Oral Albuterol Treatment in Three Pediatric Patients with Bradycardia: A Novel Therapy.

Clinically significant bradycardia is an uncommon problem in children, but one that can cause significant morbidity and sometimes necessitates implantation of a pacemaker. The most common causes of bradycardia are complete heart block (CHB), which can be congenital or acquired, and sinus node dysfunction, which is rare in children with structurally normal hearts. Pacemaker is indicated as therapy for the majority of children with CHB, and while early mortality is lower in postnatally diagnosed CHB than in fetal CHB, it is still up to 16%. In young children, less invasive transvenous pacemaker systems can be technically challenging to place and carry a high risk of complications, often necessitating surgical epicardial pacemaker placement, which usually entails a median sternotomy. We report three cases of pediatric patients referred for pacemaker implantation for different types of bradycardia, treated at our institution with oral albuterol with therapeutic results that avoided the need for surgical pacemaker implantation at that time.

Long-Term Follow-Up of Second-Degree Heart Block in Children.

Little is known about the outcomes of children with second-degree heart block. We aimed to determine whether children with structurally normal hearts and Mobitz 1, 2:1 block or Mobitz 2 are at increased risk for progressing to complete heart block (CHB) or requiring a pacemaker (PM) at long-term follow-up. We searched our institutional electrophysiology database for children with potentially concerning second-degree block on ambulatory rhythm monitoring between 2009 and 2021, defined as frequent episodes of Mobitz 1 or 2:1 block, episodes of Mobitz 1 or 2:1 block with additional evidence of conduction disease (i.e. first-degree heart block, bundle branch block), or episodes of Mobitz 2. Ambulatory rhythm monitor, ECG, and demographic data were reviewed. The primary composite outcome was CHB on follow-up rhythm monitor or PM placement. 20 patients were in the final analysis. Six (30%) patients either developed CHB but do not have a PM (4 = 20%) or have a PM (2 = 10%). Median follow-up was 5.8 years (IQR 4.4-7.0). Patients with CHB or PM were more likely to have second-degree block at maximum sinus rate (67% vs. 0%, p = 0.003), a below normal average heart rate (67% vs. 14%, p = 0.04), and 2:1 block on initial ECG (50% vs. 0%, p = 0.02). In this study of children with potentially concerning second-degree block, 30% of patients progressed to CHB or required a PM. Second-degree block at maximum sinus rate, a low average heart, and 2:1 block on initial ECG were associated with increased risk of disease progression.

Assessing the utility of atrial fibrillation induction to risk stratify children with Wolff-Parkinson-White syndrome.

BACKGROUND: Wolff-Parkinson-White syndrome is associated with sudden cardiac death from rapid conduction through the accessory pathway in atrial fibrillation. Adult patients are at higher risk for sudden cardiac death if the shortest-pre-excited-RR-interval in atrial fibrillation (SPERRI) is ≤250 milliseconds (msec) during electrophysiologic study. Exclusive conduction through the atrioventricular node in atrial fibrillation is presumed to convey lower risk. The shortest-pre-excited-paced-cycle-length with atrial pacing has also served as a marker for risk stratification. OBJECTIVE: To determine accessory pathway characteristic of patients undergoing induction of atrial fibrillation during electrophysiologic study. METHODS: We reviewed 321 pediatric patients that underwent electrophysiologic study between 2010 and 2019. Induction of atrial fibrillation was attempted on patients while on isoproterenol and SPERRI was measured if atrial fibrillation was induced. Shortest-pre-excited-paced-cycle-length (SPPCL) was determined while on isoproterenol. RESULTS: Atrial fibrillation was induced in 233 (73%) patients. Of those, 104 (45%) patients conducted exclusively through the atrioventricular node during atrial fibrillation (Group A). The remaining 129 (55%) patients had some conduction through the accessory pathway (Group B). In Group A, SPPCL was 260 msec with 48 (46%) conducting through the accessory pathway at ≤250 msec. In Group B, SPPCL was 240 msec with 92 patients (71%) conducting at ≤250 msec (p < 0.05). In Group B, SPERRI was 250 msec and had a positive correlation with SPPCL (p < 0.001, R2 = 0.28). Almost half (46%) of those with exclusive conduction through the atrioventricular node in atrial fibrillation had rapid accessory pathway conduction with atrial pacing. CONCLUSION: Conduction in atrial fibrillation during electrophysiologic study on isoproterenol via the atrioventricular node may not exclude high-risk accessory pathways in pediatric patients.

