Thromboembolism prophylaxis practices of pediatric and congenital electrophysiologists during invasive electrophysiology studies: A PACES survey.

BACKGROUND: Thromboembolic events related to invasive electrophysiology studies, while rare, can have devastating consequences. Use of systemic anticoagulation for a pediatric or adult-congenital invasive electrophysiology study is recommended, however there is no established standard of practice in this population. OBJECTIVE: To report on procedural practices for thromboembolism prophylaxis during invasive electrophysiology studies for pediatric patients and adults with congenital heart disease. METHODS: An anonymous web-based survey was sent to the members of the Pediatric and Congenital Electrophysiology Society. The survey focused on pre-procedural, intra-procedural, and post-procedural thromboembolism prophylaxis practices during invasive electrophysiology studies. Significant practice variation was defined as <90% concordance among respondents. RESULTS: Survey was completed by 73 members; 52 (71%) practicing in the United States, 65 (89%) practicing in an academic institution, and 14 (19%) in an institution that performs more than 200 invasive electrophysiology procedures annually. Responses showed significant variation in practice. Prior to an invasive electrophysiology procedure, 25% discontinue aspirin while 47% discontinue anticoagulants. Heparin is given for all procedures by 32%. When heparin is administered, the first dose is given by 32% after sheaths are placed, 42% after crossing into the systemic atrium, and 26% just prior to systemic-side ablation. Most target an activated clotting time between 200-300 seconds. Post systemic-side ablation, 58% do not initiate a heparin infusion. Post-procedural oral agents were initiated on day of procedure by 34% of respondents and on post-procedure day 1 by 53%. If treating with aspirin, 74% use low-dose (3-5 mg/kg or 81 mg daily), and 68% treat for 4-6 weeks. CONCLUSION: There is significant variation in thromboembolism prophylaxis for invasive EP studies among pediatric and congenital electrophysiologists. Further studies are needed to optimize the management of thromboembolism prophylaxis in this population.

Use of supra-therapeutic phenytoin for management of ventricular arrhythmias in children: Case series and literature review.

Phenytoin is a versatile drug with utility in neurological, dermatological, and even cardiac disease processes. Though phenytoin is widely available due to its excellent anti-epileptic properties, it is now rarely used as an antiarrhythmic. Phenytoin has well-studied sodium-channel blocking abilities which can be taken advantage of to treat ventricular arrhythmias. Thus, it should remain in the arsenal of antiarrhythmics for any electrophysiologist. We present two cases of intractable ventricular arrhythmia in children that were controlled with phenytoin at supra-therapeutic serum levels, preventing the need for heart transplantation.

Non-surgical treatment of congenital left ventricle to coronary sinus fistula and Wolf-Parkinson-White.

Congenital left ventricle to coronary sinus fistula is a rare entity. We report a case of an infant with prenatal finding of left ventricle to right atrial shunt. The anatomy was defined by multi-modality imaging. Baseline electrocardiogram was notable for a Wolff-Parkinson-White pattern. He underwent successful catheter device closure of the left ventricle to coronary sinus fistula. The patient developed supraventricular tachycardia and underwent successful ablation of the accessory pathway.

Lead Extraction at a Pediatric/Congenital Heart Disease Center: The Importance of Patient Age at Implant.

OBJECTIVES: This study sought to evaluate the safety and efficacy of transvenous lead extraction (TLE) at a single pediatric/congenital heart disease (CHD) center. BACKGROUND: Data on TLE in pediatric and CHD patients are limited. METHODS: Retrospective cohort study evaluating TLE from 2008 to 2019. RESULTS: A total of 113 patients underwent TLE with 162 leads removed (including 38 high-voltage leads). Median age at lead implantation was 13 years (range 0.6-61.8 years), with a median age at extraction of 21.6 years (6.4-64.3 years). Median lead age was 7.2 years (1.0-35.3 years). Successful extraction occurred in 110 (97%) patients, 159 (98%) leads. Complex extraction was needed for 120 leads; 52 (44%) using laser alone, 27 (23%) mechanical sheath alone, and 21 (18%) using both. Femoral extraction was used for 19 (16%) leads. Risk factors for complex extraction were ≥2 leads extracted (odds ratio: 3.36; 95% confidence interval [CI]: 1.2-9.36; P = 0.021), lead within the right ventricle (odds ratio: 2.8; 95% CI: 1.2-6.5; P = 0.017), and a combination of younger patient age at implant and older lead age at extraction, with patients ≤12 years of age at implant and leads ≥7 years of age having an odds ratio: of 10.1 (95% CI: 2.21-45.9; P = 0.003). Major complications occurred in 5 (4.4%) of patients, with no mortality, but a high incidence of tricuspid valve injury. CONCLUSIONS: TLE can be performed successfully and safely in a pediatric and CHD center. Patient age at lead implantation, not age at extraction, is an important predictor of needing a complex extraction, with younger patients at implant and older leads at extraction having the highest risk.

