Spectrum of Viral Pathogens Identified in Children with Clinical Myocarditis (Pre-Coronavirus Disease-2019, 2000-2018): Etiologic Agent Versus Innocent Bystander.

OBJECTIVE: To identify the etiologies of viral myocarditis in children in the pre-coronavirus disease 2019 era. STUDY DESIGN: This was a retrospective review of all patients (age <18 years) diagnosed with myocarditis and hospitalized at Rady Children's Hospital San Diego between 2000 and 2018. RESULTS: Twenty-nine patients met inclusion criteria. Of 28 (97%) patients who underwent testing for viruses, polymerase chain reaction was used in 24 of 28 (86% of cases), and 16 of 24 (67%) detected a virus. Pathogens were rhinovirus (6), influenza A/B (4), respiratory syncytial virus (RSV) (3), coronavirus (3), parvovirus B19 (2), adenovirus (2), and coxsackie B5 virus, enterovirus, and parainfluenza virus type 2 in one case each. Six (21%) patients had no pathogen detected but imaging and other laboratory test results were compatible with myocarditis. Age 0-2 years was associated with RSV, influenza A/B, coronavirus, and enteroviruses (P < .001). Twenty-one patients (72%) experienced full clinical recovery. Three patients (10%) required venoarterial extracorporeal membrane oxygenation (VA-ECMO), and all 3 recovered. Three others (10%) required and underwent successful cardiac transplantation without complications. Two patients (7%) died 9-10 days after hospitalization (1 had RSV and 1 had influenza A/B). Two other patients presented with complete atrioventricular block; 1 case (rhinovirus) resolved spontaneously, and 1 (coronavirus) resolved after support with VA-ECMO. Age <2 years, female sex, lower ejection fraction at admission, and greater initial and peak levels of brain natriuretic peptide were significant predictors of critical outcomes (use of VA-ECMO, listing for cardiac transplantation, and death). CONCLUSIONS: Viral nucleic acid-based testing revealed a wider spectrum of viruses that could be associated with myocarditis in children than previously reported and traditionally anticipated. A predilection of certain pathogens in the very young patients was observed. Whether the observed range of viral agents reflects an undercurrent of change in viral etiology or viral detection methods is unclear, but the wider spectrum of viral pathogens found underscores the usefulness of polymerase chain reaction testing to explore possible viral etiologies of myocarditis in children.

Transjugular liver biopsy for Fontan associated liver disease surveillance: Technique, outcomes and hemodynamic correlation.

BACKGROUND: Fontan associated liver disease (FALD) is attributed to the limitations of the Fontan circulation, resulting in congestive hepatopathy. The technique and outcomes of transjugular liver biopsies (TJLB) in Fontan patients warrant definition as part of a rigorous FALD surveillance program. METHOD: Four year review of patients with Fontan physiology who underwent a TJLB during surveillance catheterizations. Biopsy site, technique, histology, angiography, hemodynamics, and complications were reviewed to assess correlation of biopsy scores with simultaneously obtained catheterization hemodynamics. RESULTS: 125 patients with a TJLB from 10/1/14 to 5/1/18. Median age 17 years (2-50.5). Technical success 100% (125/125), all samples diagnostic. 17% (21) accessed via the left internal jugular vein, secondary to right IJ occlusion or Heterotaxy syndrome. No patients had superior compartment obstruction preventing transjugular approach. 3.2% complication rate (4/125). Complications were early in the experience, including capsular perforation (2), renal hematoma (1) and hemobilia (1), all without long-term effect and all avoidable. After standardized entry/exit angiography was adopted, no further complications noted. There is a significant correlation between the newly described modified Ishak congestive hepatic fibrosis (ICHF) score with mean Fontan pressure, time from Fontan and cardiac index. CONCLUSIONS: TJLB is an alternate method for obtaining critical FALD surveillance data, with lower complication rates that traditional techniques. Vascular anomalies in Fontan physiology appear common and warrant pre-biopsy assessment. There is a significant correlation between biopsy score, time from Fontan, mean Fontan pressure and cardiac index.

Intravenous Sotalol in the Young: Safe and Effective Treatment With Standardized Protocols.

