Using a new method for long-term recording of monophasic action potentials from the human heart, we studied in 17 patients the effects on ventricular action potential duration (APD) of three clinically pertinent cycle length perturbations:(1) single extrastimuli, (2) abrupt sustained rate acceleration and deceleration, and (3) different steady-state cycle lengths. Results were: (a) APD after single extrastimuli at progressively longer cycle lengths were related to the extrastimulus cycle length with a biphasic electrical restitution curve which after an initial steep rise and a subsequent transient descent rose again more gradually to a plateau at cycle lengths above 800-1,000 ms. (b) After a sustained step decrease in cycle length, the first APD shortened abruptly while final steadystate adaptation required up to several minutes. The transition between the rapid and slow phase of APD change was characterized by a variable alternans of APD which correlated inversely with the preceding diastolic interval. (c) In the steady state, APD correlated linearly with cycle length, increasing an average of 23 ms per 100 ms cycle length increase (r = 0.995). The divergence between steady-state and non-steady-state APD, and the slowness of steady-state adaptation, are important factors to be considered in clinical electrophysiologic studies and in rate correction algorithms of APD or QT intervals, respectively.

The scientific and clinical basis of drug-induced QT prolongation and proarrhythmia was summarized by formal presentations. The speakers were chosen for their particular competence in the relevant field. Furthermore, selected topics were discussed in detail in separate workshops. This document represents the executive summary of the Conference. It is based on written reports composed by the speakers and the chairs of the workshops. Before preparation of the final version of the document, a draft was circulated to all participants of the Conference for suggestions and comments. The opinions expressed in this document are those of the participants and do not necessarily reflect the official position of their organisations or agencies. The meeting was made possible by unrestricted educational grants to the Committee for Scientific and Clinical Initiatives of the ESC from several companies listed in the Appendix. The problemQT interval prolongation, and possibly increased QT dispersion, are risk factors in a number of cardiovascular as well as non-cardiovascular diseases. A variety of drugs prolong the QT interval, although the major examples are the so-called class III antiarrhythmics. These drugs generally exert their therapeutic effect by affecting potassium ion channels, thereby reducing outward, repolarizing current, and prolonging action potential duration and the QT interval. Many of these drugs have been developed for conversion of atrial fibrillation and/or maintenance of sinus rhythm in patients with recurrent atrial fibrillation. Such patients are at low risk of potentially fatal arrhythmias, at least in the absence of antiarrhythmic drug therapy.However, antiarrhythmic drugs which prolong cardiac repolarization are not harmless, as they may induce

Background The substrates for human atrial fibrillation (AF) are poorly understood but involve abnormal repolarization (action potential duration, APD). We hypothesized that beat-to-beat oscillations in APD may explain AF substrates and why vulnerability to AF forms a spectrum from control subjects without AF to patients with paroxysmal then persistent AF. Methods and Results In 33 subjects (12 persistent AF, 13 paroxysmal AF, 8 controls without AF), we recorded left (n=33) and right (n=6) atrial APD on pacing from cycle lengths (CL) 600–500 ms (100–120 beats/min) to AF. APD alternans required progressively faster rates for patients with persistent AF, paroxysmal AF and controls (CL 411±94 vs 372±72 vs 218±33 ms; p<0.01). In AF patients, APD alternans occurred at rates as slow as 100–120 beats/min, unrelated to APD restitution (p=NS). In this milieu, spontaneous ectopy initiated AF. At fast rates, APD alternans disorganized to complex oscillations en route to AF. Complex oscillations also arose at progressively faster rates for persistent AF, paroxysmal AF and controls (CL: 316±99 vs 266±19 vs 177±16 ms; p=0.02). In paroxysmal AF, APD oscillations amplified prior to AF (p<0.001). In controls, APD alternans arose only at very fast rates (CL < 250 ms; p<0.001 vs AF groups) just prior to AF. In n=4 AF patients in whom rapid pacing did not initiate AF, APD alternans arose transiently then extinguished. Conclusions Atrial APD alternans reveals dynamic substrates for AF, arising most readily (at lower rates and higher magnitudes) in persistent AF then paroxysmal AF, and least readily in controls. APD alternans preceded all AF episodes, and was absent when AF did not initiate. The cellular mechanisms for APD alternans near resting heart rates require definition.

No abstract

Membrane depolarization is caused by both gradual and rapid ventricular stretch, but PVEs are more easily elicited by rapid stretch. Regions of greater myocardial compliance that experience greater relative stretch may act as "foci" for stretch-activated arrhythmias during dynamic ventricular loading. These whole-heart data corroborate the existence of stretch-activated membrane channels in ventricular myocardium and may help explain ventricular ectopy under conditions of differential ventricular loading, as in ventricular dyskinesia, or regional muscle traction, as in mitral valve prolapse syndrome.

Computerized T-wave morphology analysis of the 12-lead resting ECG permits independent assessment of post-MI risk and an improved risk stratification when combined with other risk markers.

The JT and QT dispersion correlate significantly with dispersion of APD90 and recovery time. The ECG assessment of dispersion of repolarization can be improved by three new ECG dispersion indexes: T peak to T end interval, total T wave area and late T wave area. These new indexes should be tested clinically.

No abstract