Assessment of paediatric exertional or peri-exertional syncope: does the story matter?

Exertional syncope has been suggested to correlate with a cardiac aetiology, particularly when occurring in mid-stride. The aim of the study is to evaluate the incidence of cardiac disease among children presenting with exertional syncope, determine the influence of timing within activity, and determine the utility of genetic testing and implantable event monitors in the evaluation of cardiac syncope. The patients ≤18 years old with exertional syncope who underwent exercise stress testing between 2008 and 2019 were retrospectively included. Patients were assessed to be in one of three groups: mid-exertion (mid-stride syncope), peri-exertion (syncope during activity but not moving), and post-exertion (within minutes of the activity). A total of 334 patients were included; 46 % were mid-exertion, 18 % were peri-exertion, and 36 % were post-exertion. Thirteen patients (3.8 %) were diagnosed with cardiac syncope; n = 9 (69 %) mid-exertion. Only mid-exertional syncope was significantly associated with a cardiac diagnosis (OR: 2.6). Cardiac diagnoses included inherited arrhythmia syndromes (n = 9), abnormal coronary origins (n = 2), and supraventricular tachycardia (n = 2). Only catecholaminergic polymorphic ventricular tachycardia (n = 5) was associated with mid-exertional syncope (OR: 1.4). The definitive diagnostic test was exercise testing (n = 8), echocardiogram (n = 2), genetic testing (n = 1), ambulatory monitor (n = 1), and EKG (n = 1). Mid-stride syncope was more likely to result in a cardiac diagnosis, and exercise testing is the most common definitive test as catecholaminergic polymorphic ventricular tachycardia was the primary aetiology of exertional syncope in our cohort. Implantable event monitors and genetic testing could be helpful in ruling out cardiac disease.

High-density electroanatomic mapping with grid catheter in pediatrics and congenital heart disease.

BACKGROUND: The Advisor™ HD Grid mapping catheter (Abbott Laboratories; Chicago, IL) allows for bipolar electrogram collection in both orthogonal and perpendicular planes, unique when compared to traditional and branch catheters. Experience in pediatric patients and congenital heart disease (CHD) is limited. The purpose of this work was to evaluate the utility and safety of the Advisor™ HD Grid mapping catheter in pediatric and CHD populations. METHODS: Retrospective review of all pediatric patients and those with CHD (regardless of age) at Children's Hospital Colorado and University of Colorado undergoing electrophysiologic study in which the Advisor™ HD Grid mapping catheter was utilized. RESULTS: Sixty-five procedures in 60 patients (N = 31 female (47.6%), median age 17 years (15-24.1)) were included. Patients had CHD in 30 procedures (46.1%). Eight-eight arrhythmia substrates were mapped including atrial flutter/intra-atrial reentrant tachycardia (N = 33), focal atrial tachycardia (N = 20), isolated PVCs (N = 10), accessory pathways (N = 9), atrioventricular nodal reentrant tachycardia (N = 7), right ventricular substrate mapping (N = 7), and ventricular tachycardia (N = 2). Median time per map was 11.8 (7.5-20.1) min with 3.2 (± 1.7) maps per procedure and a median of 2634 (1767-7654) points used per map. Patients with CHD required more maps (p < 0.001) and points per map (p < 0.001). Ablation was successful in 92.4% of procedures. CONCLUSIONS: The Advisor™ HD Grid mapping catheter is safe and effective in the pediatric and congenital heart disease population. A wide variety of arrhythmia substrates can be mapped with high point density and low mapping time.

Repolarization Dispersion Is Associated With Diastolic Electromechanical Discoordination in Children With Pulmonary Arterial Hypertension.