Comparison of AliveCor KardiaMobile Six-Lead ECG with Standard ECG in Pediatric Patients.

The AliveCor KardiaMobile (ACKM) is a remote electrocardiogram (ECG) monitoring device. Little research has been conducted on its accuracy with pediatric patients. This prospective study aims to compare the ACKM six-lead device with a standard fifteen-lead ECG in measuring the QTc, QRS, and axis in pediatric patients. Pediatric patients ages 5 to 21 years were enrolled prospectively to have their ECG recorded using an ACKM six-lead device following a recording with the standard 15-lead ECG. A pediatric electrophysiologist measured the QTc, QRS interval, and QRS axis for both ECGs. Bland-Altman analysis was performed to assess agreement among measurements. The study included 141 patients. The mean age was 12.3 ± 4.4 years. Average heart rate was 79 ± 16 bpm. The mean difference in the QTc measurements for a paired standard ECG and ACKM was - 0.6 ms [95% confidence interval - 48 to 47 ms]. Of the ACKM QTc measurements, 117 (83%) were within 30 ms of the standard ECG. The mean difference in paired QRS measurements was - 1.3 ms [95% confidence interval - 23 to 21 ms]. Of the ACKM QRS measurements, 134 (95%) were within 20 ms of the standard ECG. The measured axis was the same for 84% of ACKM and standard ECGs. Over 80% of the ACKM six-lead ECGs produced QTc, QRS, and axis deviation measurements within a clinically useful range of the standard ECG. However, it is not accurate enough to be used consistently in place of a standard ECG for QTc and QRS measurement for pediatric patients.

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.

Multicenter Outcomes of Catheter Ablation for Atrioventricular Reciprocating Tachycardia Mediated by Twin Atrioventricular Nodes.

OBJECTIVES: This study sought to describe the electrophysiologic properties and catheter ablation outcomes for atrioventricular reciprocating tacchycardia via twin atrioventricular nodes (T-AVRT). BACKGROUND: Although catheter ablation for T-AVRT is an established entity, there are few data on the electrophysiological properties and outcomes of this procedure. METHODS: An international, multicenter study was conducted to collect retrospective procedural and outcomes data for catheter ablation of T-AVRT. RESULTS: Fifty-nine patients with T-AVRT were identified (median age at procedure, 8 years [interquartile range: 4.4-17.0 years]; 49% male). Of these, 55 (93%) were diagnosed with heterotaxy syndrome (right atrial isomerism in 39, left atrial isomerism in 8, and indeterminate in 8). Twenty-three (39%) had undergone Fontan operation (12 extracardiac, 11 lateral tunnel). After the Fontan operation, atrial access was conduit or baffle puncture in 15 (65%), fenestration in 5 (22%), and retrograde in 3 (13%). Acute success was achieved in 43 (91%) of 47 attempts (targeting an anterior node in 23 and posterior node in 24). There was no high-grade AV block or change in QRS duration. Over a median of 3.8 years, there were 3 recurrences. Of 7 patients with failed index procedure or recurrent T-AVRT, 6 (86%) were associated with anatomical hurdles such as prior Fontan or catheter course through an interrupted inferior vena cava-to-azygous vein continuation (P = 0.11). CONCLUSIONS: T-AVRT can be targeted successfully with low risk for recurrence. Complications were rare in this population. Anatomical challenges were common among patients with reduced short and long-term efficacy, representing opportunities for improvement in procedural timing and planning.

