Time- and rate-dependent alterations of the QT interval precede the onset of torsade de pointes in patients with acquired QT prolongation.

OBJECTIVES The purpose of this study was to determine whether the QT interval dynamics that precede torsade de pointes are consistent with the initiation of this arrhythmia by early afterdepolarization-induced triggered activity. BACKGROUND Early afterdepolarization-induced triggered activity has been suggested as an electrophysiologic mechanism for torsade de pointes. Consequently, the initiation of torsade de pointes should involve time- and rate-dependent alterations of ventricular repolarization similar to those known to modulate the development of early afterdepolarizations. METHODS RR and QT intervals were measured in digitized 24-h ambulatory electrocardiographic recordings obtained from seven patients with acquired prolongation of ventricular repolarization. Each patient had one or more episodes of torsade de pointes. The relation between RR and QT intervals was determined before, during and after multiple episodes of torsade de pointes. RESULTS In patients with multiple episodes of ventricular arrhythmias, the onset of the arrhythmias was associated with a critical prolongation of the QT interval. In some episodes, prolongation of the QT interval was associated with sudden prolongation of the sinus cycle length, whereas in other episodes, the QT interval prolonged progressively at a constant cycle length. CONCLUSIONS The association between a critically prolonged QT interval and the onset of ventricular arrhythmias suggests that the initial complex of torsade de pointes is an early afterdepolarization-induced triggered response. However, prolongation of the QT interval itself was not sufficient to account for the initiation of torsade de pointes, suggesting that other, as yet unidentified factors are required.

[1]  B. Surawicz Electrophysiologic substrate of torsade de pointes: dispersion of repolarization or early afterdepolarizations? , 1989, Journal of the American College of Cardiology.

[2]  B F Hoffman,et al.  Action Potential Prolongation and Induction of Abnormal Automaticity by Low Quinidine Concentrations in Canine Purkinje Fibers Relationship to Potassium and Cycle Length , 1985, Circulation research.

[3]  A. Keren,et al.  Etiology, Warning Signs and Therapy of Torsade de Pointes: A Study of 10 Patients , 1981, Circulation.

[4]  K. Dangman,et al.  Studies on overdrive stimulation of canine cardiac Purkinje fibers: maximal diastolic potential as a determinant of the response. , 1983, Journal of the American College of Cardiology.

[5]  P. Schwartz,et al.  Sympathetic modulation of the relation between ventricular repolarization and cycle length. , 1991, Circulation research.

[6]  Paul F. Cranefield,et al.  Cardiac Arrhythmias: The Role of Triggered Activity and Other Mechanisms , 1988 .

[7]  D. Zipes,et al.  Alpha-adrenoceptor stimulation and blockade modulates cesium-induced early afterdepolarizations and ventricular tachyarrhythmias in dogs. , 1990, Circulation.

[8]  J. Spear,et al.  Autonomic modulation of ventricular arrhythmia in cesium chloride-induced long QT syndrome. , 1988, Circulation.

[9]  M. J. Janse,et al.  Refractory Period of the Dog's Ventricular Myocardium Following Sudden Changes in Frequency , 1969, Circulation research.

[10]  I. Cohen,et al.  K+ fluctuations in the extracellular spaces of cardiac muscle. Evidence from the voltage clamp and extracellular K+ - selective microelectrodes. , 1982, Circulation research.

[11]  R. Gilmour,et al.  Triggered activity as a mechanism for inherited ventricular arrhythmias in German shepherd Dogs. , 1996, Journal of the American College of Cardiology.

[12]  R. Aronson Mechanisms of Arrhythmias in Ventricular Hypertrophy , 1991 .

[13]  P. Coumel,et al.  Spontaneous sequences of onset of torsade de pointes in patients with acquired prolonged repolarization: quantitative analysis of Holter recordings. , 1995, Journal of the American College of Cardiology.

[14]  R. Cohen,et al.  Kinetics of Cycle Length Dependence of Ventricular Repolarization: , 1995, Journal of cardiovascular electrophysiology.

[15]  M. Franz,et al.  Cycle length dependence of human action potential duration in vivo. Effects of single extrastimuli, sudden sustained rate acceleration and deceleration, and different steady-state frequencies. , 1988, The Journal of clinical investigation.

[16]  D. Roden,et al.  Incidence and clinical features of the quinidine-associated long QT syndrome: implications for patient care. , 1986, American heart journal.

[17]  T. Colatsky,et al.  Effects of External Calcium, Calcium Channel‐Blocking Agents, and Stimulation Frequency on Cycle Length‐Dependent Changes in Canine Cardiac Action Potential Duration , 1980, Circulation research.

[18]  J. Jalife,et al.  Cardiac Electrophysiology: From Cell to Bedside , 1990 .

[19]  B. Surawicz,et al.  Cycle length effect on restitution of action potential duration in dog cardiac fibers. , 1983, The American journal of physiology.

[20]  E. Haber,et al.  The heart and cardiovascular system , 1986 .

[21]  H A Fozzard,et al.  Afterdepolarizations and triggered activity. , 1992, Basic research in cardiology.

[22]  M. Sanguinetti,et al.  Modulation of potassium channels by antiarrhythmic and antihypertensive drugs. , 1992, Hypertension.

[23]  R. Lazzara,et al.  Ventricular Tachyarrhythmias Related to Early Afterdepolarizations and Triggered Firing: Relationship to QT Interval Prolongation and Potential Therapeutic Role for Calcium Channel Blocking Agents , 1990 .

[24]  B. R. Jewell,et al.  Analysis of the effects of changes in rate and rhythm upon electrical activity in the heart. , 1980, Progress in biophysics and molecular biology.

[25]  M. Rosen,et al.  Effects of pacing on triggered activity induced by early afterdepolarizations. , 1984, Circulation.

[26]  M. Iliou,et al.  [Torsades de pointes]. , 1993, Archives des maladies du coeur et des vaisseaux.

[27]  A. L. Wit Afterdepolarizations and triggered activity: distinction from automaticity as an arrhythmogenic mechanism. , 1992 .

[28]  B. Katzung,et al.  Antiarrhythmic agents: the modulated receptor mechanism of action of sodium and calcium channel-blocking drugs. , 1984, Annual review of pharmacology and toxicology.

[29]  S. Priori,et al.  Sympathetic activation, ventricular repolarization and Ikr blockade: implications for the antifibrillatory efficacy of potassium channel blocking agents. , 1995, Journal of the American College of Cardiology.

[30]  Willis J. Tompkins,et al.  A Real-Time QRS Detection Algorithm , 1985, IEEE Transactions on Biomedical Engineering.