Faculty Bibliography

[This corrects the article DOI: 10.1016/j.eclinm.2024.102809.].

Hyperlactatemia is a common and concerning finding in the paediatric cardiac ICU as it may signify tissue hypoperfusion and/or hypoxia. However, it is important to include other aetiologies for an elevated lactate in the differential, especially when the lactate is significantly elevated (> 8 mmol/L). We present the case of metabolic acidosis with severe hyperlactatemia secondary to Warburg effect and presumed thiamine deficiency in a paediatric heart transplant patient with post-transplant lymphoproliferative disorder.

BACKGROUND:Parents of pediatric heart transplant (HTx) recipients have a unique perspective on the challenges associated with the transition into adult care networks. We sought to assess parental perceptions of the challenges pediatric HTx recipients face daily and parental concerns around the transition from pediatric care networks. METHODS:A 15-item online survey was developed in partnership with parent-stakeholders and administered to parents of pediatric HTx recipients in September 2023. Closed and open-ended questions assessed (1) the patients' diagnosis, age at diagnosis, and age at transplant, (2) parents' daily concerns about their child's well-being, (3) parents' overall concerns about their child's well-being as they transition into adulthood, (4) parents' perceptions of their child's quality-of-life (QoL) and health, and (5) parents' demographic characteristics. RESULTS:Eighty-six parents completed the survey. On a scale of 1 (worst) to 10 (best), 75% of parents rated their child's overall QoL at 8 or higher and 76% rated their child's health-related QoL at 8 or higher. Parents' daily concerns about their child's well-being included infectious diseases, health behaviors and care management, transplant-related concerns, socialization and education, mental health, and care coordination. Concerns related to the transition into adulthood included health behaviors and self-management, life satisfaction, finances, family, transplant-related concerns, and care coordination. CONCLUSIONS:Although parents of pediatric HTx recipients reported mostly positive QoL outcomes, they have concerns related to care management, life satisfaction, and healthcare access as their children transition into adulthood. Comprehensive transition-specific interventions and guidelines are needed to support families during this high-risk period.

BACKGROUND:Although sustained monomorphic ventricular tachycardia (MVT) in repaired tetralogy of Fallot (TOF) is linked to abnormally conducting anatomical isthmuses, the clinical importance of inducible polymorphic ventricular tachycardia (PVT) is unclear. OBJECTIVES/OBJECTIVE:The aim of this study was to determine the clinical and electrophysiological characteristics of inducible PVT in TOF. METHODS:Patients from the ongoing CATAPULT-TOF (Catheter Ablation of Ventricular Tachycardia Before Transcatheter Pulmonary Valve Replacement in Repaired Tetralogy of Fallot) registry with inducible sustained PVT at index electrophysiology study were included. Abnormal anatomical isthmus was defined as conduction velocity <0.5 m/s. Centrally adjudicated episodes with ≥3 consecutive beats of similar morphology (10 of 12 leads) were labeled transiently organized PVT (TO-PVT). TO-PVT was analyzed in relation to three-dimensional substrate characteristics and postablation inducibility. RESULTS: = 0.001). CONCLUSIONS:Patients with inducible PVT display a lower clinical risk profile and healthier myocardial substrate than those with MVT. Organized beats at episode onset appear to be associated with anatomical isthmuses that can be targeted by catheter ablation.

BACKGROUND:Paediatric pharmacokinetic and safety data for clofazimine are limited. We described the pharmacokinetics and safety of clofazimine in South African children treated for multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB). METHODS:Children <18 years being routinely treated for MDR/RR-TB were eligible for study participation. Soft gel capsules (Novartis Pharma AG) were administered using WHO-recommended weight-based dosing. Sparse and semi-intensive pharmacokinetic sampling was completed at baseline, Week 2 and 16. Clofazimine weekly area-under-the-concentration-time-curve (wAUC) was compared to target wAUC (60.87 mg*h/L and 111.79 mg*h/L) in adults receiving clofazimine 100mg daily for MDR/RR-TB and leprosy, respectively. Safety monitoring included measurement of QT-interval prolongation and laboratory assessment. RESULTS:Twenty children, six (30%) male, median age 6.0 years (range, 1.6-14.4), were included. Median clofazimine wAUC was 162.94 (IQR 130.06-263.95), >25% higher than the target adult wAUC in adults with MDR/RR-TB (111.79; IQR 81.9-151.9). No serious or grade ≥3 cardiac events occurred. There was a linear relationship between clofazimine concentration and QT-interval prolongation with an increase of 0.02 ms for every µg/L. There were 59 adverse events at least possibly related to clofazimine; one severe adverse event (elevated ALT) led to temporary withdrawal of clofazimine. CONCLUSIONS:Clofazimine doses used achieved substantially higher exposures in children than adults receiving standard clofazimine doses. The association of higher clofazimine exposures and QT-interval prolongation may pose unnecessary risk to children, particularly in combination with other QT-prolonging drugs. Lower clofazimine doses to achieve appropriate clofazimine exposures should be investigated in children using different drug formulations and harmonised weight bands.