Supraventricular Tachycardia Without Preexcitation as a Cause of Sudden Cardiac Arrest in Pediatric Patients.

Sudden cardiac arrest in pediatric patients is a rare occurrence. Supraventricular tachycardia without the presence of ventricular preexcitation in pediatric patients with a structurally normal heart is generally considered benign. Previous literature in adults reported a subset of patients in whom SVT was suspected to be the primary trigger of sudden cardiac arrest. We performed a single-center, retrospective cohort study of pediatric patients without known heart disease, 1-21 years of age, presenting with aborted SCA between 2009 and 2019. We collected diagnostic studies in all patients to identify the etiology of the aborted SCA. Thirty patients met the inclusion criteria. The median age at the time of SCA was 15.2 years. The etiology of SCA was identified in 23 (77%) patients. Of the seven patients with unknown diagnosis after initial diagnostic studies, three patients subsequently developed fast SVT that was presumed to be the etiology of the initial SCA. These three patients had varying diagnoses of atrioventricular nodal reentry tachycardia, ectopic atrial tachycardia, and a concealed accessory pathway with atrioventricular reentrant tachycardia. After ablation or medical treatment of the SVT substrate, no further tachyarrhythmias were observed. Pediatric patients presenting with an aborted SCA of unknown etiology ought to be considered for electrophysiology testing to elicit occult SVT substrates that may lead to a malignant ventricular tachyarrhythmia.

Anodal stimulation in pediatric patients with permanent epicardial ventricular pacemakers.

OBJECTIVES: We aimed to measure the frequency and factors associated with anodal stimulation in a pediatric population with epicardial pacing leads. BACKGROUND: In bipolar pacemakers, capture of the myocardium typically occurs at the cathode. However, AS with capture at the anode has been described. This has not been described in epicardial pacemakers. METHODS: Retrospective data were collected from patients ≤ 21 years of age with permanent bipolar epicardial ventricular pacemakers from 1/2017 to 1/2018. AS was defined as a clear change on surface ECG in at least one of the 12 leads assessed by two blinded pediatric electrophysiologists. RESULTS: Twenty-four bipolar leads in 23 patients were included in the study. One patient had both biventricular leads tested. Median age was 7.1 years (IQR 5.0-10.9), weight was 20.9 kg (IQR 16.5-33.5), and 65% were male. Testing was performed at a median of 2.8 years (IQR 1.6-6.1) after implant. Congenital heart disease was present in 57%. Complete heart block was the pacemaker indication in 78%. AS was identified in 16/24 (67%) of leads tested. Identification of AS was associated with presence of congenital heart disease (p = 0.004) and 3DD between electrodes (p = 0.04). CONCLUSIONS: AS is common in pediatric patients and was associated with a history of congenital heart disease and greater estimated 3DD between electrodes. The prevalent nature of AS may allow clinicians to utilize existing pacemakers as multisite pacing systems.

Conduction Properties and Ablation of Adenosine Sensitive Accessory Pathways in Children.

Block in accessory pathway (AP) conduction with adenosine has been previously described. However, conduction characteristics of these APs has not been well defined to date. All patients with APs

Bicontinuous Ion-Exchange Materials through Polymerization-Induced Microphase Separation.

Polymerization-induced microphase separation has been used to prepare solid cross-linked monoliths containing bicontinuous and nanostructured polymer domains. We use this process to fabricate a monolith containing either a negatively or positively charged polyelectrolyte domain inside of the neutral styrene/divinylbenzene-derived matrix. First, the materials are made with a neutral pre-ionic polymer containing masked charged groups. The monoliths are then functionalized to a charged state by treatment with trimethylamine; small-angle X-ray scattering shows no significant morphological change in the microphase-separated structure upon postpolymerization modification. By exchanging dyes with the counterions in the material, we corroborated the continuity of the charged domains. Using ion-exchange capacity measurements, we estimate the number of accessible charges within the material based on macro-chain transfer agent molar mass and loading.

