Faculty Bibliography

BACKGROUND:Atrial standstill is an arrhythmogenic condition characterized by the absence of spontaneous electrical and mechanical atrial activity or in response to stimulation. There are few reported familial cases which have been associated with SCN5A mutations co-segregating with GJA5 or RYR2 however isolated SCN5A mutations are rare. OBJECTIVE:The purpose of this study was to determine the clinical and biophysical consequence of a novel SCN5A mutation identified in a family with progressive atrial standstill and sudden death. METHODS:The family of a sporadic case of congenital atrial standstill underwent genetic screening. Human Embryonic Kidney 293 cells were transfected with wild-type (WT) or mutant SCN5A cDNAs. Biophysical properties were studied using whole-cell using patch clamp methods. RESULTS:A novel homozygous SCN5A mutation, p.V1340L was identified in the proband and her sister. The proband had complete atrial standstill whereas the sister had partial atrial standstill. Heterozygous mutations were identified in the mother, father and brother. All three had normal sinus rhythm and were asymptomatic. The mutant Nav1.5(V1340L) reduced Nav1.5 current density as well as showed a depolarizing shift in the voltage-dependent steady-state activation (WT: -35.3±1.62 mV; V1340L: -22.4±2.59 mV; P = 0.001). CONCLUSIONS:A homozygous loss-of-function SCN5A mutation likely results in atrial standstill and sudden death due to suppression of initiation of action potential.

BACKGROUND: Experience with percutaneous epicardial ablation of tachyarrhythmia in pediatrics is limited. This case series addresses the feasibility, safety and complications of the procedure in children. METHODS: A total of 9 patients underwent 10 epicardial ablation procedures from 2002 to 2013 at two academic centers. Activation mapping was performed in all cases, and electro-anatomic map was utilized in 9 of the 10 procedures. Patients had undergone 1-3 failed endocardial catheter ablations in addition to medical management, and all had symptoms, a high-risk accessory pathway (AP), aborted cardiac arrest with Wolff-Parkinson-White syndrome (WPW) or ventricular dysfunction. A standard epicardial approach was used for access in all cases, using a 7 or 8 Fr sheath. Epicardial ablation modality was radiofrequency (RF) in 7, cryoablation (CRYO) in 1, and CRYO plus RF in 1. RESULTS: Median age was 14 (range 8-19) yrs. INDICATIONS: drug refractory ectopic atrial tachycardia - 1, ventricular tachycardia (VT) - 5, high-risk

Implanting cardiac rhythm medical devices in adults with congenital heart disease requires training in congenital heart disease. The techniques and indications for device implantation are specific to the anatomic diagnosis and state of disease progression. It often requires a team of physicians and is best performed at a specialized adult congenital heart center.

Hypertrophic cardiomyopathy (HCM) is a variable disease both phenotypically and genetically with challenges surrounding identification of those individuals at risk of sudden death. Current guidelines by the American Heart Association (AHA)/American College of Cardiology (ACC) recommend clinical screening of children with first-degree family members with HCM starting at the age of 12 or the onset of puberty.We report a case of a child with known double-heterozygous mutations causative of HCM. The child had evidence of HCM by 4. months of age, and experienced aborted cardiac death starting at 7. years of age. This case suggests that multiple HCM-associated genetic mutations may portend a higher risk for severe HCM and predispose to early onset cardiac arrest, thereby requiring earlier clinical screening.

BACKGROUND: -The ability to identify and ablate different arrhythmia mechanisms following the total cavopulmonary connection (TCPC) has not been studied in detail. METHODS AND RESULTS: -After obtaining IRB approval according to institutional guidelines, consecutive patients following a TCPC undergoing electrophysiology study over a 6 year period were included (2006-2012). Arrhythmia mechanism was determined, and the procedural outcome was defined as complete, partial success, or failure. A 12-point arrhythmia severity score was calculated for each patient at baseline and on follow-up. Fifty-seven procedures were performed on 52 patients (18.4 +/- 11.8 years; 53.0 +/- 27.2kg). Access to the pulmonary venous atrium was necessary in 33 procedures, via fenestration (16) or transbaffle puncture (17) and in two cases an additional retrograde approach was used. In total, 80 arrhythmias were identified in 47 cases: macroreentrant (n=25) or focal atrial tachycardia (n=8), atrioventricular nodal reentry tachycardia (n=13), reentry via an accessory pathway (n=4) or via twin atrioventricular nodes (n=4), ventricular tachycardia (n=5), and undefined atrial tachycardia (n=21). Procedural outcome in 32 patients who underwent ablation was complete success (n=25), partial success (n=3), failure (n=3), or empiric ablation (n=1). Following successful ablation there was a significant decrease in arrhythmia score over 18.2 (4 - 32) months follow-up, with a sustained trend even in the face of arrhythmia recurrence (50%). CONCLUSIONS: -Arrhythmia mechanism post TCPC is highly varied, encompassing simple and more complex substrates, documentation of which facilitates a strategic approach to invasive arrhythmia management. Despite the anatomical limitations successful and clinically meaningful ablation is possible.