OBJECTIVES: This study assessed the safety and efficacy of novel and standardized protocols for the use of intravenous (IV) sotalol in pediatric patients. BACKGROUND: Acute arrhythmia treatments in children remain limited. IV sotalol is a new option but pediatric experience is limited. There is no standardized protocol for rapid infusion during acute arrhythmias. This study assessed a single center's initial experience with IV sotalol in young patients, describing a protocol for rapid infusion for acute treatment, and reviewed the safety and efficacy of maintenance dosing. METHODS: This is a retrospective study of all patients who received IV sotalol at Rady Children's Hospital. Demographics, arrhythmia, hemodynamics, and effects of IV sotalol were assessed. RESULTS: Thirty-seven patients received IV sotalol from December 2015 to December 2018. Group 1 (n = 26) received sotalol for acute therapy and group 2 (n = 11) received a maintenance dose of sotalol after successful cardioversion with alternate therapies. The groups had similar demographics. Group 1 included patients with atrial flutter (n = 16), patients with supraventricular tachycardia (SVT) (n = 9), and patients with atrial ectopic tachycardia (AET) (n = 1). All 9 patients with SVT (100%) converted to sinus rhythm after failure to convert using adenosine. Median administration time was 15 min, the median dose was 30 mg/m2, and mean time to cardioversion was 14 min. Group 2 median infusion time was 120 min, the median dose was 54 mg/m2/day, and all patients maintained sinus rhythm. No patients required cessation for adverse effects previously described for IV sotalol. CONCLUSIONS: IV sotalol was safe and effective for acute and maintenance therapy in young patients. In acute patients, 30 mg/m2 over 15 min converted most patients. IV sotalol adds a valuable option to IV therapies in the young.

Rapid Whole Genome Sequencing Has Clinical Utility in Children in the PICU.

OBJECTIVES: Genetic disorders are a leading contributor to mortality in the neonatal ICU and PICU in the United States. Although individually rare, there are over 6,200 single-gene diseases, which may preclude a genetic diagnosis prior to ICU admission. Rapid whole genome sequencing is an emerging method of diagnosing genetic conditions in time to affect ICU management of neonates; however, its clinical utility has yet to be adequately demonstrated in critically ill children. This study evaluates next-generation sequencing in pediatric critical care. DESIGN: Retrospective cohort study. SETTING: Single-center PICU in a tertiary children's hospital. PATIENTS: Children 4 months to 18 years admitted to the PICU who were nominated between July 2016 and May 2018. INTERVENTIONS: Rapid whole genome sequencing with targeted phenotype-driven analysis was performed on patients and their parents, when parental samples were available. MEASUREMENTS AND MAIN RESULTS: A molecular diagnosis was made by rapid whole genome sequencing in 17 of 38 children (45%). In four of the 17 patients (24%), the genetic diagnoses led to a change in management while in the PICU, including genome-informed changes in pharmacotherapy and transition to palliative care. Nine of the 17 diagnosed children (53%) had no dysmorphic features or developmental delay. Eighty-two percent of diagnoses affected the clinical management of the patient and/or family after PICU discharge, including avoidance of biopsy, administration of factor replacement, and surveillance for disorder-related sequelae. CONCLUSIONS: This study demonstrates a retrospective evaluation for undiagnosed genetic disease in the PICU and clinical utility of rapid whole genome sequencing in a portion of critically ill children. Further studies are needed to identify PICU patients who will benefit from rapid whole genome sequencing early in PICU admission when the underlying etiology is unclear.

Evaluation of Fontan liver disease: Correlation of transjugular liver biopsy with magnetic resonance and hemodynamics.

INTRODUCTION: Liver fibrosis and cirrhosis are late complications in Fontan palliation. Liver biopsy is the gold standard. The goal of this study is to correlate transjugular liver biopsy (TJLB) in the setting of Fontan palliation with noninvasive testing and hemodynamics. METHODS: Between August 2014 and July 2017, 49 Fontan patients underwent TJLB. All the patients had hemodynamic evaluation, 28 patients had MRE (magnetic resonance elastography) and 40 patients had cardiopulmonary exercise test. Histologic liver fibrosis was quantitated using traditional histologic scoring systems and a modified Ishak congestive hepatic fibrosis score. RESULTS: Median age 17.8 years, median time since Fontan 15.2 years. Primary diagnosis and Fontan type were variables, but predominantly LV morphology (30/49), lateral tunnel Fontan (29/49), originally fenestrated (37/49), and 11/49 had a pacemaker. Histologic fibrosis correlated with MRE (R = 0.62, P ≤ .001). Histologic fibrosis and MRE correlated with Fontan pressure (R = 0.38, P = .008 & R = 0.59, P ≤ .001). Morphology of the single ventricle did not correlate with liver fibrosis. The presence of a fenestration resulted in a higher cardiac index (P = .026) but did not resulted in lower liver fibrosis (P = .64). CONCLUSION: Noninvasive tests, such as MRE, may be suitable for longitudinal follow-up in patients with single ventricle physiology. Our data suggest that there is reasonable correlation of MRE liver stiffness with biopsy scoring systems and Fontan pressures. We demonstrated the feasibility of TJLB in the setting of Fontan palliation and demonstrated its correlation with noninvasive measures particularly MRE. We recommend selective use of TJLB when MRE score is >5 KPa or when there are other clinical signs of cirrhosis.

Catheter Ablation of Ventricular Arrhythmia for Ebstein's Anomaly in Unoperated and Post-Surgical Patients.