Long-Term Patient Experience Following Acutely Successful Ablation of Supraventricular Tachycardia Substrate in Children.

Definitive treatment of supraventricular tachycardia (SVT) substrate involves catheter ablation. While objective success rates have been well established, long-term subjective patient experiences have not been well described. We quantify a subjective cure rate and characterize long-term patient experience after acutely successful ablation. A cross-sectional survey of pediatric patients with accessory pathways or atrioventricular nodal reentrant tachycardia who underwent acutely successful ablation from 2008 to 2012 was performed. Data were obtained from medical records and patient surveys. Patients with congenital heart disease other than patent ductus arteriosus, patent foramen ovale, or coronary artery abnormalities were excluded. Statistical analyses included Student's t-test and χ2 analysis for continuous and categorical variables, respectively. Surveys were sent to 153 patients of which 147 responded with median follow-up of 7.2 (IQR 6.1-8.5) years. Of the 147 responders, 124 (84%) patients reported cure with a male predominance. Symptoms were present in 130/147 (88%) patients pre-ablation and in 53/147 (36%) post-ablation. Among those with post-ablation symptoms, 50/53 (94%) reported symptomatic improvement. Recurrence occurred in 23/147 (16%) patients and was more prevalent following cryoablation. Ablation of SVT substrate can be curative with excellent long-term results and patient satisfaction. Long-term subjective cure rate is high and there is a substantial decrease in symptoms post-ablation. Many patients continue to have symptoms following ablation; however, the majority of these patients consider themselves cured and symptoms can be attributed to other etiologies. Recurrence is uncommon and occurs more frequently following cryoablation.

MIS-C and Cardiac Conduction Abnormalities.

OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) has spread through the pediatric population during the coronavirus disease 2019 pandemic. Our objective for the study was to report the prevalence of conduction anomalies in MIS-C and identify predictive factors for the conduction abnormalities. METHODS: We performed a single-center retrospective cohort study of pediatric patients <21 years of age presenting with MIS-C over a 1-month period. We collected clinical outcomes, laboratory findings, and diagnostic studies, including serial electrocardiograms, in all patients with MIS-C to identify those with first-degree atrioventricular block (AVB) during the acute phase and assess for predictive factors. RESULTS: Thirty-two patients met inclusion criteria. Median age at admission was 9 years. Six of 32 patients (19%) were found to have first-degree AVB, with a median longest PR interval of 225 milliseconds (interquartile range 200-302), compared with 140 milliseconds (interquartile range 80-178) in patients without first-degree AVB. The onset of AVB occurred at a median of 8 days after the initial symptoms and returned to normal 3 days thereafter. No patients developed advanced AVB, although 1 patient developed a PR interval >300 milliseconds. Another patient developed new-onset right bundle branch block, which resolved during hospitalization. Cardiac enzymes, inflammatory markers, and cardiac function were not associated with AVB development. CONCLUSIONS: In our population, there is a 19% prevalence of first-degree AVB in patients with MIS-C. All patients with a prolonged PR interval recovered without progression to high-degree AVB. Patients admitted with MIS-C require close electrocardiogram monitoring during the acute phase.

Anomalously Slow Conformational Change Dynamics of Polar Groups Anchored to Hydrophobic Surfaces in Aqueous Media.

Water molecules within a thin hydration layer, spontaneously generated on hydrophobic protein surfaces, are reported to form a poorly dynamic network structure. However, how such a water network affects the conformational change dynamics of polar groups has never been explored, although such polar groups play a critical role in protein-protein and protein-ligand interactions. In the present work, we utilized as model protein surfaces a series of self-assembled monolayers (SAMs) appended with polar (Fmoc) or ionic (FITC) fluorescent head groups that were tethered via a 1.5-nm-long flexible oligoether chain to a hydrophobic silicon wafer surface, which was densely covered with paraffinic chains. We found that, not only in deionized water but also in aqueous buffer, these oligoether-appended head groups at ambient temperatures both displayed an anomalously slow conformational change, which required ∼10 h to reach a thermodynamically equilibrated state. We suppose that these behaviors reflect the poorly dynamic and low-permittivity natures of the thin hydration layer.