PURPOSE/OBJECTIVE:In October 2018, the OPTN changed adult heart transplant (HT) allocation policy, increasing the number of adult candidates that had higher priority than pediatric candidates, potentially disadvantaging pediatric waitlist registrants. METHODS:To understand the impact of this policy change, we used SRTR data to identify 1469 pre-policy (7/2016-9/2018) and 2901 (10/2018-12/2022) post-policy pediatric (< 18 years) HT registrants. We quantified mortality and transplant risks using weighted cause-specific hazard models, and then using weighted competing risks regression. We further stratified these analyses by age to understand risks for those in direct competition with adults for organs (≥ 12 years). RESULTS:, p = 0.02). Post policy, 1-year transplant rate did not change in those < 12years (68.2%-71.0%, p = 0.77), but in those ≥ 12years, transplant rate increased (77.3%-81.0%, p = 0.003). CONCLUSIONS:Mortality on the waitlist decreased and access to HT for pediatric registrants did not decline following the 2018 policy change. The decreased mortality rate may reflect changes in patient casemix and/or improved patient care. Continued surveillance is important in ensuring equity in pediatric, and adult, HT.

BACKGROUND:The optimal pacemaker programming strategy for infants with isolated congenital complete atrioventricular block (CCAVB) remains unresolved. Dual-chamber pacing maintains atrioventricular synchrony and physiological heart rate variability but increases the burden of ventricular pacing on a myocardium that may be inherently prone to left ventricular (LV) dysfunction. OBJECTIVES/OBJECTIVE:This study sought to compare clinical outcomes of dual (DDD)- vs single (VVI)- chamber pacing in infants with CCAVB (DAVINCHI). METHODS:A multicenter retrospective study (2006-2023) identified infants with CCAVB and pacemaker implant at <1 year, with single-site ventricular pacing and no significant congenital heart disease. Outcome measured were clinically significant LV dysfunction, mortality, and complications. RESULTS:A total of 109 infants (64% autoimmune CCAVB) were identified, 60.6% had VVI pacing. Over a median follow-up of 5 years, 60 complications occurred in 47 subjects (43.1%). Smaller infants had more complications. Clinically significant LV dysfunction developed in 11 (10.1%) and was more frequent in DDD (21% vs 3%; P = 0.006). LV dysfunction resulted in mortality in 1 patient and 10 patients required a change in pacing mode. Independent risk factors for LV dysfunction were DDD pacing and neonatal implant. Right ventricular pacing lead placement had a higher HR (HR: 2.67) for LV dysfunction but was not statistically significant (P = 0.2). CONCLUSION/CONCLUSIONS:DDD pacing increases LV dysfunction risk compared with VVI in infants with CCAVB. Single-chamber LV apical pacing should be considered in infants with isolated CCAVB who require pacing. There is a high risk of pacing-related complications, particularly with an increased risk of ventricular lead complications in low-weight neonates.

BACKGROUND:Ventricular tachycardia (VT) substrate characteristics before transcatheter pulmonary valve replacement (TPVR) in repaired tetralogy of Fallot (rTOF) are unknown. OBJECTIVES/OBJECTIVE:In this study, the authors sought to evaluate substrates for sustained monomorphic VT before TPVR in rTOF. METHODS:Retrospective (2017 to 2021) and prospective (commencing 2021) rTOF patients with native right ventricular outflow tract referred for electrophysiology study (EPS) before TPVR were included. Electrophysiologic findings and outcomes of VT ablation were determined. RESULTS:One-hundred eighty patients (mean age 39 ± 14 years, 54% male, 71 retrospective, 109 prospective) were identified. At EPS, monomorphic VT was induced in 45 (25%), and a slowly conducting anatomic isthmus alone was observed in 40 (22%). VT isthmus conduction velocity decreased (-0.08 m/s per decade; P = 0.008) and VT inducibility (P < 0.001 for trend) and cycle length (CL) (+15 ms per decade, P = 0.005) increased with age. Multivariable factors associated with shorter VT CL included preserved isthmus conduction velocity (-50 ms per m/s; P = 0.02), absence of atrial flutter (-18 ms; P = 0.007), and improved RV ejection fraction (-16 ms per 10% increase; P = 0.007). Catheter ablation was acutely successful in 80/83 (96%). At repeated EPS after a median of 5 months, previously ablated substrates were evident in 3/24 (13%) and new VT substrates in 3/33 (9%). CONCLUSIONS:Pre-TPVR VT substrates in rTOF demonstrate age-related degeneration that was associated with VT inducibility and VT CL. Both recovery of VT isthmus conduction and new VT substrates were observed after TPVR despite successful catheter ablation.

BACKGROUND:Pretransplant functional, motor, cognitive, and academic deficits are common in pediatric patients requiring heart transplantation (HT); some persist post-HT. We assessed the association between these quality of life (QoL) deficits and post-HT outcomes. METHODS:Using SRTR data 2008-2023, we evaluated the functional, motor, cognitive, and academic status of pediatric HT recipients from listing to 15 years post-HT. We compared all-cause graft survival among patients with vs. without pre-HT deficits using Cox regressions. Among patients with a functioning graft at 1 year, we assessed the association between deficits at that time and subsequent graft failure. RESULTS:, p < 0.001). CONCLUSION/CONCLUSIONS:Pediatric HT recipients with decreased functional status are at higher risk for graft failure and mortality. These patients may benefit from early intervention aimed at improving functional status.

Progressive cardiac conduction defect often associated with variants in sodium voltage-gated channel SCN5A gene and variants in the L-type calcium voltage-gated channel CACNA1D gene are implicated in sinoatrial node dysfunction. We generated an induced pluripotent stem cell line (iPSC) from a 13-year-old patient with history of conduction system disease and ventricular tachycardia, carrying variants in SCN5A (c.2618C > G), CACNA1D (c.3786G > T), and DSP (c.1582C > G). The generated iPSC line exhibited pluripotency markers, differentiated into the three embryonic germ layers, and maintained a normal karyotype. This iPSC line offers insights into the pathophysiological mechanisms of cardiac arrhythmias and personalized therapies development.