The clinical and genetic spectrum of catecholaminergic polymorphic ventricular tachycardia: findings from an international multicentre registry.

Aims: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an ion channelopathy characterized by ventricular arrhythmia during exertion or stress. Mutations in RYR2-coded Ryanodine Receptor-2 (RyR2) and CASQ2-coded Calsequestrin-2 (CASQ2) genes underlie CPVT1 and CPVT2, respectively. However, prognostic markers are scarce. We sought to better characterize the phenotypic and genotypic spectrum of CPVT, and utilize molecular modelling to help account for clinical phenotypes. Methods and results: This is a Pediatric and Congenital Electrophysiology Society multicentre, retrospective cohort study of CPVT patients diagnosed at <19 years of age and their first-degree relatives. Genetic testing was undertaken in 194 of 236 subjects (82%) during 3.5 (1.4-5.3) years of follow-up. The majority (60%) had RyR2-associated CPVT1. Variant locations were predicted based on a 3D structural model of RyR2. Specific residues appear to have key structural importance, supported by an association between cardiac arrest and mutations in the intersubunit interface of the N-terminus, and the S4-S5 linker and helices S5 and S6 of the RyR2 C-terminus. In approximately one quarter of symptomatic patients, cardiac events were precipitated by only normal wakeful activities. Conclusion: This large, multicentre study identifies contemporary challenges related to the diagnosis and prognostication of CPVT patients. Structural modelling of RyR2 can improve our understanding severe CPVT phenotypes. Wakeful rest, rather than exertion, often precipitated life-threatening cardiac events.

Analysis of Screening Electrocardiogram for the Subcutaneous Defibrillator in Adults with Congenital Heart Disease.

Candidates for the subcutaneous implantable cardioverter-defibrillator (S-ICD) are screened using an electrocardiogram (S-ECG) tool to measure appropriate detection. We sought to define the S-ICD candidacy of congenital heart disease patients using the S-ECG tool. We also analyzed the reliability of the (S-ECG) tool between measurers in this population. Patients above the age of 12 and with a diagnosis associated with either a higher incidence of cardiac arrest or vascular access challenges were asked to undergo screening. S-ECGs were then analyzed by a pediatric electrophysiologist, an S-ICD device engineer, and an S-ICD clinical representative for candidacy. Results were compared for interobserver variability and S-ECGs were analyzed by t test to determine variables that differ among passing and failing leads. Thirty-one patients underwent screening. Two of the 31 (6.5%) patients failed S-ICD screening. Analysis of the screening leads demonstrated the highest passing rates using lead III at a 5 mm/mV amplitude setting with 71 and 62% pass rate in the supine and standing positions, respectively. Interobserver analysis correlated well among the three measurers. There was a higher amplitude difference between QRS and T waves among passing versus failing S-ECG. Congenital heart disease patients have acceptable passage rates utilizing the S-ECG algorithm. Interobserver measurements were well correlated and these data suggest that the proximal coil to device (lead III) vector would be best utilized in this patient population. A larger difference between QRS and T wave amplitudes was associated with a higher S-ECG passing rate.

Attention deficit hyperactivity disorder screening electrocardiograms: a community-based perspective.

Screening electrocardiograms (EKGs) for attention deficit hyperactivity disorder (ADHD) medication administration is controversial. We reviewed our experience as a community-based cardiology group. We reviewed all ADHD screening EKGs during a 2-year period. We evaluated whether screening EKGs resulted in further consultation and if management was altered. We also evaluated differences between patients on ADHD medications and those starting ADHD medications and further stratified the patients into stimulant versus nonstimulant groups. A total of 691 screening EKGs met our criteria. Forty-two patients (6.1%) were recommended for further consultation. EKG findings requiring consultation included the following: left-ventricular hypertrophy, right atrial enlargement, arrhythmia, prolonged QT, and axis deviation. Studies performed during consultation included 39 echocardiograms, 2 stress tests, 2 Holter monitors, and 1 heart card. Five patients (0.72%) were identified to have cardiac disease, one of whom decided against starting ADHD medications due to an arrhythmia, resulting in a change in management (0.14%). Results comparing mean age, heart rate, and corrected QT interval between patients on medication and patients starting medications were as follows: 10.06 years, 82.87, bpm and 405.24 ms compared with 9.99 years, 80.05 bpm, and 405.82 ms, respectively (p = not significant [NS], p = 0.013 [NS], respectively). Results comparing mean age, heart rate, and corrected QT interval between patients on stimulant versus nonstimulant medications were as follows: 9.68 years, 83.10 bpm, and 403.04 ms compared with 9.81 years, 80.10 bpm, and 407.08 ms, respectively (p = NS for all). In our population, screening EKGs rarely resulted in management changes for patients taking or starting ADHD medications.

