leadless Pacemakers (TLP) are a safe and effective option for adults with pacing indications. These devices may be an alternative in pediatric patients and patients with congenital heart disease for whom repeated sternotomies, thoracotomies, or transvenous systems are unfavorable. However, exemption of children from clinical trials has created uncertainty over the indications, efficacy, and safety of TLP in the pediatric population. The objectives of this study are to evaluate clinical indications, procedural characteristics, electrical performance, and outcomes of TLP implantation in children. METHODS: Retrospective data were collected from patients enrolled in the Pediatric and Congenital Electrophysiology Society TLP registry involving 15 centers. Patients ≤21 years of age who underwent Micra (Medtronic Inc, Minneapolis, MN) TLP implantation and had follow-up of ≥1 week were included in the study. RESULTS: The device was successfully implanted in 62 of 63 registry patients (98%) at a mean age of 15±4.1 years and included 20 (32%) patients with congenital heart disease. The mean body weight at TLP implantation was 55±19 kg and included 8 patients ≤8 years of age and ≤30 kg in weight. TLP was implanted by femoral (n=55, 87%) and internal jugular (n=8, 12.6%) venous approaches. During a mean follow-up period of 9.5±5.3 months, there were 10 (16%) complications including one cardiac perforation/pericardial effusion, one nonocclusive femoral venous thrombus, and one retrieval and replacement of TLP due to high thresholds. There were no deaths, TLP infections, or device embolizations. Electrical parameters, including capture thresholds, R wave sensing, and pacing impedances, remained stable. CONCLUSIONS: Initial results from the Pediatric and Congenital Electrophysiology Society TLP registry demonstrated a high level of successful Micra device implants via femoral and internal venous jugular approaches with stable electrical parameters and infrequent major complications. Long-term prospective data are needed to confirm the reproducibility of these initial findings.

Association of Weight With Ablation Outcomes in Pediatric Wolff-Parkinson-White: Analysis of the NCDR IMPACT Registry.

BACKGROUND: Guidelines for electrophysiology study (EPS) and catheter ablation in Wolff-Parkinson-White (WPW) are age based, but size may be a more relevant factor in determination of outcomes. OBJECTIVES: The goal of this study was to evaluate the association of patient weight with outcomes of catheter ablation for pediatric WPW. METHODS: A multicenter retrospective cohort study was performed on children aged 1 to 21 years with WPW and first-time EPS from April 2016 to December 2019 recorded in the IMPACT (Improving Pediatric and Adult Congenital Treatment) registry, excluding those with congenital heart disease, cardiomyopathy, and >1 ablation target. A weight threshold of 30 kg was selected, representing 1 SD below the cohort mean. The primary outcome was major adverse events (MAEs); additional outcomes included deferred ablation, use of cryoablation, and ablation success. RESULTS: A total of 4,456 subjects from 84 centers were evaluated, with 14% weighing <30 kg. Subjects weighing <30 kg were more likely to have preprocedural supraventricular tachycardia (45% vs 29%; P < 0.001) and less likely to have right septal accessory pathways (25% vs 33%; P < 0.001). MAEs were rare, although with higher incidence in the <30 kg cohort (0.3% vs 0.05%; P = 0.04). No difference was seen in likelihood of deferred ablation (9% vs 12%; P = 0.07) or use of cryoablation (11% vs 11%; P = 0.70). Success was higher in the <30 kg cohort: 95% vs 92% (P = 0.009). This effect persisted after adjusting for covariates (odds ratio: 1.6; 95% CI: 1.01-2.70; P = 0.046). CONCLUSIONS: Weight <30 kg was associated with a small but elevated risk of MAEs. Rates of deferred ablation and cryoablation were similar. Adjusting for factors (including accessory pathway type and location), weight <30 kg remained an independent predictor of acute success.

Natural history of TANGO2 deficiency disorder: Baseline assessment of 73 patients.

