Conduction System Pacing in Pediatrics and Congenital Heart Disease: A Case Report and Literature Review.

Conduction system pacing involving either His bundle pacing (HBP) or left bundle branch pacing (LBBP) is a modality that has been introduced as a safe and effective alternative to right ventricular (RV) pacing to help prevent pacemaker-associated cardiomyopathy. While HBP has been employed in the pediatric and congenital populations, several small studies have shown LBBP to be safe and effective in the pediatric population. We present a patient with congenital atrioventricular block and postoperative ventricular septal defect repair cardiomyopathy with subsequent left ventricular function improvement following a transition from an RV epicardial pacemaker system to an LBBP system. This case report serves as a foundation for a review of the current state of LBBP in pediatrics and congenital heart disease.

Novel NKX2.5 variant associated with congenital heart disease and increased risk of malignant arrhythmia and sudden cardiac death.

INTRODUCTION: The NKX2.5 gene is an important cardiac developmental transcription factor, and variants in this gene are most commonly associated with CHD. However, there is an increased need to recognise associations with conduction disease and potentially dangerous ventricular arrhythmias. There is an increased risk of arrhythmia and sudden cardiac death in patients with NKX2.5 variants, an association with relatively less attention in the literature. METHODS: We created a family pedigree and reconstructed familial relationships involving numerous relatives with CHD, conduction disease, and ventricular non-compaction following the sudden death of one family member. Two informative but distantly related family members had genetic testing to determine the cause of arrhythmias via arrhythmia/cardiomyopathy gene testing, and we identified obligate genetic-positive relatives based on family relationships and Mendelian inheritance pattern. RESULTS: We identified a novel pathogenic variant in the NKX2.5 gene (c.437C > A; p. Ser146*), and segregation analysis allowed us to link family cardiac phenotypes including CHD, conduction disease, left ventricular non-compaction, and ventricular arrhythmias/sudden cardiac death. CONCLUSIONS: We report a novel NKX2.5 gene variant linking a spectrum of familial heart disease, and we also encourage recognition of the association between NKX2.5 gene and potentially dangerous ventricular arrhythmias, which will inform clinical risk stratification, screening, and management.

The Effects of Cardiac Implantable Electronic Device Personal Protective Equipment Use in Patients with Pediatric and Adult Congenital Heart Disease.

Pediatric and adult congenital heart disease (ACHD) patients encounter physical and emotional barriers. Cardiac implantable electronic devices (CIEDs), including pacemakers and implantable cardiac defibrillators (ICD) often compound these issues. Patient fear associated with damaging the CIED system can lead to avoidance of physical activity and reduced quality of life (QOL). CIED personal protective equipment (PPE) is a potential treatment for decreasing this fear. We sought to determine the effects of CIED PPE use in the pediatric and ACHD population. Patients 5 years or older with a CIED at a single pediatric and ACHD heart rhythm center received a CIED protector and customized athletic shirt. QOL was assessed using the PedsQL TM 4.0 SF15 prior to and after 6-12 months. Of the 77 patients enrolled, 26 completed repeat assessment. The mean age at enrollment was 15.6 years (range 5-36) with a mean device age of 2.2 years (< 1-10 years). Pacemakers were present in 77% and 23% had ICDs. The PPE was used in 92% with no PPE malfunction. Fear associated with physical activity was reduced, z = - 4, p < 0.001, with a large effect size (r = 0.55). There was a trend toward increased physical activity. Total QOL scores improved, z = - 2.771, P < 0.05, with a medium effect size (r = 0.4). This first study of CIED PPE in children shows that providing CIED PPE to pediatric and ACHD patients may decrease their fear of damaging their device system, increasing physical activity levels, and improving quality of life.

Tolerability and Safety of Lacosamide in Neonatal Population.