COVID-19 reveals Brugada pattern in an adolescent patient.

A diagnosis of Brugada pattern in paediatric or adolescent patients is rare. COVID-19 is characterised by fevers and a pro-inflammatory state, which may serve as inciting factors for Brugada pattern. Recently described in two adult patients, we report the first case of Brugada pattern in an adolescent with COVID-19.

Cardiac workup and monitoring in hospitalised children with COVID- 19.

Approximately, 1.7 million individuals in the United States have been infected with SARS-CoV-2, the virus responsible for the novel coronavirus disease-2019 (COVID-19). This has disproportionately impacted adults, but many children have been infected and hospitalised as well. To date, there is not much information published addressing the cardiac workup and monitoring of children with COVID-19. Here, we share the approach to the cardiac workup and monitoring utilised at a large congenital heart centre in New York City, the epicentre of the COVID-19 pandemic in the United States.

Impact of dipyridamole on adenosine dosing in pediatric and young adult patients after heart transplantation.

BACKGROUND: Relative contraindications to adenosine use have included heart transplant and dipyridamole. We previously demonstrated the safety and efficacy of adenosine-induced atrioventricular (AV) block in healthy young heart transplant recipients while suspending dipyridamole therapy (dual antiplatelet agent). This prospective follow-up study evaluated the safety and efficacy of adenosine use in the same cohort of heart transplant recipients while on dipyridamole. METHODS: Adenosine was incrementally dosed until AV block occurred (maximum 200 mcg/kg up to 12 mg). The primary outcome was clinically significant asystole (≥12 seconds). Secondary outcomes included maximal adenosine dose, AV block duration, dysrhythmias, and clinical symptoms. Outcomes were compared to the parent study. RESULTS: Thirty of 39 eligible patients (5-24 years) were tested. No patient (0%, CI 0%-8%) experienced clinically significant asystole. AV block occurred in 29/30 patients (97%, CI 86%-100%). The median dose causing AV block was 50mcg/kg (vs 100 mcg/kg off dipyridamole; P = .011). Seventeen patients (57%, CI 39%-72%) required less adenosine to achieve AV block on dipyridamole; six (20%) required more. AV block occurred at doses ≥25 mcg/kg in all patients. In pairwise comparison to prior testing off dipyridamole, no significant change occurred in AV block duration, frequency of cardiac ectopy, or incidence of reported symptoms. No atrial fibrillation/flutter occurred. CONCLUSIONS: AV block often occurs at twofold lower adenosine doses in healthy young heart transplant recipients taking oral dipyridamole, compared with previous testing of this cohort off dipyridamole. Results suggest that initial dosing of 25 mcg/kg (maximum 0.8 mg) with stepwise escalation poses low risk of prolonged asystole on dipyridamole.

Comparison of Holter With Zio Patch Electrocardiography Monitoring in Children.

The standard for ambulatory arrhythmia detection in children is the Holter monitor. The Zio XT (Zio) patch has been FDA-approved for use in adults. However, its utility in children has not been directly compared with the Holter. We studied the ability to detect arrhythmias and patient comfort of the Zio versus the Holter in children. Patients <22 years old were prospectively enrolled to wear the Holter and Zio simultaneously for 48 hours at our institution. Detection of clinically significant arrhythmias was compared using McNemar's test. Wear-time and artifact time was compared using Wilcoxon sign test. Patient satisfaction ratings were analyzed with paired t tests. Two hundred patients (57% male) were included for analysis. The median age was 13.5 years (range 23 days to 21.7 years), and 40% had heart disease. The Zio and Holter had comparable median wear-times, 48.2 hours (interquartile range [IQR] 45.8 to 50.2]) versus 48.0 (48.0 to 48.0), respectively, p = 0.14, but the Zio had less artifact than the Holter, 2.8% (IQR 1.1 to 8.6) versus 5.6% (2.4 to 15.7), respectively, p <0.001. There was no difference in detection of clinically significant arrhythmias for the Zio versus the Holter (p = 0.23), however 75% of patients preferred the Zio over the Holter (p <0.001) due to lack of wires and the ability to shower. In conclusion, the Zio patch is as good as the Holter monitor in detection of clinically significant arrhythmias in children with less artifact. Patients/parents more often preferred the Zio over the Holter.