OBJECTIVES: The purpose of this study was to determine the ventricular arrhythmia (VA) substrates in patients with unoperated and post-surgical Ebstein's Anomaly (EA). BACKGROUND: EA is associated with variable atrialization of the right ventricle and a propensity for VA and sudden death. There are scant data on catheter ablation for VA in this population. METHODS: This was a retrospective study involving 11 congenital heart disease centers. RESULTS: A total of 24 patients (median age 17 [interquartile range (IQR): 11 to 37] years; age range 1 to 68 years; 42% men) with EA undergoing catheter ablation were identified. Prior tricuspid valve (TV) surgery had been performed in 12 (50%). Presenting symptoms were palpitations in 15, syncope in 4, aborted cardiac arrest in 4, and none in 1. At procedure, 28 VA substrates were encountered and 25 were completely characterized (median 1 per patient; cycle length 305 [IQR: 268 to 400] ms). In 3 cases, premature ventricular contraction (PVC) foci were targeted (1 with a history of PVC-induced ventricular fibrillation). VA mechanisms were focal in 15 and macro-re-entrant in 10, and did not differ significantly between those with and those without prior TV surgery (p = 0.7). Focal VAs predominantly localized to the atrialized right ventricle ARV in unoperated patients and to diseased myocardium or Purkinje tissue after TV surgery. Macro-re-entry was related to isolated scar or split potentials in the ARV in unoperated patients, and larger, more diffuse scar after TV surgery. Complete success was achieved in 22 (92%). There were 2 of 13 complications in patients <18 years of age and none in patients >18 years of age. There was a single recurrence over a median follow-up of 3.4 years. CONCLUSIONS: VA in EA may be either focal or macro-re-entrant. In the absence of surgery, substrates chiefly involve the ARV. After surgery, focal VA involves injured myocardium or Purkinje tissue and re-entrant ventricular tachycardia is related to post-surgical scar. Catheter ablation is a reasonable therapeutic approach for these patients.

Epicardial Intraoperative Three-Dimensional Mapping of Wolff-Parkinson-White Syndrome in a Child With Ebstein's Anomaly.

Catheter ablation of arrhythmias in small patients has inherent significant risk because of the patient, catheter, and lesion size. Heart block, perforation, and coronary damage may occur. This report shows adaptation of a three-dimensional electroanatomic mapping system for intraoperative use in a small patient with Ebstein's anomaly who was undergoing a cone procedure and a bidirectional Glenn procedure. Use of this technique gave clear identification of the epicardial insertion points of two accessory pathways causing Wolff-Parkinson-White syndrome and resistant episodes of supraventricular tachycardia. Successful three-dimensional mapping and cryoablation were performed with a short procedure time and no complications. The patient remains without preexcitation or arrhythmia 6 months postoperatively.

Intraoperative Three-Dimensional Mapping of Supraventricular Tachycardia in a Young Fontan Patient.

Preoperative tachycardia is uncommon before an initial Fontan procedure. Catheter intervention can risk complications in small patients. A patient with fetal tachycardia and double inlet left ventricle underwent Norwood and bidirectional Glenn procedures. She had persistent tachycardia. A three-dimensional electroanatomic mapping system was modified for the operative procedure; it was used to identify the arrhythmia substrate and cryoablate an atrioventricular nodal tachycardia. Mapping added 20 minutes to the operation. She is arrhythmia-free and off medication after 4 months. This three-dimensional system was successfully adapted for an intraoperative SVT ablation in this small patient, and it may be useful in other settings.

A Novel Method for Epicardial Defibrillator Lead Placement in Young Children: Coil Between the Great Arteries.

The primary and secondary prevention of sudden cardiac death resulting from malignant arrhythmia, channelopathy, and hypertrophic cardiomyopathy often requires the implantation of automatic internal cardiac defibrillators (AICDs) in the pediatric population. In young patients, the small size of the systemic veins, complex anatomy of congenital heart disease, and body habitus often preclude safe and durable transvenous placement of the AICD coil, requiring innovative methods to circumvent this problem. This report describes the technique used at Rady Children's Hospital San Diego/UCSD for the epicardial placement of an ICD system with a transvenous ICD coil placed between the aorta and pulmonary artery, thereby producing a stable location and excellent coil-to-can vector for successful defibrillation.

Sudden cardiac death and malignant arrhythmias: the scope of the problem in adult congenital heart patients.

A key component of recognizing sudden cardiac death (SCD) risk in the adult congenital heart disease (ACHD) patient is the recognition of heart failure risk for each physiology. The risk of SCD is an accrued phenomenon, representing the influences of anatomy, genetics, surgical and catheter interventions, and long-term sequelae of residual hemodynamic issues. These all lead to a substrate for tachyarrhythmia. It is beneficial in thinking about all of the potential combinations of CHD anatomy and physiologies to categorize SCD risk for the ACHD patient in terms of systemic left-ventricular failure, systemic right-ventricular failure, subpulmonary ventricular failure, the dyssynchronous contractility states due to bundle branch block, and single-site ventricular pacing. This article reviews important issues in arrhythmogenesis for ACHD patients with all of these physiologies and discusses potential cardiac rhythm device-management needs.