Faculty Bibliography

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.

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 consenus 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 follow-up 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, which is limited by the close proximity of normal atrioventricular (AV) conduction. OBJECTIVE: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 electrophysiologic (EP) studies performed between July, 2001 and July, 2017. Acute success and recurrence rates were assessed, comparing catheter approaches and energy utilized for ablation. RESULTS:255 EP 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 ablations (AS 18%, MS 19%). Success rates were higher with repeat procedures than primary procedures (P = 0.006). Multiple approaches were more often utilized for AS pathways, though no single approach was superior. There was no difference in success when comparing energy modalities, though overall recurrence was higher for cryoablation. Significant complications occurred in 1.2% of procedures, though no patient suffered from complete heart block. CONCLUSION/CONCLUSIONS: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 repeated procedures may be anticipated to minimize risk to normal AV conduction during ablation in these regions.

BACKGROUND: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:1.5 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:1.5-Q1475P trafficking defect, thus increasing mutant channel expression. CONCLUSIONS:1.5-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.

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.).

Adults with congenital heart disease (ACHD) are likely at increased risk for complications of COVID-19. ACHD centers should prepare to deliver routine cardiac care and support for patients with COVID-19 safely at home, as the number of COVID-19 infections worldwide continues to increase. This brief report aims to share the strategies we have used in our ACHD program to manage and treat our patients during this global health crisis at one of the initial epicenters of the pandemic in New York City, and offer suggestions for preparation for ACHD clinicians.

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.

Background: Implantable loop recorder (ILR) based monitoring of patients with LQTS allows enhanced arrhythmia surveillance and can help distinguish life-threatening from benign arrhythmias.
Objective(s): We present a case of a child with LQTS and wide complex tachycardia detected by ILR.
Result(s): An asymptomatic 12 year old with LQT2 syndrome, positive for a G648S hERG mutation, with baseline QTc of 510-550ms despite maximally tolerated Nadolol (Figure 1A) was followed in our inherited arrhythmia center. His affected mother has had multiple syncopal events related to polymorphic ventricular tachycardia (VT) and appropriate ICD shocks. We elected to implant him with ILR to allow longitudinal monitoring and early detection of arrhythmia. He presented 6 months later with 2 alerts for asymptomatic polymorphic, wide complex tachycardia at ~200 bpm during sleeping (Figure 1B). Electrophysiology study (EPS) was performed to determine etiology of the arrhythmia. Dual AV node physiology was present. Sinus tachycardia at 200 bpm with left bundle branch block (LBBB) morphology was induced with Isoproterenol and atrio-fascicular pathway was excluded. Respiratory changes resulted in the tachycardia appearing as polymorphic on the ILR during the EPS.
Conclusion(s): This is the first reported case of sinus tachycardia with LBBB aberrancy in a child with LQTS. Pseudopolymorphic wide complex tachycardia was the result of aberrancy and respiratory artifact. Combined ILR monitoring and EP study provided a correct diagnosis, thus avoiding further interventions. [Figure presented]
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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 co-segregating 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.