2021 PACES Expert Consensus Statement on the Indications and Management of Cardiovascular Implantable Electronic Devices in Pediatric Patients: Developed in collaboration with and endorsed by the Heart Rhythm Society (HRS), the American College of Cardiology (ACC), the American Heart Association (AHA), and the Association for European Paediatric and Congenital Cardiology (AEPC) Endorsed by the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS).

In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.

2021 PACES expert consensus statement on the indications and management of cardiovascular implantable electronic devices in pediatric patients.

In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.

2021 PACES Expert Consensus Statement on the Indications and Management of Cardiovascular Implantable Electronic Devices in Pediatric Patients.

In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.

2021 PACES expert consensus statement on the indications and management of cardiovascular implantable electronic devices in pediatric patients: Executive summary.

Guidelines for the implantation of cardiac implantable electronic devices (CIEDs) have evolved since publication of the initial ACC/AHA pacemaker guidelines in 1984 [1]. CIEDs have evolved to include novel forms of cardiac pacing, the development of implantable cardioverter defibrillators (ICDs) and the introduction of devices for long term monitoring of heart rhythm and other physiologic parameters. In view of the increasing complexity of both devices and patients, practice guidelines, by necessity, have become increasingly specific. In 2018, the ACC/AHA/HRS published Guidelines on the Evaluation and Management of Patients with Bradycardia and Cardiac Conduction Delay [2], which were specific recommendations for patients >18 years of age. This age-specific threshold was established in view of the differing indications for CIEDs in young patients as well as size-specific technology factors. Therefore, the following document was developed to update and further delineate indications for the use and management of CIEDs in pediatric patients, defined as ≤21 years of age, with recognition that there is often overlap in the care of patents between 18 and 21 years of age. This document is an abbreviated expert consensus statement (ECS) intended to focus primarily on the indications for CIEDs in the setting of specific disease/diagnostic categories. This document will also provide guidance regarding the management of lead systems and follow-up evaluation for pediatric patients with CIEDs. The recommendations are presented in an abbreviated modular format, with each section including the complete table of recommendations along with a brief synopsis of supportive text and select references to provide some context for the recommendations. This document is not intended to provide an exhaustive discussion of the basis for each of the recommendations, which are further addressed in the comprehensive PACES-CIED document [3], with further data easily accessible in electronic searches or textbooks.

2021 PACES expert consensus statement on the indications and management of cardiovascular implantable electronic devices in pediatric patients.

In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.

A distinct molecular mechanism by which phenytoin rescues a novel long QT 3 variant.

BACKGROUND: Genetic variants in SCN5A can result in channelopathies such as the long QT syndrome type 3 (LQT3), but the therapeutic response to Na+ channel blockers can vary. We previously reported a case of an infant with malignant LQT3 and a missense Q1475P SCN5A variant, who was effectively treated with phenytoin, but only partially with mexiletine. Here, we functionally characterized this variant and investigated possible mechanisms for the differential drug actions. METHODS: Wild-type or mutant Nav1.5 cDNAs were examined in transfected HEK293 cells with patch clamping and biochemical assays. We used computational modeling to provide insights into altered channel kinetics and to predict effects on the action potential. RESULTS: The Q1475P variant in Nav1.5 reduced the current density and channel surface expression, characteristic of a trafficking defect. The variant also led to positive shifts in the voltage dependence of steady-state activation and inactivation, faster inactivation and recovery from inactivation, and increased the "late" Na+ current. Simulations of Nav1.5 gating with a 9-state Markov model suggested that transitions from inactivated to closed states were accelerated in Q1475P channels, leading to accumulation of channels in non-inactivated closed states. Simulations with a human ventricular myocyte model predicted action potential prolongation with Q1475P, compared with wild type, channels. Patch clamp data showed that mexiletine and phenytoin similarly rescued some of the gating defects. Chronic incubation with mexiletine, but not phenytoin, rescued the Nav1.5-Q1475P trafficking defect, thus increasing mutant channel expression. CONCLUSIONS: The gain-of-function effects of Nav1.5-Q1475P predominate to cause a malignant long QT phenotype. Phenytoin partially corrects the gating defect without restoring surface expression of the mutant channel, whereas mexiletine restores surface expression of the mutant channel, which may explain the lack of efficacy of mexiletine when compared to phenytoin. Our data makes a case for experimental studies before embarking on a one-for-all therapy of arrhythmias.

