Immediate and Intermediate-Term Effects of Disease Mitigation Measures on Activity Levels as Measured by Implantable Cardiac Devices.

Routine activities of daily living are known to effect overall wellbeing, cardiovascular health, and quality of life. A decrease in daily activity level is recognized as a contributing factor to increasing rates of obesity and a decline in overall health. This study sought to evaluate the effect of disease mitigation strategies on activity level by evaluating changes in recorded cardiac parameters as measured by implantable cardiac devices for a period of time prior to and following implementation of COVID-19 mitigation efforts in Arizona. A retrospective cohort study of cardiac device data from January 1, 2019-December 31, 2020 was performed. Linear mixed-effects models with restricted maximum likelihood estimation were utilized to test for the fixed effects of Year, day, and the interaction between them. A significant decrease in daily activity minutes, daytime heart rates, and heart rate variability coincident with the initiation of disease mitigation strategies was observed. An increase in nighttime heart rates also coincided with initiation of disease mitigation strategies. These effects were noted to persist through the end of the study period. Implementation of statewide disease mitigation strategies resulted in both immediate and intermediate-term effects on activity levels, day and nighttime heart rates trends, and heart rate variability in patients with implanted cardiac devices. These data may serve useful in counseling patients regarding the importance of activity, movement, and exercise to routine health and encourage a return to pre-pandemic levels of activity.

Thoracoscopic Cardiac Sympathetic Denervation: Adjunct Therapy for Secondary Prevention of Life-Threatening Ventricular Arrhythmias in Children.

BACKGROUND: Cardiac sympathetic denervation (CSD) is a surgical option for patients with life-threatening ventricular arrhythmias. Previously described cohorts included populations in which CSD was performed for primary and secondary prevention. We report the efficacy of CSD as adjunct therapy in children with medically refractory life-threatening arrhythmias. MATERIALS AND METHODS: Retrospective review of patients undergoing thoracoscopic CSD at one institution between January 2008 and July 2017. Patient demographics, indications, procedural details, complications, length of stay, and effectiveness were evaluated. RESULTS: Ten thoracoscopic CSD procedures were performed in 8 patients. Mean age was 8.2 years (8 days-19 years); mean weight was 32.6 kg (2.7-57 kg); and 50% were female. Four had long QT syndrome, 3 catecholaminergic polymorphic ventricular tachycardia, and 1 short QT syndrome. All patients had at least two (2 to >40) episodes of resuscitated ventricular arrhythmia and were maximized on medical therapy. Six patients had implantable cardioverter-defibrillators (ICD) with a mean of 11.9 appropriate discharges (1-40) before CSD. All patients underwent left CSD; 2 subsequently required right CSD. Four of the 6 ICD patients experienced dramatic improvement (total 48 ICD discharges pre-CSD; 3 post-CSD). Two patients noncompliant with medical therapy had no significant improvement (24 ICD discharges pre-CSD; 23 post-CSD) and also underwent right CSD, again with no improvement (23 discharges pre-right CSD; 28 post-right CSD). CONCLUSIONS: Thoracoscopic CSD can be safely performed in the neonate and pediatric populations. When utilized with medication therapy, CSD is an effective adjunct in reducing ICD discharges and arrhythmias.

A Clinical Risk Score to Improve the Diagnosis of Tachycardia-Induced Cardiomyopathy in Childhood.

Tachycardia-induced cardiomyopathy (TIC) is a treatable cause of heart failure in children, but there is little information as to which clinical variables best discriminate TIC from other forms of cardiomyopathy. TIC cases with dilated cardiomyopathy (DC) from 16 participating centers were identified and compared with controls with other forms of DC. Presenting clinical, echocardiographic, and electrocardiographic characteristics were collected. Heart rate (HR) percentile was defined as HR/median HR for age, and PR index as the PR/RR interval. P-wave morphology (PWM) was defined as possible sinus or nonsinus based on a predefined algorithm. Eighty TIC cases and 135 controls were identified. Cases demonstrated lower LV end-diastolic diameter and LV end-systolic diameter than DC controls (4.3 vs 6.5, p <0.001; 7.4 vs 10.9, p <0.001) and were less likely to receive inotropic medication at presentation (p <0.001 for both). Multivariable logistic regression identified HR percentile (OR 2.1 per 10% increase, CI 1.3 to 4.6; p = 0.014), PR index (OR 1.2, CI 1.1 to 1.4; p = 0.004), and nonsinus PWM (OR 104.9, CI 15.2 to 1,659.8; p <0.001) as predictive of TIC status. A risk score using HR percentile >130%, PR index >30%, and nonsinus PWM was associated with a sensitivity of 100% and specificity of 87% for the diagnosis of TIC. Model training and validation area under the curves were similar at 0.97 and 0.94, respectively. In conclusion, pediatric TIC may be accurately discriminated from other forms of DC using simple electrocardiographic parameters. This may allow for rapid diagnosis and early treatment of this condition.

