Utilizing median and maximum QTc values improves prediction of breakthrough cardiac events in pediatric long QT syndrome.

INTRODUCTION: Although prior studies indicate that a QTc > 500 ms on a single baseline 12-lead electrocardiogram (ECG) is associated with significantly increased risk of arrhythmic events in long QT syndrome (LQTS), less is known about the risk of persistent QT prolongation. We sought to determine QTc persistence and its prognostic effect on breakthrough cardiac events (BCEs) among pediatric patients treated for LQTS. METHODS: We performed a retrospective analysis of 433 patients with LQTS evaluated, risk-stratified, and undergoing active guideline-based LQTS treatment between 1999 and 2019. BCEs were defined as arrhythmogenic syncope/seizure, sudden cardiac arrest (SCA), appropriate VF-terminating ICD shock, and sudden cardiac death (SCD). RESULTS: During the median follow-up of 5.5 years (interquartile range [IQR] = 3-9), 32 (7%) patients experienced a total of 129 BCEs. A maximum QTc threshold of 520 ms and median QTc threshold of 490 ms were determined to be strong predictors for BCEs. A landmark analysis controlling for age, sex, genotype, and symptomatic status demonstrated models utilizing both the median QTc and maximum QTc demonstrated the highest discriminatory value (c-statistic = 0.93-0.95). Patients in the high-risk group (median QTc > 490 ms and maximum QTc > 520 ms) had a significantly lower BCE free survival (70%-81%) when compared to patients in both medium-risk (93%-97%) and low-risk (98%-99%) groups. CONCLUSIONS: The risk of BCE among patients treated for LQTS increases not only based upon their maximum QTc, but also their median QTc (persistence of QTc prolongation). Patients with a maximum QTc > 520 ms and median QTc > 490 ms over serial 12-lead ECGs are at the highest risk of BCE while on guideline-directed medical therapy.

Utility of routine follow-up defibrillation safety margin testing in young patients with epicardial implantable cardioverter-defibrillators.

BACKGROUND: Routine defibrillation threshold testing (DFT) of transvenous implantable defibrillators (ICDs) has largely been in decline. In patients with non-transvenous ICDs that utilize subcutaneous and pleural ICD leads, serial DFT testing can detect a significant number of failures. Data about the utility of follow-up defibrillation safety margin testing (DSM) testing in pediatric patients and young adults with an epicardial ICD are lacking. METHODS: Patients aged < 25 years old who underwent epicardial ICD placement at Mayo Clinic from 2014 to 2023 with at least one follow-up DSM test were included. The patients were divided into a "routine" (R) and "clinically indicated" (CI) group based on the index of clinical concern. Inadequate DSM was defined as unsuccessful defibrillation at an output of less than 10 J below the maximum output of the device. The purpose of this study was to assess the utility of follow-up DSM testing. RESULTS: An epicardial ICD system was placed in 122 patients. A total of 26 patients met inclusion criteria and underwent a total of 47 DSM follow up tests. Inadequate DSM occurred in 1/33 (3%) in the R group and 2/14 (14%) DSM tests in the CI group. The median follow-up period was 54 and 36 months for the R and CI group, respectively. CONCLUSIONS: Our data suggest that epicardial ICDs are reliable and routine follow-up DSM testing may not be necessary for all patients. DSM testing should be performed in individuals with epicardial ICD systems when there is clinical concern about lead or coil performance.