Pseudopolymorphic Wide Complex Tachycardia in a Child With Long QT Syndrome.

Implantable loop recorders (ILRs) can be a valuable tool in monitoring patients with inherited arrhythmia. This paper reports on a family with long QT syndrome (type 2 [LQT2]) in which a pseudopolymorphic wide complex tachycardia detected by ILR was ultimately diagnosed as a supraventricular aberrant rhythm, facilitated by noncompliance with beta-blocker therapy. (Level of Difficulty: Intermediate.).

Outcomes of catheter ablation of anteroseptal and midseptal accessory pathways in pediatric patients.

BACKGROUND: Outcomes for catheter ablation of accessory pathways in pediatric patients have steadily improved, with the exception of pathways located in the anteroseptal (AS) and midseptal (MS) regions, where success is limited by the close proximity of normal atrioventricular conduction. OBJECTIVE: The purpose of this study was to evaluate the efficacy of different catheter approaches and ablation energy modalities used for catheter ablation at these sites. METHODS: A retrospective review was performed of all electrophysiology studies conducted between July 2001 and July 2017. Acute success and recurrence rates were assessed by comparing catheter approaches and energy modalities used for ablation. RESULTS: A total of 255 electrophysiology procedures were performed in 223 patients (178 AS, 72 MS, 5 unspecified). Ablation was attempted in 241 procedures, with acute success in 87% (AS 89%, MS 83%). Recurrence was evident in 18% of successful ablation procedures (AS 18%, MS 19%). Success rates were higher with repeat procedures than with primary procedures (P = .006). Multiple approaches were more often used for AS pathways, though no single approach was superior. There was no difference in success when comparing energy modalities, though the overall recurrence rate was higher for cryoablation. Significant complications occurred in 1.2% of procedures, though no patient had complete heart block. CONCLUSION: Ablation of AS and MS pathways remains challenging. Multiple approaches are often necessary to successfully ablate AS pathways. While both ablation energy modalities were equally successful, cryoablation may be associated with a higher chance of recurrence. Recurrences and repeat procedures may be anticipated to minimize risk to normal atrioventricular conduction during ablation in these regions.

Sudden unexpected death in asymptomatic infants due to PPA2 variants.

BACKGROUND: Sudden death in children is a tragic event that often remains unexplained after comprehensive investigation. We report two asymptomatic siblings who died unexpectedly at approximately 1 year of age found to have biallelic (compound heterozygous) variants in PPA2. METHODS: The index case, parents, and sister were enrolled in the Sudden Unexplained Death in Childhood Registry and Research Collaborative, which included next-generation genetic screening. Prior published cases of PPA2 variants, along with the known biology of PPA2, were also summarized. RESULTS: Whole exome sequencing in both siblings revealed biallelic rare missense variants in PPA2: c.182C > T (p.Ser61Phe) and c.380G > T (p.Arg127Leu). PPA2 encodes a mitochondrially located inorganic pyrophosphatase implicated in progressive and lethal cardiomyopathies. As a regulator and supplier of inorganic phosphate, PPA2 is central to phosphate metabolism. Biological roles include the following: mtDNA maintenance; oxidative phosphorylation and generation of ATP; reactive oxygen species homeostasis; mitochondrial membrane potential regulation; and possibly, retrograde signaling between mitochondria and nucleus. CONCLUSIONS: Two healthy and asymptomatic sisters died unexpectedly at ages 12 and 10 months, and were diagnosed by molecular autopsy to carry biallelic variants in PPA2. Our cases add additional details to those reported thus far, and broaden the spectrum of clinical and molecular features of PPA2 variants.