Lacosamide is a newer antiepileptic medication used in refractory neonatal seizures with limited safety and efficacy data. This case series spans 4 years and includes 38 neonates cared for in the neonatal, pediatric, and cardiovascular intensive care units, who received lacosamide for refractory seizures. Because lacosamide affects atrioventricular node function in adults, among other metrics, electrocardiogram (ECG) changes were monitored closely in these neonates. Within this cohort, 2 neonates were found to have atrial bigeminy on ECG and telemetry. Otherwise, lacosamide was generally well tolerated with sleepiness being the most common symptom noted. This case series reports data on the tolerability of lacosamide and emphasizes the importance of monitoring key cardiac intervals with ECG before and after the use of lacosamide in this population.

Quality of life of children and young adults with and without cardiovascular implantable electronic devices during the COVID-19 pandemic.

BACKGROUND: Children with cardiovascular implantable electronic devices (CIEDs) have a lower quality of life (QoL) compared to the general pediatric population. The combined effect of COVID-19 and CIEDs on the QoL and physical activity (PA) both within and between each population is unknown. METHODS: Individuals 8-25-year-old with and without CIED's were recruited to complete a phone survey. Data collection included demographics, the Pediatric Quality of Life Inventory (PedsQL), and the (PAQ). PedsQL and PAQ scores range from 0-100 and 1-5, respectively, with higher scores indicating a higher QoL and PA. RESULTS: Of the 190 individuals contacted, 148 participated (CIED n = 76, non-CIED n = 72), for an 81% response rate. Participants with and without CIEDs were similar in age (15.5 vs. 16 years, p = .57), gender (male = 57% vs. 42%, p = .07), and self-identified race (white = 79% vs. 81%, p = .44). CIED participants had a lower QoL (70.8 vs. 83.3, p < .001). Lower total scores were noted in CIED participants with structural heart disease compared to those without (71.6 vs. 83.6, p = .035) and those with a history of non-CIED heart or chest surgery compared to those without (71.3 vs. 83.3, p = .035). PAQ scores were similarly lower for CIED participants (2.17 vs. 2.73, p < .001). CONCLUSION: The presence of a CIED negatively impacts the QoL and PA of the pediatric population in the setting of the COVID-19 pandemic. Further research is needed to better understand and address the drivers of decreased QoL and PA in the pediatric CIED population in the setting of the COVID-19 Pandemic.

Cardiovascular Health of Youth During Gender-Affirming Testosterone Treatment: A Review.

PURPOSE: Many birth-assigned female/transgender male and nonbinary people (identified as masculine spectrum here) begin gender-affirming testosterone therapy by the age of 24 years. Few data inform assessment of cardiovascular health of masculine spectrum youth as a specific subgroup of the 1.5 million transgender people in the United States. The purpose of this review is to help youth-serving practitioners consider, understand, and evaluate cardiovascular health in adolescent and young adult masculine spectrum patients receiving gender-affirming testosterone treatment. METHODS: This is a narrative review intended to synthesize a broad body of clinical and research literature. RESULTS: Common cardiovascular health changes associated with testosterone include increased red blood cell mass and likely insignificant changes in high-density lipoprotein and low-density lipoprotein levels. Changes in heart mass, heart electrophysiology, and endothelial reactivity are likely, based on extrapolation of data from adults. Testosterone may have indirect effects on cardiovascular health through influences on depression, anxiety, stress, and anorexia nervosa as well as on behaviors such as tobacco use. CONCLUSIONS: Testosterone contributes importantly to the cardiovascular health and well-being of masculine spectrum gender-diverse youth. We need to do a better job of supporting these young people with data on cardiovascular health over the life span.

Evaluation of age at symptom onset, proband status, and sex as predictors of disease severity in pediatric catecholaminergic polymorphic ventricular tachycardia.