Septal Myectomy Outcomes in Children and Adolescents With Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: Little data exist regarding characteristics and outcomes of pediatric patients undergoing septal myectomy. We evaluated this in a large referral population. METHODS: Septal myectomy was performed in 199 consecutive patients aged ≤18 years with obstructive hypertrophic cardiomyopathy from January 1, 1976, to June 30, 2021. RESULTS: Median age was 13 years (interquartile range [IQR], 8-15 years). Left ventricular myectomy approaches included transaortic (163 of 198 [82%]), transapical (16 of 198 [8%]), and combined (19 of 198 [10%]). Right ventricular interventions included myectomy (13 of 199 [7%]) and patch reconstruction of the outflow tract (15 of 199 [8%]). Maximum left ventricular outflow tract gradients decreased after myectomy (prebypass: 50 mm Hg [IQR, 31-73 mm Hg] vs postbypass: 4 mm Hg [IQR, 0-9 mm Hg], P < .001), and this was sustained long-term (5 mm Hg [IQR, 5-10 mm Hg] at 10 years). Iatrogenic aortic and mitral valve injuries occurred in 13 of 199 (7%) and 1 of 199 (1%), respectively; however, all were successfully repaired. Operative mortality was 2 of 199 (1%). The cumulative incidence of redo myectomy was low, at 5.8% at 5 and 8.3% at 10 years. Redo myectomy patients had higher maximum left ventricular outflow tract gradients on echocardiography at predischarge and 1 year and were younger at the index operation (8 years [IQR, 2.5-10 years] vs 13 years [IQR, 9-16 years], P < .001). Overall survival at 10 years was 90%, relative to 47% in a previously reported pediatric nonoperative cohort. CONCLUSIONS: Pediatric septal myectomy provides safe, effective, and durable relief of ventricular outflow tract obstruction. Iatrogenic valve injury remains a low but nonnegligible risk. Recurrent obstruction requiring redo myectomy is infrequent and can be identified early. Long-term survival in this pediatric septal myectomy cohort appears to fare better than pediatric hypertrophic cardiomyopathy cohorts managed nonoperatively.

Pediatric Epicardial Devices: Early and Midterm Outcomes.

BACKGROUND: Lead performance is suboptimal in young patients and a main cause of device system failure. Our objective was to assess early and midterm outcomes after epicardial device implantation in a contemporary pediatric cohort. METHODS: A total of 116 consecutive pediatric patients underwent 137 epicardial device implantations from 2010 to 2019. Forty pacemakers and 97 implantable cardioverter defibrillators (ICDs) were implanted. Lead failure was defined as leads repaired, replaced, or abandoned due to fracture, dislodgement, or dysfunction. Freedom from device system failure was determined using Kaplan-Meier analysis. RESULTS: Mean age at implantation was 10 ± 5 years, 46 (34%) were younger than 8 years old, 41 (30%) had prior cardiac surgery, and 38 (28%) had prior devices. Main indications were acquired heart block (17/40 [43%]), sinus node dysfunction (14/40 [35%]), and congenital heart block (7/40 [18%]) for pacemakers, and hypertrophic cardiomyopathy (46/97 [47%]), long QT syndrome (31/97 [32%]), and ventricular arrhythmia (17/97 [18%]) for ICDs. There were no early deaths. Three-year freedom from device system failure was 80% (95% CI 73%, 88%) for all patients and 88% (95% CI 79%, 99%) for patients <8 years old. Device system failure causes included lead fracture (20/34 [59%]), lead dysfunction (5/34 [15%]), lead dislodgement (5/34 [15%]), infection (3/34 [9%]), and pericarditis (1/34 [3%]). Reintervention was required in 26/34 (76%) device system failures. CONCLUSIONS: Epicardial device implantation is safe, shows acceptable midterm outcomes in children, and is an effective option in patients younger than 8 years old. Close device surveillance continues to be essential to detect lead failure early and ensure timely reintervention.

Asymptomatic Apical Hypertrophic Cardiomyopathy in an Elite Competitive Athlete.

A 17-year-old male elite athlete presented for evaluation after an abnormal pre-competitive college screening electrocardiogram. Subsequent evaluation revealed the presence of hypertrophic cardiomyopathy. He remained asymptomatic throughout four years of follow-up. Through shared decision making, he continued to play competitively and is now a professional athlete. (Level of Difficulty: Advanced.).

Empiric Slow Pathway Cryoablation in Symptomatic Children Without Documented Supraventricular Tachycardia.