PURPOSE: TANGO2 deficiency disorder (TDD), an autosomal recessive disease first reported in 2016, is characterized by neurodevelopmental delay, seizures, intermittent ataxia, hypothyroidism, and life-threatening metabolic and cardiac crises. The purpose of this study was to define the natural history of TDD. METHODS: Data were collected from an ongoing natural history study of patients with TDD enrolled between February 2019 and May 2022. Data were obtained through phone or video based parent interviews and medical record review. RESULTS: Data were collected from 73 patients (59% male) from 57 unrelated families living in 16 different countries. The median age of participants at the time of data collection was 9.0 years (interquartile range = 5.3-15.9 years, range = fetal to 31.8 years). A total of 24 different TANGO2 alleles were observed. Patients showed normal development in early infancy, with progressive delay in developmental milestones thereafter. Symptoms included ataxia, dystonia, and speech difficulties, typically starting between the ages of 1 to 3 years. A total of 46/71 (65%) patients suffered metabolic crises, and of those, 30 (65%) developed cardiac crises. Metabolic crises were significantly decreased after the initiation of B-complex or multivitamin supplementation. CONCLUSION: We provide the most comprehensive review of natural history of TDD and important observational data suggesting that B-complex or multivitamins may prevent metabolic crises.

Impact of Device Miniaturization on Insertable Cardiac Monitor Use in the Pediatric Population: An Analysis of the MarketScan Commercial and Medicaid Databases.

Background Insertable cardiac monitors (ICMs) are effective in the detection of paroxysmal arrhythmias. In 2014, the first miniaturized ICM was introduced with a less invasive implant technique. The impact of this technology on ICM use in pediatric patients has not been evaluated. We hypothesized an increase in annual pediatric ICM implants starting in 2014 attributable to device miniaturization. Methods and Results A retrospective observational study was conducted using administrative claims from MarketScan Medicaid and commercial insurance claims databases. Use of ICM between January 2013 and December 2018 was measured (normalized to the total enrolled population ≤18 years) and compared with balancing measures (Holter ambulatory monitors, cardiac event monitors, encounters with syncope diagnosis, implantation of implantable cardioverter-defibrillator/pacemaker). Secondary analyses included evaluations of subsequent interventions and complications. The study cohort included 33 532 185 individual subjects, of which 769 (0.002%) underwent ICM implantation. Subjects who underwent ICM implantation were 52% male sex, with a median age of 16 years (interquartile range, 10-17 years). A history of syncope was present in 71%, palpitations in 43%, and congenital heart disease in 28%. Following release of the miniaturized ICM, use of ICMs increased from 5 procedures per million enrollees in 2013 to 11 per million between 2015 and 2018 (P<0.001), while balancing measures remained static. Of 394 subjects with ≥1 year of follow-up after implantation, interventions included catheter ablation in 24 (6%), pacemaker implantation in 15 (4%), and implantable cardioverter-defibrillator implantation in 7 (2%). Conclusions Introduction of the miniaturized ICM was followed by a rapid increase in pediatric use. The effects on outcomes and value deserve further attention.

Lymphatic cells do not functionally integrate into 3D organotypic brain slice cultures, but aggregate around penetrating blood vessels.

Brain slice culture (BSC) is a well-known three-dimensional model of the brain. In this study, we use organotypic slices for studying neuro-lymphatic physiology, to directly test the longstanding assumption that the brain is not a hospitable milieu for typical lymphatic vessels. An additional objective is to model fluid egress through brain perivascular space systems and to visualize potential cellular interactions among cells in the leptomeninges including alterations of cellular geometry and number of processes. Immortalized lymphatic rat cell lines were used to seed organotypic brain slices. The brain slice model was characterized by monitoring morphologies, growth rates, degree of apoptosis, and transport properties of brain slices with or without a lymphatic component. The model was then challenged with fibroblast co-cultures, as a control cell that is not normally found in the brain. Immortalized lymphatic cells penetrated the brain slices within 2-4 days. Typical cell morphology is spindly with bipolar and tripolar forms well represented. Significantly more indigo carmine marker passed through lymphatic seeded BSCs compared to arachnoid BSCs. Significantly more indigo carmine passed through brain slices co-cultured with fibroblast compared to lymphatic and arachnoid BSCs alone. We have developed an organotypic model in which lymphatic cells are able to interact with parenchymal cells in the cerebrum. Their presence appears to alter the small molecule transport ability of whole-brain slices. Lymphatic cells decreased dye transport in BSCs, possibly by altering the perivascular space. Given their direct contact with the CSF, they may affect convectional and diffusional processes. Our model shows that a decrease in lymphatic cell growth may reduce the brain slice's transport capabilities.

