ATP1A3-Encoded Sodium-Potassium ATPase Subunit Alpha 3 D801N Variant Is Associated With Shortened QT Interval and Predisposition to Ventricular Fibrillation Preceded by Bradycardia.

Background Pathogenic variation in the ATP1A3-encoded sodium-potassium ATPase, ATP1A3, is responsible for alternating hemiplegia of childhood (AHC). Although these patients experience a high rate of sudden unexpected death in epilepsy, the pathophysiologic basis for this risk remains unknown. The objective was to determine the role of ATP1A3 genetic variants on cardiac outcomes as determined by QT and corrected QT (QTc) measurements. Methods and Results We analyzed 12-lead ECG recordings from 62 patients (male subjects=31, female subjects=31) referred for AHC evaluation. Patients were grouped according to AHC presentation (typical versus atypical), ATP1A3 variant status (positive versus negative), and ATP1A3 variant (D801N versus other variants). Manual remeasurements of QT intervals and QTc calculations were performed by 2 pediatric electrophysiologists. QTc measurements were significantly shorter in patients with positive ATP1A3 variant status (P<0.001) than in patients with genotype-negative status, and significantly shorter in patients with the ATP1A3-D801N variant than patients with other variants (P<0.001). The mean QTc for ATP1A3-D801N was 344.9 milliseconds, which varied little with age, and remained <370 milliseconds throughout adulthood. ATP1A3 genotype status was significantly associated with shortened QTc by multivariant regression analysis. Two patients with the ATP1A3-D801N variant experienced ventricular fibrillation, resulting in death in 1 patient. Rare variants in ATP1A3 were identified in a large cohort of genotype-negative patients referred for arrhythmia and sudden unexplained death. Conclusions Patients with AHC who carry the ATP1A3-D801N variant have significantly shorter QTc intervals and an increased likelihood of experiencing bradycardia associated with life-threatening arrhythmias. ATP1A3 variants may represent an independent cause of sudden unexplained death. Patients with AHC should be evaluated to identify risk of sudden death.

Salvage of an epicardial lead in a pacemaker-dependent patient with Fontan palliation using an IS-1 extender.

We present a case report of severed epicardial atrial lead salvage using an IS-1 lead extender. A 37-year-old male with single ventricle physiology, Fontan palliation, sinus node dysfunction, recurrent atrial tachycardias, and atrial fibrillation resulting in failing Fontan physiology presented with failure of the atrial pacing lead. The patient was initially paced with an epicardial system that had to be removed due to pocket infection, and the epicardial leads were cut and abandoned. Given his significant sinus node dysfunction he required atrial pacing to allow for rhythm control. The failing Fontan physiology of the patient precluded him from undergoing surgery for epicardial lead placement or a complex intravascular lead placement procedure (although anatomically feasible). We considered the option of salvaging the existing epicardial atrial leads to provide atrial pacing, allowing for rhythm control and improvement of his failing Fontan physiology as a bridge to a more permanent pacing solution. This case report is important because it demonstrates how a lead extender can be used to salvage a severed pacemaker lead. This may be useful for patients in whom implantation of new leads is not promptly feasible due to patient anatomy and/or clinical status.

Late outcomes in children with Shone's complex: a single-centre, 20-year experience.

OBJECTIVE: Shone's syndrome is a complex consisting of mitral valve stenosis in addition to left ventricle outflow obstruction. There are a few studies evaluating the long-term outcomes in this population. We sought to determine the long-term outcomes in our paediatric population with Shone's syndrome and the factors associated with left heart growth. METHODS: All patients diagnosed with Shone's syndrome with biventricular circulation treated between 1978 and 2010 were reviewed. Baseline echocardiograms and data from catheterisations were also reviewed. Number of interventions (surgical+transcatheter), incidence of mitral valve replacement, and incidence of heart transplantation were tracked. Survival of the population and left heart structural growth were also reviewed. RESULTS: A total of 121 patients with Shone's syndrome presented at a median age of 28 days (0-17.3 years) and were followed-up for 7.2 years (0.01-35.5 years). These patients underwent 258 interventions during the study period, and the presence of coarctation was associated with repeat left heart interventions. The 10-year, transplant-free survival was 86%. Presence of pulmonary hypertension was associated with mortality. Left heart structural growth was seen for mitral and aortic valve annuli and left ventricular end-diastolic dimension over time. CONCLUSIONS: Shone's syndrome patients undergo a number of left heart interventions. Coarctation of the aorta is associated with an increased likelihood for repeat interventions. Survival appears to be more favourable than expected. Significant left heart growth will occur in the population. Pulmonary hypertension is associated with an increased risk of mortality.

Follow-Up of Electrocardiographic Findings and Arrhythmias in Patients With Anomalously Arising Left Coronary Artery from the Pulmonary Trunk.

Follow-up data and correlation of arrhythmias, electrocardiogram (ECG) changes, and cardiac function in anomalous left coronary artery from the pulmonary trunk or artery have not been previously studied. This is a retrospective single-center review of 44 anomalous left coronary artery from the pulmonary trunk or artery patients diagnosed between 1992 and 2014, at a median age of 3 months (3 days to 13 years). Clinical history, ECG, Holter, and echocardiogram data were reviewed. ECGs were reviewed for contiguous Q-or T-wave inversions, hypertrophy, bundle branch block, and axis deviation. High-grade ventricular ectopy, supraventricular tachycardia (SVT), and ventricular tachycardia (VT) were recorded. Patients with <6 months of clinical follow-up were excluded from longitudinal analysis. At diagnosis, 43 (98%) were noted to have electrocardiographic changes. During hospitalization, arrhythmias were seen in 13 patients (30%): 2 (5%) with sustained VT or ventricular fibrillation, 6 (17%) with high-grade ventricular ectopy, and 4 (9%) with SVT. Seven patients (16%) required antiarrhythmic treatment. During outpatient follow-up, arrhythmias were seen in 11 patients. New arrhythmias were documented in 6 without a history of in-hospital arrhythmias. Of 34 patients with at least 6 months follow-up (median 6 years, 0.5 to 20 years), 20 had left ventricular (LV) dysfunction before surgery. Normalization of function occurred in 94% (median 1 year, 5 days to 4 years). Electrocardiographic changes persisted in 94% at the time of LV function recovery. In conclusion, electrocardiographic changes and arrhythmias may persist despite recovery of ventricular function. Therefore, prolonged myocardial remodeling may continue even after resolution of LV dysfunction during which time arrhythmias may occur.