In symptomatic children without documented supraventricular tachycardia (SVT) and non-inducible atrioventricular nodal reentry tachycardia (AVNRT) the benefit of empiric slow pathway (SP) ablation is unknown. We evaluated 62 symptomatic patients without documented SVT that underwent electrophysiology study (EPS). The purpose of this study was to determine if symptoms improved after empiric SP ablation in children without documented SVT and without inducible AVNRT. Sixty-two symptomatic patients without previously documented SVT underwent EPS; 31 (50%) had inducible AVNRT and underwent SP ablation, 20 (32%) were non-inducible and underwent empiric SP ablation, 11 (18%) were non-inducible and had no ablation. After a mean follow-up of 23 ± 18 months there was no significant difference in freedom from symptoms within the non-inducible cohort regardless of whether empiric SP ablation was performed (p = 0.135). There was a significant improvement in symptoms at follow-up after SP ablation when comparing inducible and non-inducible patients (p = 0.020). During follow-up no patients had documented SVT. Symptomatic children without documented SVT do not benefit from empiric SP ablation when AVNRT cannot be induced.

Pediatric Electrophysiology Device Needs: A Survey from the Pediatric and Congenital Electrophysiology Society Taskforce on Pediatric-Specific Devices.

Background There are few US Food and Drug Administration (FDA)-approved devices specifically aimed at the pediatric patient with arrhythmia. This has led to a high off-label utilization of devices in this vulnerable population. The Pediatric and Congenital Electrophysiology Society (PACES), the international organization representing pediatric and congenital heart disease arrhythmia specialists, developed a task force to comprehensively address device development issues relevant to pediatric patients with congenital arrhythmia. Methods and Results As a first step, the taskforce developed a 26-question survey for the pediatric arrhythmia community to assess providers' understanding of the FDA approval process, specifically in regard to pediatric labeling. There were 92/211 respondents (44%) with a >90% completion rate. The vast majority of respondents believed there was a paucity of devices available for children (96%). More than 60% of respondents stated that they did not understand the FDA regulatory process and were not aware of whether the devices they used were labeled for pediatric use. Conclusions Pediatric electrophysiologists are keenly aware of the deficit of available pediatric devices for their patients. The majority do not understand the FDA approval process and could benefit from additional educational resources regarding this. A collaborative forum including PACES, FDA, patients and their families, and Industry would be an important next step in clarifying opportunities and priorities to serve this vulnerable population.

Outcomes of Athletes With Genetic Heart Diseases and Implantable Cardioverter-Defibrillators Who Chose to Return to Play.

OBJECTIVE: To evaluate outcomes for athletes with a genetic heart disease (GHD) and an implantable cardioverter-defibrillator (ICD) after return-to-play (RTP) approval. PATIENTS AND METHODS: We conducted a retrospective review of athletes with GHD and an ICD who were evaluated and treated in Mayo Clinic's Genetic Heart Rhythm Clinic between July 2000 and July 2020. Data on frequency of GHD-associated breakthrough cardiac events (BCEs), inappropriate shocks, and ICD-related complications were collected and analyzed. RESULTS: There were 125 (57 [45.6%] female) GHD-positive athletes with an ICD (mean age at RTP was 19.8±11.6 years); 56 of 125 (44.8%) had long QT syndrome. Overall, 42 ventricular fibrillation-terminating ICD therapies were given to 23 athletes (18.4%) over an average follow-up of 3.6±3.5 years. Athletes with an ICD were more likely to experience a BCE during athletic follow-up (n=28 of 125, 22.4%) compared with those without an ICD (n=4 of 533, 0.8%; P<.0001). The BCE rate for athletes with ICDs was 6.3 events per 100 athlete-years of follow-up; this included 5.1 ventricular fibrillation-terminating events per 100 athlete-years compared with 0.3 BCEs per 100 patient-years for athletes without ICDs. In total, 6 (4.8%) athletes experienced at least one inappropriate shock (1.34 per 100 athlete-years) and 28 (29.6%) athletes had at least one other device-related complication (5.02 per 100 patient-years). However, none of these other complications occurred during sports. CONCLUSION: This 20-year single-center study provides the longest spanning retrospective review of outcomes for athletes with ICDs given RTP approval. For athletes with GHD and an ICD, no sports-associated deaths or reports of sports-related ICD damage occurred.