Racial/ethnic and sex differences in safety outcomes and atrial fibrillation/atrial flutter-related acute healthcare utilization after catheter ablation of atrial fibrillation.

Background: Catheter ablation is recommended for the treatment of symptomatic atrial fibrillation (AF) refractory to medical therapy. Objective: The study sought to examine racial/ethnic and sex differences in complications and AF/atrial flutter (AFL)-related acute healthcare utilization following catheter ablation for AF. Methods: We performed a retrospective analysis using data from the Centers for Medicare and Medicaid Services Medicare Standard Analytical Files (October 1, 2014, to September 30, 2019) among patients ≥65 years of age with AF who underwent catheter ablation for rhythm control. The risk of any complication within 30 days and AF/AFL-related acute healthcare utilization within 1 year of ablation by race, ethnicity, and sex were assessed using multivariable Cox regression modeling. Results: We identified 95,394 patients for analysis of postablation complications and 68,408 patients for analysis of AF/AFL-related acute healthcare utilization. Both cohorts were ∼95% White and 52% male. Female patients had a slightly elevated risk of complications compared with male patients (adjusted hazard ratio [aHR] 1.07, 95% confidence interval [CI] 1.03-1.12). Black (aHR 0.78, 95% CI 0.77-1.00) and Asian (aHR 0.67, 95% CI 0.50-0.89) patients had lower utilization compared with White patients. Specifically, Asian men (aHR 0.58, 95% CI 0.38-0.91) had lower utilization compared with White men. Conclusion: Differences in safety and healthcare utilization after catheter ablation for AF were observed by race/ethnicity and sex groups. Underrepresented racial and ethnic groups with AF had a lower risk of AF/AFL-related acute healthcare utilization postablation.

Race and Ethnic and Sex Differences in Rhythm Control Treatment of Incident Atrial Fibrillation.

Background: Atrial fibrillation (AF) is associated with considerable morbidity and mortality. Timely management and treatment is critical in alleviating AF disease burden. Variation in treatment by race and ethnic and sex could lead to inequities in health outcomes. Objective: To identify racial and ethnic and sex differences in rhythm treatment for patients with incident AF. Methods: Using 2010-2019 Optum Clinformatics database, an administrative claims data for commercially insured patients in the United States (US), incident AF patients ≥20 years old who were continuously enrolled 12-months pre- and post-index diagnosis were identified. Rhythm control treatment (ablation, antiarrhythmic drugs [AAD], and cardioversion) for AF were compared by patient race and ethnicity (Asian, Hispanic, Black vs White) and sex (female vs male). Multivariable regression analysis was used to examine the relationship of race and ethnicity and sex with rhythm control AF treatment. Results: A total of 77,932 patients were identified with incident AF. Black and Hispanic female patients had the highest CHA2DS2VASc scores (4.3 ± 1.8) and Elixhauser scores (4.1 ± 2.8 and 4.0 ± 6.7), respectively. Black males were less likely to receive AAD treatment (adjusted odds ratio [aOR] 0.87; 95% confidence interval [CI], 0.79-0.96) or ablation (aOR, 0.72; 95% CI, 0.58-0.90). Compared to White males, all groups had lower likelihood of receiving cardioversion with Asian females having the lowest [aOR, 0.48; 95% CI, (0.37-0.63)]. Conclusion: Black patients were less likely to receive pharmacologic and procedural rhythm control therapies. Further research is needed to understand the drivers of undertreatment among racial and ethnic groups and females with AF.

Cardioversion of intraatrial reentrant tachycardia using rate response.

Intraatrial reentrant tachycardia (IART) is the most common long-term, surgical arrhythmia sequela in patients with complex congenital heart disease. The management of IART is challenging. Medications, catheter ablation therapy, and pacemaker therapy have all been utilized as treatment options. Slower tachycardia cycle lengths and 1:1 atrioventricular conduction provide even more challenges with regard to detection and antitachycardia pacing. We describe the use of the rate response feature as a means of patient-initiated cardioversion.