Catheter ablation of supraventricular tachyarrhythmia after extracardiac Fontan surgery.

BACKGROUND: Extracardiac total cavopulmonary connection (E-TCPC) is widely performed for single ventricle palliation, yet there is little experience with catheter ablation in this population. OBJECTIVES: We hypothesized that atrial tachycardia substrates after primary E-TCPC would be similar to those in other forms of congenital heart disease and that catheter ablation could be performed effectively using a primarily transconduit approach. METHODS: Catheter ablation characteristics of patients with E-TCPC from 9 centers were collected. Acute procedural success was defined as elimination of all sustained supraventricular tachyarrhythmias. Procedural complications, acute success, and recurrences were assessed. RESULTS: Forty-six catheter ablation procedures were performed in 36 patients. Access to the atrium was by transconduit puncture in 29 procedures (63%). The most common supraventricular tachyarrhythmia mechanism was intra-atrial reentrant tachycardia (IART) in 21 patients (58%); and for all patients with primary E-TCPC and IART, an isthmus between the atrioventricular valve annulus and the oversewn inferior vena cava was critical for maintenance of tachycardia. Overall, acute success was achieved in 38 procedures (83%). There were 8 complications, with only 1 requiring intervention (epicardial pacemaker) and none related to conduit puncture. Recurrence after the final procedure occurred in 6 patients (17%) over a median follow-up duration of 0.4 years (interquartile range 0.1-1.5 years). CONCLUSION: Catheter ablation could be performed effectively in this group of patients with E-TCPC, and the underlying IART substrate after primary E-TCPC appears to be reproducible. Catheter ablation may be a reasonable alternative to long-term antiarrhythmic therapy in this patient group.

Spectrum and Prevalence of CALM1-, CALM2-, and CALM3-Encoded Calmodulin Variants in Long QT Syndrome and Functional Characterization of a Novel Long QT Syndrome-Associated Calmodulin Missense Variant, E141G.

BACKGROUND: Calmodulin (CaM) is encoded by 3 genes, CALM1, CALM2, and CALM3, all of which harbor pathogenic variants linked to long QT syndrome (LQTS) with early and severe expressivity. These LQTS-causative variants reduce CaM affinity to Ca(2+) and alter the properties of the cardiac L-type calcium channel (CaV1.2). CaM also modulates NaV1.5 and the ryanodine receptor, RyR2. All these interactions may play a role in disease pathogenesis. Here, we determine the spectrum and prevalence of pathogenic CaM variants in a cohort of genetically elusive LQTS, and functionally characterize the novel variants. METHODS AND RESULTS: Thirty-eight genetically elusive LQTS cases underwent whole-exome sequencing to identify CaM variants. Nonsynonymous CaM variants were over-represented significantly in this heretofore LQTS cohort (13.2%) compared with exome aggregation consortium (0.04%; P<0.0001). When the clinical sequelae of these 5 CaM-positive cases were compared with the 33 CaM-negative cases, CaM-positive cases had a more severe phenotype with an average age of onset of 10 months, an average corrected QT interval of 676 ms, and a high prevalence of cardiac arrest. Functional characterization of 1 novel variant, E141G-CaM, revealed an 11-fold reduction in Ca(2+)-binding affinity and a functionally dominant loss of inactivation in CaV1.2, mild accentuation in NaV1.5 late current, but no effect on intracellular RyR2-mediated calcium release. CONCLUSIONS: Overall, 13% of our genetically elusive LQTS cohort harbored nonsynonymous variants in CaM. Genetic testing of CALM1-3 should be pursued for individuals with LQTS, especially those with early childhood cardiac arrest, extreme QT prolongation, and a negative family history.