Cardiac Implantable Electronic Devices in Ebstein Anomaly: Management and Outcomes.

BACKGROUND: Optimal management of cardiac implantable electronic devices (CIEDs) in patients with Ebstein anomaly during tricuspid valve (TV) surgery is unknown. Thus, we aimed to characterize CIED management/outcomes in patients with Ebstein anomaly undergoing TV surgery. METHODS: Patients at the Mayo Clinic from 1987 to 2020 with Ebstein anomaly and CIED procedure were reviewed for procedural details, complications, echocardiogram, and lead parameters. Five-year cumulative incidence of CIED complications were estimated using the Kaplan-Meier method. RESULTS: Ninety-three patients were included; 51 were female, and mean age was 40.7±17.5 years. A new CIED was implanted in 45 patients at the time of TV surgery with the majority receiving an epicardial (n=37) CIED. Among 34 patients who had preexisting CIED (11 epicardial, 23 transvenous) at time of TV surgery, 20 had a transvenous right ventricular lead managed by externalizing the lead to the TV (n=15) or extracting the transvenous lead with epicardial lead implantation (n=5). Fourteen patients underwent CIED implantation (4 epicardial, 10 transvenous) without concurrent surgery. Placement of lead across the TV was avoided in 85% of patients. The 5-year cumulative incidence of CIED complications was 24% with no significant difference between epicardial and transvenous CIEDs (26% versus 23%, P=0.96). Performance of lead parameters was similar in epicardial and transvenous leads during median (interquartile range) follow-up of 44.5 (61.1) months. CONCLUSIONS: In patients with Ebstein anomaly undergoing TV surgery, the use of epicardial leads and externalization of transvenous leads to the TV can avoid lead placement across the valve leaflets. Lead performance and CIED complications was similar between epicardial and transvenous CIEDs.

Red herring pathogenic variants: a case report of premature ventricular contraction-triggered ventricular fibrillation with an incidental pathogenic LMNA variant.

Background: Pathogenic variants in the lamin A/C gene (LMNA) can lead to a wide range of phenotypes from dilated and arrhythmogenic cardiomyopathies and conduction abnormalities to partial lipodystrophies. This case highlights a coincidental pathogenic LMNA variant identified in a patient with sudden cardiac arrest (SCA). We demonstrate the need for careful interpretation of pathogenic variants identified in cardiomyopathy genes by highlighting a case in which a coincidental pathogenic LMNA variant was found in a patient with premature ventricular complex (PVC)-induced ventricular fibrillation (VF). Case summary: We present the case of a 16-year-old male with SCA secondary to VF. Genetic testing identified a maternally inherited pathogenic variant in LMNA annotated c.1961dup; p.T655Nfs*49. The patient received an implantable cardiac defibrillator and was discharged on nadolol. The patient's two brothers were also variant-positive. However, the patient and both brothers had normal chamber dimensions on echocardiogram and no late gadolinium enhancement on cardiac magnetic resonance imaging. The family members with the variant were recommended to have prophylactic implantable cardiac defibrillators and thus sought a second opinion. The patient received an appropriate shock and device interrogation identified PVCs. Electrophysiology study identified PVC-induced VF which was ablated with no recurrent ventricular arrhythmias/implantable cardioverter defibrillator therapies over 8 months of follow-up. Although the variant in LMNA could lead to cardiac arrest, the clinical phenotype was consistent with a non-genetic aetiology. The family members were told to have periodic cardiac evaluation. Discussion: This case demonstrates the identification of a coincidental pathogenic variant in a cardiomyopathy gene in a patient with cardiac arrest. Although this variant could lead to cardiomyopathy, it appears the cardiac arrest was not due to the pathogenic variant. This highlights the need to consider the clinical phenotype when interpreting genetic test results for cardiomyopathies even in the presence of a positive genetic test result.

From Safety to Benefit in Cell Delivery During Surgical Repair of Ebstein Anomaly: Initial Results.