A homozygous SCN5A mutation associated with atrial standstill and sudden death.

BACKGROUND: Atrial standstill is an arrhythmogenic condition characterized by the absence of spontaneous electrical and mechanical atrial activity or in response to stimulation. There are few reported familial cases which have been associated with SCN5A mutations cosegregating with GJA5 or RYR2; however, isolated SCN5A mutations are rare. OBJECTIVE: The purpose of this study was to determine the clinical and biophysical consequence of a novel SCN5A mutation identified in a family with progressive atrial standstill and sudden death. METHODS: The family of a sporadic case of congenital atrial standstill underwent genetic screening. Human Embryonic Kidney 293 cells were transfected with wild-type (WT) or mutant SCN5A cDNAs. Biophysical properties were studied using whole-cell using patch clamp methods. RESULTS: A novel homozygous SCN5A mutation, p.V1340L, was identified in the proband and her sister. The proband had complete atrial standstill whereas the sister had partial atrial standstill. Heterozygous mutations were identified in the mother, father, and brother. All three had normal sinus rhythm and were asymptomatic. The mutant Nav1.5(V1340L) reduced Nav1.5 current density as well as showed a depolarizing shift in the voltage-dependent steady-state activation (WT: -35.3 ± 1.62 mV; V1340L: -22.4 ± 2.59 mV; P  =  0.001). CONCLUSIONS: A homozygous loss-of-function SCN5A mutation likely results in atrial standstill and sudden death due to suppression of initiation of action potential.

Epicardial ablation of tachyarrhythmia in children: Experience at two academic centers.

BACKGROUND: Experience with percutaneous epicardial ablation of tachyarrhythmia in pediatrics is limited. This case series addresses the feasibility, safety, and complications of the procedure in children. METHODS: A total of nine patients underwent 10 epicardial ablation procedures from 2002 to 2013 at two academic centers. Activation mapping was performed in all cases, and electroanatomic map was utilized in nine of the 10 procedures. Patients had undergone one to three failed endocardial catheter ablations in addition to medical management, and all had symptoms, a high-risk accessory pathway (AP), aborted cardiac arrest with Wolff-Parkinson-White syndrome (WPW), or ventricular dysfunction. A standard epicardial approach was used for access in all cases, using a 7- or 8- Fr sheath. Epicardial ablation modality was radiofrequency (RF) in seven, cryoablation (CRYO) in one, and CRYO plus RF in one. RESULTS: Median age was 14 (range 8-19) years. INDICATIONS: drug refractory ectopic atrial tachycardia (one), ventricular tachycardia (VT) (five), high-risk AP (two), and aborted cardiac arrest from WPW - (one). Epicardial ablation was not performed in one case despite access due to an inability to maneuver the catheter around a former pericardial scar. VT foci included the right ventricular outflow tract septum, high posterior left ventricle (LV), LV outflow tract, postero-basal LV, and scar from previous rhabdomyoma surgery. WPW foci were in the area of the posterior septum and coronary sinus in all three cases. Overall procedural success was 70% (7/10), with epicardial ablation success in five and endocardial ablation success after epicardial mapping in two. The VT focus was close to the left anterior descending coronary artery in one of the unsuccessful cases in which both RF and CRYO were used. There was one recurrence after a successful epicardial VT ablation, which was managed with a second successful epicardial procedure. There were no other recurrences at more than 1 year of follow-up. Complications were minimal, with one case of inadvertent pleural access requiring no specific therapy. No pericarditis or effusion was seen in any of the patients who underwent epicardial ablation. CONCLUSION: Epicardial ablation in pediatric patients can be performed with low complications and acceptable success. It can be considered for a spectrum of tachycardia mechanisms after failed endocardial ablation attempts and suspected epicardial foci. Success and recurrence may be related to foci in proximity to the epicardial coronaries, pericardial scar, or a distant location from the closest epicardial location. Repeat procedures may be necessary.