Showing papers by "Gan-Xin Yan published in 2003"

Effect of Epicardial or Biventricular Pacing to Prolong QT Interval and Increase Transmural Dispersion of Repolarization Does Resynchronization Therapy Pose a Risk for Patients Predisposed to Long QT or Torsade de Pointes

Abstract: Background— The present study examined pacing site–dependent changes in QT interval and transmural dispersion of repolarization (TDR) and their potential role in the development of torsade de pointes (TdP). Methods and Results— In humans, the QT interval, JT interval, and TDR were measured in 29 patients with heart failure during right ventricular endocardial pacing (RVEndoP), biventricular pacing (BiVP), and left ventricular epicardial pacing (LVEpiP). In animal experiments, pacing site–dependent changes in ventricular repolarization were examined with a rabbit left ventricular wedge preparation in which action potentials from endocardium and epicardium could be simultaneously recorded with a transmural ECG. In humans, LVEpiP and BiVP led to significant QT and JT prolongation. LVEpiP also enhanced TDR. Frequent R-on-T extrasystoles generated by BiVP and LVEpiP but completely inhibited by RVEndoP occurred in 4 patients, of whom 1 developed multiple episodes of nonsustained polymorphic ventricular tachycardia and another suffered incessant TdP. In rabbit experiments, switching from endocardial to epicardial pacing produced a net increase in QT interval and TDR by 17±5 and 22±5 ms, respectively (n=6, P Conclusions— LVEpiP and BiVP increase QT, JT, and TDR by altering the transmural sequence of activation of the intrinsically heterogeneous ventricular myocardium. Our data suggest that the resultant exaggeration of arrhythmic substrates can lead to the development of TdP in a subset of patients.

Electrocardiographic T wave: a symbol of transmural dispersion of repolarization in the ventricles.

Abstract: Surface ECG waveforms are known to depend on the properties of transmembrane action potentials of cardiomyocytes, the spread of excitation, and the characteristics of the volume conductor, among which the transmembrane action potential is the generator of these waveforms. In other words, any wave on the surface ECG is a manifestation of a potential gradient due to cellular electrical activity within the heart. Obviously, the ECG T wave represents such a potential gradient during ventricular repolarization. The genesis of an upright T wave has been a matter of debate dating back many decades.1,2 An apico-basal voltage gradient, due to a difference in action potential duration (APD) between apical and basal regions, initially was proposed to be responsible for the ECG T wave.1 However, a recent study has demonstrated that the apico-basal voltage gradient contributes little to the T wave on the ECG.3 On the other hand, the concordance of polarity between QRS and T waves, particularly in left precordial leads, suggests that normal ventricular electrical recovery, in contrast to ventricular activation, is from epicardium to endocardium, i.e., a process that generates a transmural voltage gradient.2,4 In the early 1980s, Higuchi and Nakaya4 demonstrated that cooling of canine ventricular epicardial surface, which resulted in prolongation of APD in the epicardium, produced a negative T wave. In contrast, warming of the epicardium, which was associated with APD shortening in the epicardium, led to an upright T wave. They concluded that APD at least 40 to 60 msec longer in the endocardium than in the epicardium was required for the upright T wave.4 However, ionic and cellular basis for the genesis of the positive T wave was not established until the 1990s, when a new subpopulation of cells within ventricular myocardium, i.e., M cells, was discovered by Antzelevitch and colleagues.5 It now is generally accepted that ventricular myocardium is not uniform but rather is composed of at least three electrophysiologically distinct cell types: epicardium, M cells residing at the deep subendocardial layer, and endocardium.5,6 Epicardial, endocardial, and M cells differ primarily from each other by their repolarization properties. The hallmark of M cells is their tendency to have their action potentials prolonged disproportionately to epicardium or endocardium in response to slowing of pacing rate or to drugs that prolong the action potential.3,7-9 The delayed repolarization of M cells and its influence on epicardium and endocardium via

Electrophysiologic effects of SB-237376: a new antiarrhythmic compound with dual potassium and calcium channel blocking action.

Abstract: Combined potassium and calcium channel blocking activities are suggested to be the basis for antiarrhythmic efficacy with low proarrhythmic risk. The electrophysiologic effects of SB-237376 were investigated in single myocytes and arterially perfused wedge preparations of canine or rabbit left ventricles. The concentration-dependent prolongation of action potential duration (APD) and QT interval by SB-237376 was bell-shaped and the maximum response occurred at 1-3 microM SB-237376 inhibited rapidly activating delayed rectifier K current (I(Kr) ) with an IC50 of 0.42 microM and use-dependently blocked L-type Ca current (I (Ca,L) ) at high concentrations. The SB-237376 (3 microM) induced phase-2 early afterdepolarizations (EADs) in five of six rabbit wedge preparations but none of six canine wedge preparations. This is probably due to larger increases of APD, QT interval, and transmural dispersion of repolarization (TDR) in rabbits than dogs. Based on the drug effects on QT interval, TDR, and EAD in rabbit ventricular wedge preparations, a scoring system predicted lower proarrhythmic risk for SB-237376 than for dl-sotalol, a specific I blocker. In conclusion, SB-237376 increases APD, QT interval, and TDR mainly by I (Kr) inhibition. These effects are self-limited due to SB-237376-induced I(Ca,L) blockade at high concentrations, which may explain its lower proarrhythmic risk than dl-sotalol.

Pharmacologic and nonpharmacologic options to maintain sinus rhythm: guideline-based and new approaches.

Abstract: Atrial fibrillation is a common arrhythmia in patients with heart failure and is responsible for substantial morbidity and mortality. Restoration and preservation of sinus rhythm, therefore, has a premium. Of the numerous treatment options available, many must be avoided because of their potential for adverse effects or because of limited proof of efficacy in defined populations. Published guidelines provide help by synthesizing clinical trial data into a recommended approach. This article summarizes current information regarding the best methods applicable to patients with left ventricular dysfunction for rate control, sinus rhythm restoration and maintenance, and stroke prevention. New and evolving therapies and how they might fit into the evolving treatment paradigm are also briefly reviewed.

Overview of the management of atrial fibrillation: what is the current state of the art?

Abstract: Management of Atrial Fibrillation. There are three fundamental approaches to the management of atrial fibrillation (AF): rate control, rhythm control, and anticoagulation. Selecting a course of treatment requires a thorough knowledge of these therapeutic alternatives. This article explores treatment options, including the relative benefits of rate control versus rhythm control, which are complicated by the lack of highly effective and safe antiarrhythmic drugs. Anticoagulation is also an important issue in AF management, and warfarin effectively reduces the incidence of thromboembolic events in AF patients. The use of warfarin, however, presents its own complications. We conclude that individualization of therapy is paramount when treating AF.