BACKGROUND: The objective of this study is to assess the safety and early impact of intramyocardial delivery of autologous bone marrow-derived mononuclear cells (BM-MNC) at time of surgical Ebstein repair. METHODS: Patients with Ebstein anomaly (ages 6 months to 30 years) scheduled to undergo repair of the tricuspid valve were eligible to participate in this open-label, non-randomized phase I clinical trial. BM-MNC target dose was 1-3 million cells/kg. Ten patients have undergone surgical intervention and cell delivery to the right ventricle (RV) and completed 6-month follow-up. RESULTS: All patients underwent surgical tricuspid valve repair and uneventful BM-MNC delivery; there were no ventricular arrhythmias and no adverse events related to study product or delivery. Echocardiographic RV myocardial performance index improved and RV fractional area change showed an initial decline and then through study follow-up. There was no evidence of delayed myocardial enhancement or regional wall motion abnormalities at injection sites on 6-month follow-up magnetic resonance imaging. CONCLUSIONS: Intramyocardial delivery of BM-MNC after surgical repair in Ebstein anomaly can be performed safely. Echocardiography variables suggest a positive impact of cell delivery on the RV myocardium with improvements in both RV size and wall motion over time. Additional follow-up and comparison to control groups are required to better characterize the impact of cell therapy on the myopathic RV in Ebstein anomaly.

Role of chronic continuous intravenous lidocaine in the clinical management of patients with malignant type 3 long QT syndrome.

BACKGROUND: Type 3 long QT syndrome (LQT3) is caused by pathogenic, gain-of-function variants in SCN5A leading to a prolonged action potential, ventricular ectopy, and torsades de pointes. Treatment options include pharmacotherapy, cardiac denervation, and/or device therapy. Rarely, patients with malignant LQT3 require cardiac transplantation. OBJECTIVE: The purpose of this study was to evaluate the role of chronic continuous intravenous (IV) lidocaine as a therapeutic option for select patients with LQT3 refractory to standard therapy. METHODS: We performed a retrospective review of patients evaluated and treated at Mayo Clinic and identified 4 of 161 patients with LQT3 (2.5%) who were refractory to standard therapies and therefore treated with IV lidocaine. RESULTS: There were 4 patients (2 female [50%]). The median age at first IV lidocaine infusion was 2 months (interquartile range 1.5-4.8 months), and the median cumulative duration on IV lidocaine was 11.5 months (interquartile range 8.7-17.8 months). The main indication for IV lidocaine in all patients was persistent ventricular arrhythmias. Before IV lidocaine, all patients received an implantable cardioverter-defibrillator, and while on intermittent IV lidocaine, all patients underwent bilateral cardiac sympathetic denervation. Additionally, 2 (50%) patients had cardiac ablation for premature ventricular complexes. In all patients, lidocaine infusion resulted in a significant reduction of LQT3-triggered cardiac events. The main side effects of IV lidocaine observed were dizziness (n = 2, 50%) and seizures (n = 2, 50%). During follow-up, 3 of 4 (75%) patients underwent orthotopic cardiac transplantation. The remaining patient continues to receive IV lidocaine bolus for rescue as needed. CONCLUSION: For patients with LQT3 who are refractory to standard treatment, chronic IV lidocaine infusion can be used as a potential "bridge to transplant."

Surgical management of transvenous lead-induced tricuspid regurgitation in adult and pediatric patients with congenital heart disease.