Management of pediatric tachyarrhythmias on mechanical support.

BACKGROUND: Pediatric patients with persistent arrhythmias may require mechanical cardiopulmonary support. We sought to classify the population, spectrum, and success of current treatment strategies. METHODS AND RESULTS: A multicenter retrospective chart review was undertaken at 11 sites. Inclusion criteria were (1) patients <21 years, (2) initiation of mechanical support for a primary diagnosis of arrhythmias, and (3) actively treated on mechanical support. A total of 39 patients were identified with a median age of 5.5 months and median weight of 6 kg. A total of 69% of patients were cannulated for supraventricular tachycardia with a median rate of 230 beats per minute. A total of 90% of patients were supported with extracorporeal membrane oxygenation for an average of 5 days. The remaining 10% were supported with ventricular assist devices for an average of 38 (20-60) days. A total of 95% of patients were treated with antiarrhythmics, with 43% requiring >1 antiarrhythmic. Amiodarone was the most frequently used medication alone or in combination. A total of 33% patients underwent electrophysiology study/transcatheter ablation. Radiofrequency ablation was successful in 9 patients on full flow extracorporeal membrane oxygenation with 3 radiofrequency-failures/conversion to cryoablation. One patient underwent primary cryoablation. A total of 15% of complications were related to electrophysiology study/ablation. At follow-up, 23 patients were alive, 8 expired, and 8 transplanted. CONCLUSIONS: Younger patients were more likely to require support in the presented population. Most patients were treated with antiarrhythmics and one third required electrophysiology study/ablation. Radiofrequency ablation is feasible without altering extracorporeal membrane oxygenation flows. There was a low frequency of acute adverse events in patients undergoing electrophysiology study/ablation, while on extracorporeal membrane oxygenation.

Predictors of myocardial recovery in pediatric tachycardia-induced cardiomyopathy.

BACKGROUND: Tachycardia-induced cardiomyopathy (TIC) carries significant risk of morbidity and mortality, although full recovery is possible. Little is known about the myocardial recovery pattern. OBJECTIVE: The purpose of this study was to determine the time course and predictors of myocardial recovery in pediatric TIC. METHODS: An international multicenter study of pediatric TIC was conducted. Children ≤18 years with incessant tachyarrhythmia, cardiac dysfunction (left ventricular ejection fraction [LVEF] <50%), and left ventricular (LV) dilation (left ventricular end-diastolic dimension [LVEDD] z-score ≥2) were included. Children with congenital heart disease or suspected primary cardiomyopathy were excluded. Primary end-points were time to LV systolic functional recovery (LVEF ≥55%) and normal LV size (LVEDD z-score <2). RESULTS: Eighty-one children from 17 centers met inclusion criteria: median age 4.0 years (range 0.0-17.5 years) and baseline LVEF 28% (interquartile range 19-39). The most common arrhythmias were ectopic atrial tachycardia (59%), permanent junctional reciprocating tachycardia (23%), and ventricular tachycardia (7%). Thirteen required extracorporeal membrane oxygenation (n = 11) or ventricular assist device (n = 2) support. Median time to recovery was 51 days for LVEF and 71 days for LVEDD. Two (4%) underwent heart transplantation, and 1 died (1%). Multivariate predictors of LV systolic functional recovery were age (hazard ratio [HR] 0.61, P = .040), standardized tachycardia rate (HR 1.16, P = .015), mechanical circulatory support (HR 2.61, P = .044), and LVEF (HR 1.33 per 10% increase, p=0.005). For normalization of LV size, only baseline LVEDD (HR 0.86, P = .008) was predictive. CONCLUSION: Pediatric TIC resolves in a predictable fashion. Factors associated with faster recovery include younger age, higher presenting heart rate, use of mechanical circulatory support, and higher LVEF, whereas only smaller baseline LV size predicts reverse remodeling. This knowledge may be useful for clinical evaluation and follow-up of affected children.