Localization of Accessory Pathways in Pediatric Patients With Wolff-Parkinson-White Syndrome Using 3D-Rendered Electromechanical Wave Imaging.

OBJECTIVES: This study sought to demonstrate the feasibility of electromechanical wave imaging (EWI) for localization of accessory pathways (AP) prior to catheter ablation in a pediatric population. BACKGROUND: Prediction of AP locations in patients with Wolff-Parkinson-White syndrome is currently based on analysis of 12-lead electrocardiography (ECG). In the pediatric population, specific algorithms have been developed to aid in localization, but these can be unreliable. EWI is a noninvasive imaging modality relying on a high frame rate ultrasound sequence capable of visualizing cardiac electromechanical activation. METHODS: Pediatric patients with ventricular pre-excitation presenting for catheter ablation were imaged with EWI immediately prior to the start of the procedure. Two clinical pediatric electrophysiologists predicted the location of the AP based on ECG. Both EWI and ECG predictions were blinded to the results of catheter ablation. EWI and ECG localizations were subsequently compared with the site of successful ablation. RESULTS: Fifteen patients were imaged with EWI. One patient was excluded for poor echocardiographic windows and the inability to image the entire ventricular myocardium. EWI correctly predicted the location of the AP in all 14 patients. ECG analysis correctly predicted 11 of 14 (78.6%) of the AP locations. CONCLUSIONS: EWI was shown to be capable of consistently localizing accessory pathways. EWI predicted the site of successful ablation more frequently than analysis of 12-lead ECG. EWI isochrones also provide anatomical visualization of ventricular pre-excitation. These findings suggest that EWI can predict AP locations, and EWI may have the potential to better inform clinical electrophysiologists prior to catheter ablation procedures.

3D-rendered Electromechanical Wave Imaging for Localization of Accessory Pathways in Wolff-Parkinson-White Minors.

Arrhythmia localization prior to catheter ablation is critical for clinical decision making and treatment planning. The current standard lies in 12-lead electrocardiogram (ECG) interpretation, but this method is non-specific and anatomically limited. Accurate localization requires intracardiac catheter mapping prior to ablation. Electromechanical Wave Imaging (EWI) is a high frame-rate ultrasound modality capable of non-invasively mapping the electromechanical activation in all cardiac chambers in vivo. In this study, we evaluate 3D-rendered EWI as a technique for consistently localizing the accessory pathway (AP) in Wolff-Parkinson-White (WPW) pediatric patients. A 2000 Hz EWI diverging sequence was used to transthoracically image 13 patients with evidence of ECG pre-excitation, immediately prior to catheter ablation and after successful ablation whenever possible. 3D-rendered activation maps were generated by co-registering and interpolating the 4 resulting multi-2D isochrones. A blinded electrophysiologist predicted the AP location on 12-lead ECG prior to ablation. Double-blinded EWI isochrones and clinician assessments were compared to the successful ablation site as confirmed by intracardiac mapping using a segmented template of the heart with 19 ventricular regions. 3D-rendered EWI was shown capable of consistently localizing AP in all the WPW cases. Clinical ECG interpretation correctly predicted the origin with an accuracy of 53.8%, respectively 84.6% when considering predictions in immediately adjacent segments correct. Our method was also capable of assessing the difference in activation pattern from before to after successful ablation on the same patient. These findings indicate that EWI could inform current diagnosis and expedite treatment planning of WPW ablation procedures.