Background Electromechanical dyssynchrony is a well described comorbidity in pulmonary arterial hypertension (PAH). ECG-derived measurements reflective of diastolic dysfunction and electromechanical imaging markers are yet to be investigated. In this study we investigated the ECG- derived marker of repolarization dispersion, interval between the peak and end of T wave (TpTe), in pediatric patients with PAH and left ventricular (LV) diastolic dysfunction. Methods and Results We measured TpTe from a standard 12-lead ECG and in 30 children with PAH and matched control subjects. All participants underwent same-day echocardiography and myocardial strain analysis to calculate the diastolic electromechanical discoordination marker diastolic relaxation fraction. When compared with control subjects, patients with PAH had increased TpTe (93±15 versus 81±12 ms, P=0.001) and elevated diastolic relaxation fraction (0.33±0.10 versus 0.27±0.03, P=0.001). Patients with PAH with LV diastolic dysfunction had significantly increased TpTe when compared with patients with PAH without diastolic dysfunction (P=0.012) and when compared with control group (P<0.001). Similarly, patients with PAH with LV diastolic dysfunction had increased diastolic relaxation fraction when compared with PAH patients without diastolic dysfunction (P=0.007) and when compared with control group (P<0.001). A 10-ms increase in TpTe was significantly associated with 0.023 increase in diastolic relaxation fraction (P=0.008) adjusting for body surface area, heart rate, right ventricular volumes, and function. Conclusions Prolonged myocardial repolarization and abnormal LV diastolic electromechanical discoordination exist in parallel in children with PAH and are associated with worse LV diastolic function and functional class.

Transesophageal three-dimensional echocardiographic guidance for pacemaker lead extraction.

BACKGROUND: The ability of transesophageal three-dimensional echocardiography (3DE) to aid in pacemaker lead extraction has not yet been evaluated. 3DE provides real-time evaluation of intracardiac anatomy and the location of pacemaker leads in greater detail than either fluoroscopy or -two-dimensional echocardiography (2DE), aiding in the extraction of such leads, which can be potentially dangerous. We sought to investigate the feasibility and utility of 3DE to visualize intracardiac anatomy and pacemaker leads, and to assist in lead extraction procedures. METHODS: We utilized 3DE in nine encounters for eight different patients, to visualize intracardiac anatomy and leads before, during, and after extraction to evaluate the feasibility and utility to aid in the procedure and evaluate for potential sequelae. RESULTS: 3DE was able to identify pertinent intracardiac anatomy and leads in all cases. 3DE detected procedural complications or altered management in five of nine encounters (five of eight patients); this included detection of an avulsed papillary muscle, tricuspid valve leaflet damage, and cast/thrombus after lead removal, as well as adjustment of excess lead slack to avoid future valve damage, or risk stratification of lead removal. CONCLUSION: 3DE is feasible and adds utility to lead extraction cases by visualizing intracardiac anatomy and leads beyond fluoroscopy or 2DE, providing real-time information during extraction, and identifying potential complications.

Patients with bicuspid aortic valves may be associated with infra-hisian conduction disease requiring pacemakers.

BACKGROUND: Bicuspid aortic valves (BAVs) are associated with accelerated valvular dysfunction. Increasing rates of conduction system disease are seen in patients with calcific tricuspid aortic valves (TAVs). However, little is known regarding the extent of conduction disorders in BAV patients. We sought to determine the extent of infra-hisian conduction pathology among patients with BAVs undergoing EP studies. METHODS: We prospectively analyzed patients presenting to the EP laboratory from 2006 to 2017 at our institution. Thirty-three BAV patients had measured HV intervals. Each individual was matched by age and gender to two control patients. Clinical characteristics were collected and compared, and patients followed for outcomes. RESULTS: The BAV cohort had a mean age of 47.8 ± 17.2 years (range 19-76 years). Indications for referral to the EP lab in the BAV cohort included SVT ablation (n = 16), VT ablation (n = 10), and EP study for syncope, pre-syncope, or palpitations (n = 29). Patients with BAVs had a mean HV interval of 58.7 ms ± 18.6 ms, compared to a mean of 47.2 ms ± 9.6 ms for controls (p value = 0.0001). Over a 10-year follow-up period, 9 BAV patients (27%) went on to require permanent pacing compared to 6 patients (9%) in the control group (p value = 0.03). CONCLUSION: Compared to patients with TAVs presenting for EP evaluation, individuals with BAVs have longer HV intervals and a significantly increased requirement for pacemaker therapy over long-term follow-up. Closer monitoring of progressive conduction system disease in BAV patients may be warranted.

