The objective was to determine the role of ATP1A3 genetic variants on cardiac outcomes as determined by QT and corrected QT (QTc) measurements. Although these patients experience a high rate of sudden unexpected death in epilepsy, the pathophysiologic basis for this risk remains unknown.
Pathogenic variation in the ATP1A3 ‐encoded sodium‐potassium ATPase, ATP1A3, is responsible for alternating hemiplegia of childhood (AHC). 2,31 Studies focusing on the D801N variant show through homology modeling that the D801N variant creates a positive dipole which consequently affects the flow of potassium through the pump via electrostatic repulsion 41 and reduced sodium-potassium ATPase activity and pump current in mammalian cells. 30,31, Although ATP1A3-D801N is associated with a mild-moderate form of AHC from a neurological perspective, 21,40 it has been implicated in more severe cardiac phenotypes. Previous work in principally neuronal models has revealed that differing protein variants in the alpha-3 subunit of the ATP1A3 gene that result in the syndrome of cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss rapid-onset dystonia parkinsonism and AHC cause specific disruptions that cause reduced affinity at the cytoplasmic surface, widely distributed protein dysfunction, or dysfunction at the cytoplasmic surface in the transmembrane domain, respectively. Kumar and Clark Clinical Medicine 4th Edition, W.B SAUNDERS 1998. Hurst’s The Heart 8th Edition, McGRAW-HILL 1994. Intraventricular Conduction Blocks References The underlying cause of a bundle branch block should always be treated- the conduction defecit may resolve. More severe arrhythmias may require permanent pacing. Mild partial bundle branch blocks require no treatment. How is Intraventricular Conduction Blocks Treated? Treatment such as insertion of a pacemaker is available if complete heart block becomes imminent. The prognosis of bundle branch blocks depends on what caused the disorder, and whether the conduction disturbs progress. Prognosis of Intraventricular Conduction Blocks Cardiac enzymes may be elevated if the bundle branch block is secondary to an acute myocardial infarction, but only if this is an acute event. A chest x-ray will show any obvious ventricular disease such as hypertrophy or cardiomyopathies – Blood Tests should exclude electrolyte imbalances as a cause of bundle branch block. How is Intraventricular Conduction Blocks Diagnosed? The importance of bundle branch blocks is that they can indicate conduction disease of the heart, and they may progress to complete heart block. For instance right bundle branch block results in delayed right ventricular contraction and left bundle branch block causes delayed left ventricular contraction. Progression of Intraventricular Conduction BlocksĪ block of either branch of the ventricular conducting system produces a de-coordination of the contraction of the two ventricles (the left and the right). Risk Factors for Intraventricular Conduction BlocksĬauses of a right bundle branch block include:Ĭauses of a left bundle branch block include myocardial disease, particularly myocardial infarction, left ventricular outflow obstructions and fibrosis of the conducting system.