The Multicenter Pediatric and Adult Congenital EP Quality (MAP-IT) Initiative-rationale and design: report from the pediatric and congenital electrophysiology society's MAP-IT taskforce.

Multicenter clinical registries are increasingly recognized as valuable tools for establishing benchmarks, facilitating patient-centered quality improvement and research. In 2010, the Pediatric and Congenital Electrophysiology Society convened a taskforce of its members to design, construct, and implement a clinical registry known as the Multicenter Pediatric and Adult Congenital EP Quality (MAP-IT) Initiative. The present aim of the MAP-IT Initiative is to create an infrastructure by which we can measurably improve patient-centered outcomes and reduce complications associated with electrophysiology studies and catheter ablation in pediatric and congenital heart disease patients. The purpose of this writing is to report the progress to date from three of the four subcommittees of the MAP-IT taskforce. Specifically, we present our initial set of key data elements and definitions, recommended database table structure, and considerations regarding wide-scale implementation of the registry. Development of a risk/complexity score for use in the MAP-IT registry is presented in a separate companion manuscript. It is our intent that these manuscripts will serve to introduce the electrophysiology and pediatric cardiology community to the MAP-IT initiative and provide a rationale for its design and recommended implementation strategy.

Unusually high association of hypertrophic cardiomyopathy and complex heart defects in children with fasciculoventricular pathways.

INTRODUCTION: Fasciculoventricular pathways (FVPs) are rare causes of preexcitation that do not mediate tachycardias. We report a two-center experience of pediatric patients with FVP and an unexpectedly high association of complex congenital heart defects (CHDs), chromosomal anomalies, and hypertrophic cardiomyopathy. METHODS: A retrospective review of the electrophysiology database at two institutions was performed to identify patients with FVP from January 2000 to January 2011. Medical records of these patients were reviewed for clinical history and course, presence of comorbidities, and details of intracardiac electrophysiology (EP) study. RESULTS: A total of 17 patients were identified. The primary indication for EP study was a preexcitation pattern on electrocardiogram. The majority of patients, 12/17 (71%), were found to have associated cardiac and genetic anomalies. Hypertrophic cardiomyopathy was found in 5/17 (29%) patients, with genetic testing in two patients demonstrating the lysosomal-associated membrane protein 2 mutation (Danon syndrome). Underlying complex CHDs were present in 3/17 (18%) patients. One patient (6%) was status post (s/p) cardiac transplant, one patient had hypertension, and another had Trisomy 21. Other electrophysiologic substrates mediating tachycardia were found in 3/17 (18%) patients. Only 5/17 patients (29%) were otherwise healthy with structurally normal hearts. CONCLUSIONS: In this largest reported series of FVP in children, there is an unusually high association of FVP with complex CHDs, chromosomal anomalies, and hypertrophic cardiomyopathy. Any patient with such disorders and manifest preexcitation should be evaluated with a high index of suspicion for a FVP.

Limited utility of exercise-stress testing to prevent T-wave oversensing in pediatric internal cardioverter defibrillator recipients.

BACKGROUND: Inappropriate internal cardioverter defibrillator (ICD) therapies may result from T-wave oversensing (TWOS) during exertion in children. The aim of this study was to evaluate the utility of an exercise treadmill test to predict inappropriate ICD therapies secondary to TWOS. METHODS: Eligible pediatric ICD recipients underwent exercise-stress testing with concomitant evaluation of all intracardiac electrograms. Double counting at a programmed sensitivity of 0.3 mV was considered indicative of TWOS. Patients were prospectively followed for 2 years and censored at either the development of an inappropriate ICD therapy secondary to TWOS or at the time of ICD revision. RESULTS: Nineteen patients (age: 13.8 ± 3.2 years) underwent exercise testing (median time from ICD implant: 1.5 years, range 2-4.3 years). Two patients were identified with TWOS during the stress test and had a clinically inappropriate ICD discharge within 2 weeks despite a sensitivity adjustment to 0.6 mV. One individual had an inappropriate ICD discharge from TWOS 11 months following an initial uneventful exercise-stress test. CONCLUSIONS: Inappropriate ICD therapies from TWOS relate to a reduction in the intrinsic R wave or augmentation of the T wave during exertion. While intracardiac electrogram assessment during stress testing may aid in the early recognition of TWOS, it did not absolutely translate to a reduction in the incidence of inappropriate ICD shocks.