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.

An International Multicenter Evaluation of Inheritance Patterns, Arrhythmic Risks, and Underlying Mechanisms of CASQ2-Catecholaminergic Polymorphic Ventricular Tachycardia.

BACKGROUND: Genetic variants in calsequestrin-2 (CASQ2) cause an autosomal recessive form of catecholaminergic polymorphic ventricular tachycardia (CPVT), although isolated reports have identified arrhythmic phenotypes among heterozygotes. Improved insight into the inheritance patterns, arrhythmic risks, and molecular mechanisms of CASQ2-CPVT was sought through an international multicenter collaboration. METHODS: Genotype-phenotype segregation in CASQ2-CPVT families was assessed, and the impact of genotype on arrhythmic risk was evaluated using Cox regression models. Putative dominant CASQ2 missense variants and the established recessive CASQ2-p.R33Q variant were evaluated using oligomerization assays and their locations mapped to a recent CASQ2 filament structure. RESULTS: A total of 112 individuals, including 36 CPVT probands (24 homozygotes/compound heterozygotes and 12 heterozygotes) and 76 family members possessing at least 1 presumed pathogenic CASQ2 variant, were identified. Among CASQ2 homozygotes and compound heterozygotes, clinical penetrance was 97.1% and 26 of 34 (76.5%) individuals had experienced a potentially fatal arrhythmic event with a median age of onset of 7 years (95% CI, 6-11). Fifty-one of 66 CASQ2 heterozygous family members had undergone clinical evaluation, and 17 of 51 (33.3%) met diagnostic criteria for CPVT. Relative to CASQ2 heterozygotes, CASQ2 homozygote/compound heterozygote genotype status in probands was associated with a 3.2-fold (95% CI, 1.3-8.0; P=0.013) increased hazard of a composite of cardiac syncope, aborted cardiac arrest, and sudden cardiac death, but a 38.8-fold (95% CI, 5.6-269.1; P<0.001) increased hazard in genotype-positive family members. In vitro turbidity assays revealed that p.R33Q and all 6 candidate dominant CASQ2 missense variants evaluated exhibited filamentation defects, but only p.R33Q convincingly failed to dimerize. Structural analysis revealed that 3 of these 6 putative dominant negative missense variants localized to an electronegative pocket considered critical for back-to-back binding of dimers. CONCLUSIONS: This international multicenter study of CASQ2-CPVT redefines its heritability and confirms that pathogenic heterozygous CASQ2 variants may manifest with a CPVT phenotype, indicating a need to clinically screen these individuals. A dominant mode of inheritance appears intrinsic to certain missense variants because of their location and function within the CASQ2 filament structure.

Loss of ventricular preexcitation during noninvasive testing does not exclude high-risk accessory pathways: A multicenter study of WPW in children.

BACKGROUND: Abrupt loss of ventricular preexcitation on noninvasive evaluation, or nonpersistent preexcitation, in Wolff-Parkinson-White syndrome (WPW) is thought to indicate a low risk of life-threatening events. OBJECTIVE: The purpose of this study was to compare accessory pathway (AP) characteristics and occurrences of sudden cardiac arrest (SCA) and rapidly conducted preexcited atrial fibrillation (RC-AF) in patients with nonpersistent and persistent preexcitation. METHODS: Patients 21 years or younger with WPW and invasive electrophysiology study (EPS) data, SCA, or RC-AF were identified from multicenter databases. Nonpersistent preexcitation was defined as absence/sudden loss of preexcitation on electrocardiogram, Holter monitoring, or exercise stress test. RC-AF was defined as clinical preexcited atrial fibrillation with shortest preexcited R-R interval (SPERRI) ≤ 250 ms. AP effective refractory period (APERP), SPERRI at EPS , and shortest preexcited paced cycle length (SPPCL) were collected. High-risk APs were defined as APERP, SPERRI, or SPPCL ≤ 250 ms. RESULTS: Of 1589 patients, 244 (15%) had nonpersistent preexcitation and 1345 (85%) had persistent preexcitation. There were no differences in sex (58% vs 60% male; P=.49) or age (13.3±3.6 years vs 13.1±3.9 years; P=.43) between groups. Although APERP (344±76 ms vs 312±61 ms; P<.001) and SPPCL (394±123 ms vs 317±82 ms; P<.001) were longer in nonpersistent vs persistent preexcitation, there was no difference in SPERRI at EPS (331±71 ms vs 316±73 ms; P=.15). Nonpersistent preexcitation was associated with fewer high-risk APs (13% vs 23%; P<.001) than persistent preexcitation. Of 61 patients with SCA or RC-AF, 6 (10%) had nonpersistent preexcitation (3 SCA, 3 RC-AF). CONCLUSION: Nonpersistent preexcitation was associated with fewer high-risk APs, though it did not exclude the risk of SCA or RC-AF in children with WPW.