BACKGROUND: Children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for sudden death, and a risk stratification tool does not exist. OBJECTIVE: The purpose of this study was to determine whether proband status, age at symptom onset, and/or sex are independent predictors of cardiac events. METHODS: A multicenter, ambispective, cohort of pediatric CPVT patients was categorized by sex, proband status, and age at symptom onset (D1: first decade of life [symptom onset <10 years] or D2: second decade of life [symptom onset 10-18 years, inclusive]). Demographics, therapy, genetics, and outcomes were compared between groups. RESULTS: A total of 133 patients were included and stratified into 58 D1 and 75 D2 patients (68 female and 65 male; 106 probands and 27 relatives). Localization of RYR2 variants to hotspots differed based on proband status and age at symptom onset. The cardiac event rate was 33% (n = 44/133), inclusive of a 3% (n = 4/133) mortality rate, over a median of 6 years (interquartile range 3-11) after time of symptom onset. Proband status, rather than age at of symptom onset or sex, was an independent predictor of time to first cardiac event (P = .008; hazard ratio = 4.4). The 5-, 10- and 15-year event-free survival rates for probands were 77%, 56%, and 46%, respectively, and for relatives were 96%, 91%, and 86%, respectively. Event risk after diagnosis was 48% (32/67) in patients on ß-blocker or flecainide alone vs 10% (5/48) in patients on ß-blocker plus flecainide and/or left cardiac sympathetic denervation (P <.001). CONCLUSION: Proband status, but not age at symptom onset or male sex, independently predicted an earlier onset of cardiac events. A larger sample size would enable a comprehensive investigation of other risk factors.

Permanent His Bundle Pacing in Patients With Congenital Complete Heart Block: A Multicenter Experience.

OBJECTIVES: This study retrospectively assessed the safety and efficacy of permanent His bundle pacing (HBP) in patients with congenital complete heart block (CCHB). BACKGROUND: HBP has become an accepted form of pacing in adults. Its role in CCHB is not known. METHODS: Seventeen patients with CCHB who underwent successful HBP were analyzed at 6 academic centers between 2016 and 2019. Nine patients had de novo implants, and 8 patients had previous right ventricular (RV) leads. Three RV paced patients had reduced left ventricular ejection fractions at the time of HBP. Implant/follow-up device parameters, New York Heart Association functional class, QRS duration, and left ventricular ejection fraction data were analyzed. RESULTS: Patients' mean age was 27.4 ± 11.3 years, 59% were women, and mean follow-up was 385 ± 279 days. The following parameters were found to be statistically significant between implant and follow-up, respectively: impedance, 602 ± 173 Ω versus 460 ± 80 Ω (p < 0.001); and New York Heart Association functional class, 1.7 ± 0.9 versus 1.1 ± 0.3 (p = 0.014). In patients with previous RV pacing, HBP resulted in a significant decrease in QRS duration: 167.1 ± 14.3 ms versus 118.3 ± 13.9 ms (p < 0.0001). In de novo implants, HBP resulted in increases in QRS duration compared with baseline: 111.1 ± 19.4 ms versus 91.0 ± 4.8 ms (p = 0.016). Other parameters exhibited no statistically significant differences. During follow-up, 2 patients required lead revision due to elevated pacing thresholds. CONCLUSIONS: HBP seems to be safe and effective, with improvement in clinical outcomes in patients with CCHB. Larger studies with longer follow-up periods are required to confirm our findings.

Subcutaneous Implantable Cardioverter-Defibrillators in Pediatrics and Congenital Heart Disease: A Pediatric and Congenital Electrophysiology Society Multicenter Review.

