Altered Dynamics of Action Potential Restitution and Alternans in Humans With Structural Heart Disease

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Abstract
Background— Restitution kinetics and alternans of ventricular action potential duration (APD) have been shown to be important determinants of cardiac electrical stability. In this study, we tested the hypothesis that APD restitution and alternans properties differ between normal and diseased human ventricular myocardium. Methods and Results— Monophasic action potentials were recorded from the right ventricular septum in 24 patients with structural heart disease (SHD) and in 12 patients without SHD. Standard and dynamic restitution relations were constructed by plotting APD as a function of the preceding diastolic interval. The dynamic restitution relation of both groups showed a steeply sloped segment at short diastolic intervals that was associated with the occurrence of APD alternans. Patients with SHD had a wider diastolic interval range over which APD alternans was present (mean±SEM 68±11 versus 12±2 ms) and showed an earlier onset (168±7 versus 225±4 bpm) and an increased magnitude (20±2 versus 11±2 ms) of APD alternans compared with patients without SHD. The occurrence of APD alternans during induced ventricular tachycardia (6 episodes) and during rapid pacing could be derived from the dynamic restitution function. Conclusions— There are marked differences in the dynamics of APD restitution and alternans in the ventricular myocardium of patients with SHD compared with patients without SHD. These differences may contribute importantly to cardiac electrical instability in diseased human hearts and may represent a promising target for antiarrhythmic substrate modification.