OBJECTIVE: The objective of this study was to evaluate outcomes of surgical management of lead-induced tricuspid regurgitation (TR) in patients with congenital heart disease. METHODS: We analyzed data of 54 consecutive patients who underwent tricuspid valve (TV) surgery from 1998 to 2015 for lead-induced TR. Primary end points, including mortality, TV reinterventions, and longitudinal TR measurements, were analyzed with the Kaplan-Meier method or with repeated measures proportional odds modeling. RESULTS: The median age of patients was 48.2 years (interquartile range, 37.3-59.0 years); 31 (57.4%) were female; 2 (3.7%) were children. Thirty patients (55.6%) underwent TV repair and 24 (44.4%) had replacement, and 52 underwent concomitant cardiac procedures. Thirty-day mortality was 1.9% (repair: 3.3%, replacement: 0.0%). Five-year survival was 80.4% overall and 79.7% and 81.4% for the repair and replacement groups, respectively. In response to surgery, TR improved in both groups (each P < .001) but more with replacement than repair (P < .001); longitudinal analysis showed that TR trends observed early on favoring replacement were sustained across follow-up (P < .001). The model-estimated risk of moderate or severe TR at 5-year follow-up, conditional on having severe preoperative TR, was 74.4% for the repair and 10.7% for the replacement group. Five-year cumulative risk of TV reintervention was comparable for valve repair and replacement. CONCLUSIONS: Despite the need for concomitant cardiac procedures in most of the patients, early mortality was low after TV surgery. Survival and rate of TV reintervention were comparable for the repair and replacement groups. However, TV repair was associated with progressive TR during intermediate follow-up, especially in patients with severe preoperative TR.

Mejora progresiva de los umbrales de captura auricular y ventricular, detección e impedancias en los cables de estimulación epicárdica en adultos jóvenes que se someten a conversión de Fontan. / Progressive improvement of atrial and ventricular capture thresholds, sensing, and impedances in epicardial pacing leads in young adults undergoing Fontan conversion.

OBJECTIVES: Patients with univentricular hearts who require permanent pacing systems typically require placement of epicardial leads. It is frequently difficult to find a position with good thresholds due to epimyocardial fibrosis or fat. The goal of the study is to assess the progression of capture thresholds (CT), sensing parameters (P waves and R waves), and impedances (imp) of steroid eluting epicardial pacing leads in young adults who underwent Fontan conversion and a pacemaker implant. METHODS: All patients undergoing Fontan conversion in two institutions were retrospectively identified. Demographic data, congenital heart defects, pacing leads used, and pacing parameters were analyzed at implant, at 6 weeks and 12 months after implant. RESULTS: Twenty patients were identified (twelve males); mean age at conversion was 24.9 ± 5.4 years (range 18-35). Epicardial bipolar steroid eluting leads were used. The site of implant both in the atria and the ventricles varied depending on the parameters. At implant, mean atrial and ventricular impedances were 617 ± 171 Ω and 1061 ± 771 Ω, respectively, mean P wave amplitude was 2 ± 0.7 mV, and mean R wave amplitude was 12.5 ± 7.7 mV. Mean CT was 1.7 ± 0.8 V at 0.5 ms for the atrium and 2.2 ± 1.2 V at 0.5 ms for the ventricle. Ventricular CT and impedance showed an improvement within the first 12 months after implant, with four patients having a decrease in threshold of more than 2 V. CONCLUSION: In patients undergoing Fontan conversion, implant ventricular CT and impedances are frequently higher than expected but typically improve during follow-up. Acceptance of higher initial threshold values may be a potential strategy in this patient population.

OBJETIVO: Los pacientes con corazón univentricular que requieren estimulación cardíaca reciben sistemas de estimulación epicárdicos. Debido a la presencia de fibrosis o grasa epi-miocárdica es dificultoso en esta población encontrar sitios con adecuados parámetros de estimulación. El objetivo de este estudio es determinar la progresión de los umbrales de captura, los parámetros de sensado (medición de las ondas P y R) e impedancias (imp) de los catéteres epicárdicos con liberación de esteroides implantados en adultos jóvenes sometidos a cirugía de reconversión de Fontan e implante de marcapasos. MÉTODOS: Los pacientes sometidos a cirugía de reconversión de Fontan en dos instituciones fueron analizados retrospectivamente. Los datos demográficos, el tipo de cardiopatía congénita, de catéteres de estimulación y los parámetros de estimulación fueron analizados al momento del implante, a las 6 semanas y al año. RESULTADOS: Se identificaron 20 pacientes (12 de ellos de sexo masculino); la edad media al momento de la reconversión fue de 24.9 ± 5.4 años (rango 18-35). Se utilizaron catéteres epicárdicos bipolares de fijación pasiva y con liberación de esteroides en todos los casos. El sitio de implante en las aurículas y en los ventrículos fue variable de acuerdo a los parámetros. En el momento del implante las impedancias medias fueron 617 ± 171 W y 1061 ± 771 W respectivamente, la amplitud media de la onda P fue 2 ± 0.7 mV y la media de amplitud de la onda R fue de 12.5 ± 7.7 mV. Las medias de los umbrales de captura fueron 1.7 ± 0.8 V at 0.5 ms para los catéteres auriculares y 2.2 ± 1.2 V at 0.5 ms para los ventriculares. Los umbrales de captura y las impedancias ventriculares mostraron una mejoría en los 12 meses posteriores al implante, y en 4 pacientes esa mejoría en el umbral de captura ventricular fue mayor a 2 V. CONCLUSIONES: En pacientes sometidos a una cirugía de reconversión de Fontan e implante de marcapasos, los umbrales de captura e impedancias ventriculares son más elevados que los esperados, pero mejoran durante el seguimiento. La aceptación de valores más elevados puede potencialmente constituir una alternativa en esta población de pacientes.