OBJECTIVES: The primary goal of this study was to evaluate the implant experience and midterm results of subcutaneous implantable cardioverter-defibrillators (S-ICDs) in pediatric patients and those with congenital heart disease. BACKGROUND: The S-ICD was developed to avoid the lead-related complications associated with transvenous systems. The absence of intravascular or intracardiac components offers potential advantages to pediatric patients and those with congenital heart disease. METHODS: This international, multicenter, retrospective, standard-of-care study was conducted through the Pediatric & Congenital Electrophysiology Society. Complications at 30 and 360 days, inappropriate shocks, and delivery of appropriate therapy were assessed. RESULTS: The study included 115 patients with a median follow-up of 32 (19 to 52) months. Median age was 16.7 years (14.8 to 19.3 years), 29% were female, and 55% had a primary prevention indication. Underlying disease substrate was cardiomyopathy (40%), structural heart disease (32%), idiopathic ventricular fibrillation (16%), and channelopathy (13%). The complication rate was 7.8% at 30 days and 14.7% at 360 days. Overall, inappropriate shocks occurred in 15.6% of patients, with no single clinical characteristic reaching statistical significance. At implant, 97.9% of patients had successful first shock conversion with 96% requiring ≤65 J. Appropriate therapy was delivered to 11.2% of patients with an annual incidence of 3.9% and an acute first shock conversion success rate of 92.5%. CONCLUSIONS: This study found that in a heterogeneous population of pediatric patients and those with congenital heart disease, the S-ICD had comparable rates of complications, inappropriate shocks, and conversion efficacy compared with previously published studies on transvenous systems in similar populations.

Permanent His-bundle Pacing in Pediatrics and Congenital Heart Disease.

Permanent His-bundle pacing has been gaining popularity in the adult population requiring cardiac resynchronization therapy. Initial procedural challenges are being overcome, and this method of pacing has been shown to improve left ventricular function and heart failure symptoms secondary to ventricular dyssynchrony. Though the etiologies of ventricular dyssynchrony may differ in children and those with congenital heart disease than in adults with structurally normal hearts, His-bundle pacing may also be a preferred option in these groups to restore more physiologic electric conduction and improve ventricular function. We present a review of the current literature and suggested directions involving deploying permanent His-bundle pacing in the pediatric and congenital heart disease population.

Permanent conduction system pacing for congenitally corrected transposition of the great arteries: A Pediatric and Congenital Electrophysiology Society (PACES)/International Society for Adult Congenital Heart Disease (ISACHD) Collaborative Study.

BACKGROUND: Congenitally corrected transposition of the great arteries (CCTGA) is associated with spontaneous atrioventricular block and pacing-induced cardiomyopathy. Conduction system pacing is a potential alternative to conventional cardiac resynchronization therapy (CRT). OBJECTIVE: The purpose of this study was to determine the outcomes of conduction system pacing for CCTGA. METHODS: Retrospective data were collected from 10 international centers. RESULTS: His bundle (HBP) or left bundle branch pacing (LBBP) was attempted in 15 CCTGA patients (median age 23 years; 87% male). Previous surgery had been performed in 8 and chronic ventricular pacing in 7. Conduction system pacing (11 HBP, 2 LBBP 2; nonselective in 10, selective in 3) was acutely successful in 13 (86%) without complication. In 9 cases, electroanatomic mapping was available and identified the distal His bundle and proximal left bundle branches within the morphologic left ventricle below the pulmonary valve separate from the mitral annulus. Median implant HV interval was 42 ms (interquartile range [IQR] 35-48), R wave 6 mV (IQR 5-18), and threshold 0.5 V (IQR 0.5-1.2) at median 0.5 ms. QRSd was unchanged compared to junctional escape rhythm (124 vs 110 ms; P = .17) and decreased significantly compared to baseline ventricular pacing (112 vs 164 ms; P <.01). At a median of 8 months, all patients were alive without significant change in pacing threshold or lead dysfunction. New York Heart Association functional class improved in 5 patients. CONCLUSION: Permanent conduction system pacing is feasible in CCTGA by either HBP or proximal LBBP. Narrow paced QRS and stable lead thresholds were observed at intermediate follow-up. Unique anatomic characteristics may favor this approach over conventional CRT.

Clinical characterisation of a novel SCN5A variant associated with progressive malignant arrhythmia and dilated cardiomyopathy.