The low specificity of low voltage bridges associating atrioventricular nodal reentry in pediatric patients.

PURPOSE: Patients with atrioventricular nodal reentry tachycardia (AVNRT) often are managed successfully by ablation of the slow pathway with success rates reported as high as 99%. Low voltage bridges (LVBs) have been demonstrated to be helpful in guiding AVNRT ablation. Patients may present to the electrophysiology lab without evidence of inducible arrhythmia. In these scenarios, the demonstration of LVBs may be diagnostic and guide catheter ablation treatment. The purpose of our study was to prospectively investigate the specificity of LVBs as a diagnostic marker of AVNRT. METHODS: Patients aged < 19 years with narrow complex tachycardia prospectively underwent electrophysiology study with intention to perform catheter ablation. In each patient, the primary objective was the collection of right atrial voltage data that was then used to identify LVBs. RESULTS: Twenty-four patients were included after exclusion criteria were applied. Final diagnosis was 11 AVNRT and 13 non-AVNRT (nAVNRT). LVBs were identified in 11/11 AVNRT patients and 9/13 non-AVNRT patients (p = 0.09). CONCLUSIONS: LVBs are not specific to patients with AVNRT and cannot solely be used for diagnosis. However, in patients with documented AVNRT, the LVB can be used to identify the location of the slow pathway.

Nonfluoroscopic Ablation in the Setting of Congenital Heart Disease.

In this case series, we demonstrate the performance of nonfluoroscopic ablation in the congenital heart disease population. Techniques for procedural safety and the benefits of three-dimensional mapping in the setting of structural heart disease are reviewed.

Improving Defibrillation Efficiency in Area Schools.

OBJECTIVE: Sudden cardiac arrest (SCA) in the young is a rare event but the effects can be devastating. We sought to identify variables that would lead to an improvement in time to defibrillation (TDFB), a previously noted factor significantly influencing survival from cardiac arrest. DESIGN: During the 2013-2014 academic year, the Clark county school district performed quarterly drills to practice the coordinated automated external defibrillator (AED) response. Variables including school, AED carrier, and drill characteristics were measured to determine influence on TDFB. Schools were grouped by TDFB at a cutoff of three minutes. Characteristics were sought for schools with TDFB below three minutes. A mixed regression model taking into account repeated measures was created to determine which variables influenced TDFB. RESULTS: Time to overhead announcement, distance of AED from drill site, and time to setup AED were the variables influencing TDFB with statistical significance (P <.01). CONCLUSIONS: This study supports the notion of early recognition, announcement, and close proximity to an AED during a SCA to ensure an early TDFB. These results are consistent with basic life support and the chain of survival tenets of the American Heart Association.

Catecholaminergic polymorphic ventricular tachycardia in children: analysis of therapeutic strategies and outcomes from an international multicenter registry.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia is an uncommon, potentially lethal, ion channelopathy. Standard therapies have high failure rates and little is known about treatment in children. Newer options such as flecainide and left cardiac sympathetic denervation are not well validated. We sought to define treatment outcomes in children with catecholaminergic polymorphic ventricular tachycardia. METHODS AND RESULTS: This is a Pediatric and Congenital Electrophysiology Society multicenter, retrospective cohort study of catecholaminergic polymorphic ventricular tachycardia patients diagnosed before 19 years of age. The cohort included 226 patients, including 170 probands and 56 relatives. Symptomatic presentation was reported in 176 (78%). Symptom onset occurred at 10.8 (interquartile range, 6.8-13.2) years with a delay to diagnosis of 0.5 (0-2.6) years. Syncope (P<0.001), cardiac arrest (P<0.001), and treatment failure (P=0.008) occurred more often in probands. ß-Blockers were prescribed in 205 of 211 patients (97%) on medication, and 25% experienced at least 1 treatment failure event. Implantable cardioverter defibrillators were placed in 121 (54%) and was associated with electrical storm in 22 (18%). Flecainide was used in 24% and left cardiac sympathetic denervation in 8%. Six deaths (3%) occurred during a cumulative follow-up of 788 patient-years. CONCLUSIONS: This study demonstrates a malignant phenotype and lengthy delay to diagnosis in catecholaminergic polymorphic ventricular tachycardia. Probands were typically severely affected. ß-Blockers were almost universally initiated; however, treatment failure, noncompliance and subtherapeutic dosing were often reported. Implantable cardioverter defibrillators were common despite numerous device-related complications. Treatment failure was rare in the quarter of patients on flecainide. Left cardiac sympathetic denervation was not uncommon although the indication was variable.