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.

Comparative outcomes of subcutaneous and transvenous cardioverter-defibrillators.

BACKGROUND: The comparative outcomes of subcutaneous implantable cardioverter-defibrillator (S-ICD) and transvenous ICD (T-ICD) have not been well studied. The aim of this study was to evaluate the safety and efficacy of currently available S-ICD and T-ICD. METHODS: The study included 86 patients who received an S-ICD and 1:1 matched to those who received single-chamber T-ICD by gender, age, diagnosis, left ventricular ejection fraction (LVEF), and implant year. The clinical outcomes and implant complications were compared between the two groups. RESULTS: The mean age of the 172 patients was 45 years, and 129 (75%) were male. The most common cardiac condition was hypertrophic cardiomyopathy (HCM, 37.8%). The mean LVEF was 50%. At a mean follow-up of 23 months, the appropriate and inappropriate ICD therapy rate were 1.2% vs. 4.7% (χ = 1.854, P = 0.368) and 9.3% vs. 3.5% (χ = 2.428, P = 0.211) in S-ICD and T-ICD groups respectively. There were no significant differences in device-related major and minor complications between the two groups (7.0% vs. 3.5%, χ = 1.055, P = 0.496). The S-ICD group had higher T-wave oversensing than T-ICD group (9.3% vs. 0%, χ = 8.390, P = 0.007). Sixty-five patients had HCM (32 in S-ICD and 33 in T-ICD). The incidence of major complications was not significantly different between the two groups. CONCLUSIONS: The efficacy of an S-ICD is comparable to that of T-ICD, especially in a dominantly HCM patient population. The S-ICD is associated with fewer major complications demanding reoperation.

Supraventricular tachycardias, conduction disease, and cardiomyopathy in 3 families with the same rare variant in TNNI3K (p.Glu768Lys).

BACKGROUND: Rare genetic variants in TNNI3K encoding troponin-I interacting kinase have been linked to a distinct syndrome consisting primarily of supraventricular tachycardias and variably expressed conduction disturbance and dilated cardiomyopathy in 2 families. OBJECTIVE: The purpose of this study was to identify new genetic variants associated with inherited supraventricular tachycardias, cardiac conduction disease, and cardiomyopathy. METHODS: We conducted next generation sequencing in 3 independent multigenerational families with atrial/junctional tachycardia with or without conduction disturbance, dilated cardiomyopathy, and sudden death. We also assessed the effect of identified variant on protein autophosphorylation. RESULTS: In this study, we uncovered the same ultra-rare genetic variant in TNNI3K (c.2302G>A, p.Glu768Lys), which co-segregated with disease features in all affected individuals (n = 23) from all 3 families. TNNI3K harboring the TNNI3K-p.Glu768Lys variant displayed enhanced kinase activity, in line with expectations from previous mouse studies that demonstrated increased conduction indices and procardiomyopathic effects with increased levels of Tnni3k. CONCLUSION: This study corroborates further the causal link between rare genetic variation in TNNI3K and this distinct complex phenotype, and points to enhanced kinase activity of TNNI3K as the underlying pathobiological mechanism.