An unusual resolution of T-wave oversensing in an implantable cardioverter defibrillator in a child with long QT syndrome.

T-wave oversensing poses a clinical challenge often resulting in inappropriate therapies and shocks. T-wave oversensing can often be resolved by certain programmable adjustments while accepting a small risk of undersensing ventricular fibrillation. The following case depicts a girl with LQT whose transvenous defibrillator repeatedly demonstrated T-wave oversensing despite optimizing various programmable features and a separate pace/sense lead. Utilization of an LV epicardial pace/sense lead with stable R-waves affirmed an unusual resolution of T-wave oversensing and avoidance of inappropriate shocks.

Impact of a computer assisted navigation system on radiation exposure during pediatric ablation procedures.

BACKGROUND: During catheter ablation procedures, non-radiologic navigation systems may reduce fluoroscopic exposure and energy applications, as well as improve procedural success rates. OBJECTIVE: To examine the impact of a non-radiologic navigation system on ablation procedures in pediatric patients, the procedural characteristics and success rates prior to and following incorporation of the LocaLisa (LL) navigation system into a pediatric electrophysiology laboratory were compared. METHODS: Between January 2000 and April 2005, 246 consecutive patients underwent catheter ablation for either Atrioventricular Reentry Tachycardia AVRT (168) or Atrioventricular Nodal Reentry Tachycardia AVNRT (78). Ablation procedures performed prior to LL (108) were compared to ablation procedures performed using LL (113). The first 25 patients using LL were censored to remove the bias of a learning curve. RESULTS: There was no difference in demographic features between the two groups. Statistically significant decreases were found in the diagnostic (11.4 +/- 6.1 min v 18.8 +/- 9.8 min w/o LL), ablation (5.7 +/- 10.3 vs 18.5 +/- 20.1 min w/o LL) and total (17.2 +/- 12.6 vs 37.3 +/- 21.3 min w/o LL) fluoroscopy times for the LL group, as well as in the total number of energy applications (9.0 +/- 8.5 vs 12.3 +/- 12.2 w/o LL). Success rates were 99.1% w/ LL v 97.2% w/o LL (p = NS). No major complications were observed in either group. CONCLUSIONS: The use of a computer assisted navigation system significantly decreased the diagnostic, ablation, and total fluoroscopy times, as well as the number of energy applications, without affecting procedural success or complication rates. Non-radiologic navigation systems reduce radiation exposure during transcatheter electrophysiologic procedures and thus lower the lifetime radiation cumulative risk, a goal particularly important in children.

Transcatheter cryotherapy for the treatment of supraventricular tachyarrhythmias in children: a single center experience.

INTRODUCTION: Transcatheter cryotherapy is an emerging technology for the treatment of children with supraventricular tachyarrhythmias. Limited data exist regarding the use of cryoablation therapy in children. We report a single center's experience with transcatheter cryoablation in the pediatric population. METHODS AND RESULTS: A retrospective review of demographic, procedural and outcome data was performed for patients undergoing cryoablation for treatment of supraventricular tachycardia (SVT). A historical control group was taken from the 3 years preceding the introduction of cryoablation. Between August 2003 and November 2005, 83 cryoablation procedures were performed in 81 patients (age: 4 to 21 years, mean: 13.4 years) for AV nodal reentrant tachycardia (AVNRT--53), AV reentrant tachycardia (AVRT--20), ectopic atrial tachycardia (EAT--9), and junctional ectopic tachycardia (JET--1). The acute success rate for all procedures was 88% (AVNRT: 96%, AVRT: 85%, EAT: 55%, and JET: 100%). Of 72 patients that underwent successful cryoablation, nine experienced recurrence of SVT (12.5%). The control group consisted of 73 patients (AVNRT--60, AVRT--13). There were no differences in demographic data between the two groups. The overall success rate for the RFA group (96%) was identical to that for patients with AVNRT and AVRT undergoing cryoablation. The recurrence rate for RFA (10%) was less but not significantly different than that for cryoablation (12%). There were no complications in either group. CONCLUSIONS: Cryoablation is a safe and effective alternative for the treatment of SVT in children.