Abstract 10368: Early Afterdepolarization Alternans Manifests T Wave Alternans in Left Ventricular Hypertrophy
Objectives: T wave alternans (TWA) in the setting of left ventricular hypertrophy (LVH) and failure often heralds the development of R-on-T ectopic beat and torsade de pointes. In humans with LVH, the R-on-T ectopic always occurs on the broad abnormal T wave with a long QT interval during TWA (Figure). Early afterdepolarization (EAD) alternans may contribute to TWA on the ECG, however, direct evidence is lacking. In this study, we examined cellular and ion mechanisms for EAD and its role in TWA in LVH.
Methods & Results: The renovascular hypertension model was used to induce LVH in rabbits. In the left ventricular wedge preparations, TWA occurred spontaneously in 8 of 31 LVH rabbits vs. 0 of 26 in controls at slow pacing rates of 0.25 or 0.5 Hz (p<0.01). EAD alternans in endocardial action potential was responsible for the broad abnormal T wave with a long QT interval on the ECG during TWA (Figure). EAD from the endocardium induced a new action potential in the epicardium via phase 2 reentry that manifested an R-on-T ectopic beat on the ECG. LVH produced a significant increase in late sodium current (INa-L) in the endocardium but not epicardium. Further increase in INa-L by ATX-II at 1 nM facilitated the development of EAD alternans and resultant TWA. In contrast, ranolazine (INa-L inhibitor) at 10 to 30 μM suppressed EAD and abolished spontaneous as well as ATX-II induced TWA in LVH rabbits.
Conclusions: We provide direct evidence that endocardial EAD alternans is responsible for TWA in LVH. An increase in INa-L plays an important role in the development of EAD alternans in the endocardium.Ranolazine may have a unique benefit in the treatment of arrhythmias associated with LVH.
- © 2013 by American Heart Association, Inc.