Cardiac crises: Cardiac arrhythmias and cardiomyopathy during TANGO2 deficiency related metabolic crises.

BACKGROUND: TANGO2 deficiency disorder (TDD) is an autosomal recessive disease associated with metabolic crisis, lethal cardiac arrhythmias, and cardiomyopathy. Data regarding treatment, management, and outcomes of cardiac manifestations of TDD are lacking. OBJECTIVE: The purpose of this study was to describe TDD-related cardiac crises. METHODS: Retrospective multicenter chart review was made of TDD patients admitted with cardiac crises, defined as development of ventricular tachycardia (VT), cardiomyopathy, or cardiac arrest during metabolic crises. RESULTS: Twenty-seven children were admitted for 43 cardiac crises (median age 6.4 years; interquartile range [IQR] 2.4-9.8 years) at 14 centers. During crisis, QTc prolongation occurred in all (median 547 ms; IQR 504-600 ms) and a type I Brugada pattern in 8 (26%). Arrhythmias included VT in 21 (78%), supraventricular tachycardia in 3 (11%), and heart block in 1 (4%). Nineteen patients (70%) developed cardiomyopathy, and 20 (74%) experienced a cardiac arrest. There were 10 deaths (37%), 6 related to arrhythmias. In 5 patients, recalcitrant VT occurred despite use of antiarrhythmic drugs. In 6 patients, arrhythmias were controlled after extracorporeal membrane oxygenation (ECMO) support; 5 of these patients survived. Among 10 patients who survived VT without ECMO, successful treatment included intravenous magnesium, isoproterenol, and atrial pacing in multiple cases and verapamil in 1 patient. Initiation of feeds seemed to decrease VT events. CONCLUSION: TDD-related cardiac crises are associated with a high risk of arrhythmias, cardiomyopathy, cardiac arrest, and death. Although further studies are needed, early recognition and appropriate treatment are critical. Acutely, intravenous magnesium, isoproterenol, atrial pacing, and ECMO as a last resort seem to be the best current treatment options, and early initiation of feeds may prevent VT events.

Relation of Norwood Shunt Type and Frequency of Arrhythmias at 6 Years (from the Single Ventricle Reconstruction Trial).

The Norwood procedure with a right ventricular to pulmonary artery shunt (RVPAS) decreases early mortality, but requires a ventriculotomy, possibly increasing risk of ventricular arrhythmias (VAs) compared with the modified Blalock-Taussig shunt (MBTS). The effect of shunt and Fontan type on arrhythmias by 6 years of age in the SVRII (Single Ventricle Reconstruction Extension Study) was assessed. SVRII data collected on 324 patients pre-/post-Fontan and annually at 2 to 6 years included antiarrhythmic medications, electrocardiography (ECG) at Fontan, and Holter/ECG at 6 years. ECGs and Holters were reviewed for morphology, intervals, atrioventricular conduction, and arrhythmias. Isolated VA were seen on 6-year Holter in >50% of both cohorts (MBTS 54% vs RVPAS 60%), whereas nonsustained ventricular tachycardia was rare and observed in RVPAS only (2.7%). First-degree atrioventricular block was more common in RVPAS than MBTS (21% vs 8%, p = 0.01), whereas right bundle branch block, QRS duration, and QTc were similar. Antiarrhythmic medication usage was common in both groups, but most agents also supported ventricular function (e.g., digoxin, carvedilol). Of the 7 patients with death or transplant between 2 and 6 years, none had documented VAs, but compared with transplant-free survivors, they had somewhat longer QRS (106 vs 93 ms, p = 0.05). Atrial tachyarrhythmias varied little between MBTS and RVPAS but did vary by Fontan type (lateral tunnel 41% vs extracardiac conduit 29%). VAs did not vary by Fontan type. In conclusion, at 6-year follow-up, benign VAs were common in the SVRII population. However, despite the potential for increased VAs and sudden death in the RVPAS cohort, these data do not support significant differences or increased risk at 6 years. The findings highlight the need for ongoing surveillance for arrhythmias in the SVR population.