INTRODUCTION: The SCN5A gene is implicated in many arrhythmogenic and cardiomyopathic processes. We identified a novel SCN5A variant in a family with significant segregation in individuals affected with progressive sinus and atrioventricular nodal disease, atrial arrhythmia, dilated cardiomyopathy, and early sudden cardiac arrest. METHODS: A patient pedigree was created following the clinical evaluation of three affected individuals, two monozygotic twins and a paternal half-brother, which lead to the evaluation of a paternal half-sister (four siblings with the same father and three mothers) all of whom experienced varying degrees of atrial arrhythmias, conduction disease, and dilated cardiomyopathy in addition to a paternal history of unexplained death in his 50s with similar autopsy findings. The index male underwent sequencing of 58 genes associated with cardiomyopathies. Sanger sequencing was used to provide data for bases with insufficient coverage and for bases in some known regions of genomic segmental duplications. All clinically significant and novel variants were confirmed by independent Sanger sequencing. RESULTS: All relatives tested were shown to have the same SCN5A variant of unknown significance (p. Asp197His) and the monozygotic twins shared a co-occurring NEXN (p. Glu575*). Segregation analysis demonstrates likely pathogenic trait for the SCN5A variant with an additional possible role for the NEXN variant in combination. CONCLUSIONS: There is compelling clinical evidence suggesting that the SCN5A variant p. Asp197His may be re-classified as likely pathogenic based on the segregation analysis of our family of interest. Molecular mechanism studies are pending.

Early conversion of classic Fontan conversion may decrease term morbidity: single centre outcomes.

BACKGROUND: The initial classic Fontan utilising a direct right atrial appendage to pulmonary artery anastomosis led to numerous complications. Adults with such complications may benefit from conversion to a total cavo-pulmonary connection, the current standard palliation for children with univentricular hearts. METHODS: A single institution, retrospective chart review was conducted for all Fontan conversion procedures performed from July, 1999 through January, 2017. Variables analysed included age, sex, reason for Fontan conversion, age at Fontan conversion, and early mortality or heart transplant within 1 year after Fontan conversion. RESULTS: A total of 41 Fontan conversion patients were identified. Average age at Fontan conversion was 24.5 ± 9.2 years. Dominant left ventricular physiology was present in 37/41 (90.2%) patients. Right-sided heart failure occurred in 39/41 (95.1%) patients and right atrial dilation was present in 33/41 (80.5%) patients. The most common causes for Fontan conversion included atrial arrhythmia in 37/41 (90.2%), NYHA class II HF or greater in 31/41 (75.6%), ventricular dysfunction in 23/41 (56.1%), and cirrhosis or fibrosis in 7/41 (17.1%) patients. Median post-surgical follow-up was 6.2 ± 4.9 years. Survival rates at 30 days, 1 year, and greater than 1-year post-Fontan conversion were 95.1, 92.7, and 87.8%, respectively. Two patients underwent heart transplant: the first within 1 year of Fontan conversion for heart failure and the second at 5.3 years for liver failure. CONCLUSIONS: Fontan conversion should be considered early when atrial arrhythmias become common rather than waiting for severe heart failure to ensue, and Fontan conversion can be accomplished with an acceptable risk profile.

All Along the Watchtower: a Case of Long QT Syndrome Misdiagnosis Secondary to Genetic Testing Misinterpretation.

Clinical genetics services continue to expand into diverse medical specialties. An ever-increasing number of non-genetics providers are independently ordering genetic tests, interpreting results, and at times, making diagnoses leading to patient care recommendations. Non-genetics healthcare providers can help increase patient access to these services, but a potential pitfall occurs when these providers either do not have adequate expertise with genetic variant interpretation or do not have access to multi-disciplinary teams including genetic counselors or clinical geneticists for advanced review. In the cardiology setting, variant misinterpretation can lead to misattribution of disease risk, unnecessary treatments or management, and potentially adverse psychosocial and financial effects. To address this, case reports and series are needed to highlight variant misinterpretation and misdiagnoses, including discussion of possible solutions and best practices for avoidance. This report details a child previously diagnosed with long QT syndrome type 4 by chromosomal microarray who was then subsequently managed for this disease by cardiac providers with insufficient expertise to critically review and question the genetic testing results. The patient was eventually referred to a pediatric electrophysiology team as part of a larger multidisciplinary cardiovascular genetics program, composed of specialist genetic counselors, cardiologists, and clinical geneticists. Advanced review and clinical evaluation raised concern about the initial genetic testing result and diagnosis. Complementary testing with a different modality to confirm or disconfirm the chromosome microarray result was performed, providing evidence that the original result reflected analytic error in the laboratory as well as interpretive error by the clinical geneticist and that the patient was misdiagnosed, and treated over the course of years, for long QT syndrome. This case shows the value of multidisciplinary teams caring for patients with inherited cardiovascular diseases.