Measures of dyssynchrony in the left ventricle of healthy children and young patients with dilated cardiomyopathy.

BACKGROUND: Doppler tissue imaging may help identify children with dyssynchrony who could benefit from resynchronization therapy. However, few studies have quantified dyssynchrony measures in children; no study has investigated the relationship among age, heart rate, and dyssynchrony measures in children; and no study has quantified cross-correlation delay in children. The aim of this study was to test the hypotheses that measures of left ventricular dyssynchrony would correlate with age, primarily because of the correlation between heart rate and age, and that children with cardiomyopathy would have left ventricular dyssynchrony. METHODS: Sixty healthy children and 11 children with dilated cardiomyopathy were prospectively enrolled. Seven dyssynchrony measures were quantified: septal-to-lateral delay, peak velocity difference, the standard deviations of times to peak in 12 segments in systole and diastole, and cross-correlation delay in systole, diastole, and the whole cycle. RESULTS: The seven dyssynchrony measures were either not correlated with age or only weakly correlated with age after correcting for heart rate using Bazett's formula. Septal-to-lateral delay, peak velocity difference, and the standard deviation of times to peak in 12 segments in systole showed dyssynchrony in 57% to 85% of normal controls, compared with 20% for cross-correlation delay in the whole cycle and 3% for the standard deviation of times to peak in 12 segments in diastole. Cross-correlation delay in systole, cross-correlation delay in diastole, cross-correlation delay in the whole cycle, and the standard deviation of times to peak in 12 segments in diastole were elevated in children with dilated cardiomyopathy compared with controls. CONCLUSIONS: Echocardiographic dyssynchrony measures should be corrected for heart rate using Bazett's formula in children. Time-to-peak Doppler tissue imaging dyssynchrony measures classify many healthy children as having abnormalities with the timing of left ventricular contraction, which suggests that the methodology is not accurate in children. In preliminary studies, cross-correlation dyssynchrony measures show elevated systolic and diastolic measures of dyssynchrony in children with dilated cardiomyopathy compared with controls, which deserves further investigation to help identify children who may benefit from resynchronization therapy.

Transcatheter closure of secundum atrial septal defect in infants less than 12 months of age improves symptoms of chronic lung disease.

OBJECTIVE: Device closure of secundum type atrial septal defects in young children has now become common with extension of this practice to children less than 1 year of age. We hypothesized that patients less than 12 months of age with moderate increases in pulmonary blood flow due to atrial septal defects may improve clinically with device closure, particularly premature infants with chronic lung disease. DESIGN: Thirteen patients under 12 months of age have undergone atrial septal device closure at our institution from March 2002 to July 2008, with evidence of a left to right shunt by pre-procedural echocardiogram. We evaluated concomitant conditions and device closure results. Patient charts from follow-up visits with referring pediatric cardiologists were also reviewed. Follow-up phone interviews were conducted with parents/guardians of patients who underwent device closure to further evaluate clinical change. RESULTS: The patient ages ranged from 3-11 months (median 7) with weight ranges of 2.9-8.3 kg (median 6.5). Defect sizes ranged from 5-15 mm (median 9). Concomitant conditions included prematurity with bronchopulmonary dysplasia (n = 8) and concern of elevated pulmonary artery pressures (n = 5). The median Qp : Qs was 1.6 with a range of 1 to 2.6. The mean pulmonary artery pressures ranged from 16 to 55 mm Hg (median 27). Eleven of 13 patients showed significant improvement in their clinical status, with a reduction in oxygen requirement (six patients) and reduced right heart pressures by echocardiogram (four patients). There were no residual defects on follow-up echocardiograms. CONCLUSION: Transcatheter closure of atrial septal defects in infants can be safe, effective, and may be indicated for situations in which the left to right shunt may be implicated as a cause of ongoing chronic lung disease. Moderate increases in pulmonary blood flow due to atrial septal defects may have a negative clinical impact regarding continuing respiratory insufficiency in these patients.