Incidence of life-threatening events in children with Wolff-Parkinson-White syndrome: Analysis of a large claims database.

BACKGROUND: Previous estimates of life-threatening event (LTE) risk in Wolff-Parkinson-White (WPW) syndrome are limited by selection bias inherent to tertiary care referral-based cohorts. OBJECTIVE: This analysis sought to measure LTE incidence in children with WPW syndrome in a large contemporary representative population. METHODS: A retrospective cohort study was conducted using claims data from the IBM MarketScan Research Databases, evaluating subjects with WPW syndrome (age 1-18 years) from any encounter between January 1, 2013, and December 31, 2018. Subjects with congenital heart disease and cardiomyopathy were excluded. The primary outcome was diagnosis of ventricular fibrillation (VF); a composite outcome, LTE, was defined as occurrence of VF and/or cardiac arrest. VF and LTE rates were compared to matched representative controls without WPW syndrome (3:1 ratio). RESULTS: The prevalence of WPW syndrome was 0.03% (8733/26,684,581) over a median follow-up of 1.6 years (interquartile range 0.7-2.9 years). Excluding congenital heart disease/cardiomyopathy, 6946 subjects were analyzed. An LTE occurred in 49 subjects (0.7%), including VF in 20 (0.3%). The incidence of VF was 0.8 events per 1000 person-years, and the incidence of LTE was 1.9 events per 1000 person-years. There were no occurrences of VF in controls; the rate of LTE was 70 times higher in subjects with WPW syndrome (0.7%; 95% confidence interval 0.5%-0.9%) than in controls (0.01%; 95% confidence interval 0%-0.02%). CONCLUSION: The use of a large claims data set allowed for an evaluation of VF and LTE risk in an unselected pediatric population with WPW syndrome. The observed range of 0.8-1.9 events per 1000 person-years is consistent with prior reports from selected populations. A comparison of event rates to matched controls confirms and quantifies the significant elevation in VF and LTE risk in pediatric WPW syndrome.

Prevalent pharmacotherapy of US Fontan survivors: A study utilizing data from the MarketScan Commercial and Medicaid claims databases.

BACKGROUND: Survivors of Fontan palliation are at life-long risk of thrombosis, arrhythmia, and circulatory failure. To our knowledge, no studies have evaluated current United States pharmaceutical prescription practice in this population. METHODS: A retrospective observational study evaluating the prevalent use of prescription medications in children and adolescents with hypoplastic left heart syndrome or tricuspid atresia after Fontan completion (identified using ICD9/10 codes) was performed using data contained in the MarketScan Commercial and Medicaid databases for the years 2013 through 2018. Cardiac pharmaceuticals were divided by class. Anticoagulant agents other than platelet inhibitors, which are not uniformly a prescription medication, were also studied. Associations between increasing age and the likelihood of a filled prescription for each class of drug were evaluated. Annualized retail costs of pharmaceutical regimens were calculated. RESULTS: A cohort of 4,056 subjects (median age 12 years [interquartile range: 8-16], 61% male, 60% commercial insurance) was identified. Of the cohort, 50% received no prescription medications. Angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) (38%), diuretics (15%), and mineralocorticoid receptor antagonists (8%) were prescribed with the highest frequency. Pulmonary vasodilators were received by 6% of subjects. Older age was associated with increased likelihood of filled prescriptions for anticoagulants (P = .008), antiarrhythmic agents, digoxin, ACEi/ARB, and beta blockers (each P < .0001), but also lower likelihood of filled prescriptions for pulmonary vasodilators, conventional diuretics (both P < .0001), and mineralocorticoid receptor antagonists (P = .02). CONCLUSIONS: Pharmaceuticals typically used to treat heart failure and pulmonary hypertension are the most commonly prescribed medications following Fontan palliation. While the likelihood of treatment with a particular class of medication is associated with the age of the patient, determining the optimal regimen for individual patients and the population at large is an important knowledge gap for future research.