Management of Complications Caused by a Massive Left Ventricle Tumor in a Neonate.

We report the case of a neonate born with a giant fibroma occupying the entirety of her left ventricle. Owing to the extensive resection, her postoperative course was complicated by severely diminished left ventricular function and complete heart block necessitating extracorporeal support. Ultimately, cardiac resynchronization therapy was used, after which the infant's ventricular function gradually improved and she was successfully discharged to home.

The Genetic Counselor in the Pediatric Arrhythmia Clinic: Review and Assessment of Services.

There are minimal data on the impact of genetic counselors in subspecialty clinics, including the pediatric arrhythmia clinic. This study aimed to describe the clinical encounters of a genetic counselor integrated into a pediatric arrhythmia clinic. In the 20 months between July 2015 and February 2017, a total of 1914 scheduled patients were screened for indications relevant for assessment by a genetic counselor. Of these, the genetic counselor completed 276 patient encounters, seeing 14.4% of all patients in clinic. The most expected and common indications for genetic counselor involvement were related to suspicion for primary heritable arrhythmia conditions, though patients seen in this clinic display a wide range of cardiac problems and many additional indications for genetic evaluation were identified. Roughly 75% (211/276) of encounters were for personal history of confirmed/suspected heritable disease, including cardiac channelopathies, cardiomyopathies, ventricular arrhythmias, and congenital heart defects, and 25% (65/276) were for family history of disease, including long QT syndrome and sudden unexplained death. Overall, this study shows that about 1 in 7 patients seen in a pediatric arrhythmia clinic have indications that likely benefit from genetic counselor involvement and care. Similar service delivery models embedding genetic counselors in pediatric arrhythmia clinics should be encouraged, and this model could be emulated to increase patient access to genetic counseling services.

Permanent nonselective His bundle pacing in an adult with L-transposition of the great arteries and complete AV block.

We report the placement of a permanent transvenous nonselective His bundle pacing lead in conjunction with a transvenous pacemaker/implantable cardioverter-defibrillator in an adult with Levo-Transposition of the Great Arteries (L-TGA) and a stenotic coronary sinus (CS) ostium, which would not accommodate a transvenous left ventricular (LV) pacing lead. Nonselective His bundle pacing provided a nearly identical ventricular activation pattern in this previously unpaced patient. Many L-TGA patients will have an eventual need for permanent pacing and, given the challenges of CS cannulation, His bundle pacing may represent a preferred modality rather than pure morphologic LV pacing or surgical systemic ventricular lead placement to achieve optimal electrical synchrony.

Significant Lead Migration of a Subcutaneous Implantable Cardioverter-Defibrillator in a Pediatric Patient.

Since its introduction, the subcutaneous implantable cardioverter-defibrillator (S-ICD) has provided the benefit of reduced mortality from ventricular tachyarrythmias without the associated short- and long-term morbidity of transvenous or epicardial implantable cardioverter-defibrillator (ICD) leads. As its name implies, the S-ICD system is implanted in its entirety, including device and lead, just under the skin beginning along the anterior axillary line, with its lead tunneled to the left parasternum and then from the xiphoid to the manubrium-sternal junction. Dislocation of the lead due to migration of the parasternal lead has been described in a minority of patients. Here, we describe an unusual case of a significant lead migration in a pediatric patient.