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.

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.

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.

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.

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.