Difficulties with invasive risk stratification performed under anesthesia in pediatric Wolff-Parkinson-White Syndrome.

BACKGROUND: Children with Wolff-Parkinson-White Syndrome (WPW) are at risk for sudden death. The gold standard for risk stratification in this population is the shortest pre-excited RR interval during atrial fibrillation (SPERRI). OBJECTIVE: The purpose of this study was to determine how closely measurements made in the electrophysiology laboratory in patients with WPW compared to SPERRI obtained during an episode of clinical pre-excited atrial fibrillation (Clinical-SPERRI). METHODS: This was a subgroup analysis of a multicenter study of children with WPW. Subjects in our study (N = 49) were included if they had Clinical-SPERRI measured in addition to 1 or more of 3 surrogate measurements: SPERRI obtained during electrophysiological study (EP-SPERRI), accessory pathway effective refractory period (APERP), or shortest pre-excited paced cycle length with 1:1 conduction (SPPCL). RESULTS: Seventy percent of electrophysiological measurements were made with patients under general anesthesia. Clinical-SPERRI moderately correlated with EP-SPERRI (r = 0.495; P = .012). However, 24% of our patients with Clinical-SPERRI ≤250 ms would have been misclassified as having a low-risk pathway based on EP-SPERRI >250 ms. Clinical-SPERRI did not correlate with APERP or SPPCL (r < 0.3; P >.1). Mean EP-SPERRI, APERP, and SPPCL all were greater than Clinical-SPERRI. CONCLUSION: Electrophysiology laboratory measurements of pathway characteristics made with patients under general anesthesia do not correlate well with Clinical-SPERRI. Of APERP, SPPCL, and EP-SPERRI, only EP-SPERRI had moderate correlation with Clinical-SPERRI. This study questions the predictive ability of invasive risk stratification with patients under general anesthesia, given that 24% of patients with high-risk Clinical-SPERRI (≤250 ms) had EP-SPERRI that may be considered low risk (>250 ms).

Transesophageal 3-Dimensional Echocardiographic Guidance for Pacemaker Lead Placement.

The feasibility of transesophageal 3-dimensional echocardiography to reduce fluoroscopy in pacemaker lead placement has not yet been evaluated. This clinical vignette demonstrates the ability of 3-dimensional echocardiography to visualize intracardiac anatomy and the pacemaker lead and to guide positioning of the lead into the right atrial appendage, thus reducing fluoroscopy by nearly 50%. (Level of Difficulty: Advanced.).

Intraoperative Epicardial Triventricular Pacing in a Pediatric Patient.

Cardiac resynchronization therapy (CRT) is used as an adjunctive therapy in adults with advanced heart failure but remains less commonly applied in pediatric patients. Further, CRT is traditionally conducted via biventricular transvenous pacing from the right ventricle and coronary sinus to activate the left ventricle and improve electromechanical synchrony; however, triventricular pacing, in which a third ventricular lead is utilized to activate an additional ventricular location, has been shown to be a feasible therapeutic alternative to typical CRT in patients with advanced heart failure or nonresponders. Limited adult studies involving triventricular pacing have been performed to date but no pediatric data are available. Thus, we present the case of a 12-month-old patient with congenital complete heart block and subsequent pacemaker-induced cardiomyopathy in whom triventricular epicardial pacing was applied in an effort to increase the available knowledge.