Torsades de pointes and long QT syndromes

Author: Louis F. Janeira
Date: Oct, 1995

Although long QT intervals had previously been associated with syncope and sudden death, it was not until 1966 that the actual arrhythmia associated with this syndrome was identified as a polymorphic form of ventricular tachycardia. Its electrocardiographic appearance was described as a "twisting of the points" or, in French, "torsades de pointes."[1]

Both polymorphic and monomorphic ventricular tachycardia may occur in association with a normal QT interval. Polymorphic ventricular tachycardia may occur, for instance, during myocardial ischemia or infarction, and it may be confused with ventricular fibrillation. The designation "torsades de pointes" should be employed only when polymorphic ventricular tachycardia is associated with long QT intervals.[1]

Prevalence and Risk Factors

The exact incidence of torsades de pointes remains speculative, but the condition is thought to be more unrecognized than rare.[2] The arrhythmia has been reported in all age groups, from newborns3 to the very old.4 Evidence of coexisting structural heart disease is often absent,[5,6] especially in the congenital form of the arrhythmia. Approximately 0.25 percent of deaf-mute children are born with a long QT interval. These individuals have been reported to represent about 30 percent of all patients with torsades de pointes and long QT intervals.[2]

The overall mortality rate for patients with prolonged QT syndromes has been estimated to be 1 to 2 percent per year.[7] Some patients appear to have a benign course and have only one or two episodes in their entire life. Others tend to have recurrent symptomatic episodes.[2]

Independent risk factors for death due to torsades de pointes include female gender, congenital deafness, a history of syncope or resuscitated arrest, and a family history of sudden death. Few, if any, episodes have been reported during pregnancy or in the postpartum period.7 The reason for the lack of occurrence in association with pregnancy remains a mystery but may perhaps be explained, at least in part, by the usual avoidance of drugs during pregnancy. Agents known to prolong the QT interval can predispose individuals to torsades de pointes.

Characteristics

The polymorphic configuration in torsades de pointes is caused by changes in the QRS axis, as if the QRS complexes were being twisted around the isoelectric line (Figure 1). These polarity oscillations typically occur every three to 20 beats. Characteristically, torsade de pointes occurs in clusters, and it tends to be rapid and self-terminating. The ventricular rhythm is usually irregular, and rates from 160 to over 300 have been described.[4,8]

Since the ventricular rate is typically rapid, sustained torsades de pointes is almost always poorly tolerated. Patients often complain of symptoms that are related to hemodynamic compromise from low cardiac output. These include dizziness, angina, shortness of breath and syncope. Torsades de pointes may degenerate into ventricular fibrillation and sudden death.[3,4,8-10]

The QT Interval

The QT interval is measured from the QRS complex (i.e., the beginning of the Q wave or, if the Q wave is absent, the beginning of the R wave) to the end of the T wave. If a U wave is merged with the T wave, this should be included in the measurement, and the interval in this situation is called the QTU interval.

The measured QT interval ([QT.sub.m]) should be corrected to the heart rate ([QT.sub.c]). The best way to make this calculation is under current dispute. Many formulas have appeared in the literature, but the following is still the one most commonly used: QTc = QTm/RR, where RR (in seconds) indicates the interval between the two R waves preceding the measured QT31

In the absence of intraventricular conduction delays, the normal corrected QT interval ([QT.sub.c]) is 420 to 440 msec. When bundle branch block is present, proper calculation of the [QT.sub.c] is still unsettled.[7] The QT interval should be measured in several leads, and the longest one ([QT.sub.max]) should be used. The anteroseptal leads are often closest to the [QT.sub.max].[12] As a rough guide, if the [QT.sub.m] is greater than half the preceding RR interval, the [QT.sub.c] is likely to be prolonged, though this applies best when the heart rate is less than 100 beats per minute (Figure 2).

Torsades de pointes induction depends not only on QT prolongation but also on the T-wave distortion.[13] Quinidine-induced torsades de pointes (quinidine syncope) has been reported to be accompanied by minimal increases in the QT interval,[13,14] whereas hypocalcemia is an infrequent cause of torsades de pointes despite marked QT prolongation.[15,16] However, quinidine induces T-wave distortions as it prolongs repolarization, whereas hypocalcemia only lengthens the ST segment. T-wave distortions are believed to be essential for torsades de pointes to be initiated, and they indicate a greater vulnerability to the development of the arrhythmia.[5,13,17-19] These distortions may take the form of notched T waves, biphasic T waves or T-wave alternans (i.e., T-wave distortions that vary from beat to beat).

Researchers have tried to correlate the QT interval prolongation with the subsequent risk of torsades de pointes. A measured QT interval of more than 600 msec poses a high risk.[20] Patients with a QTc between 500 and 600 msec are at moderate risk for torsades de pointes.[21,22] If the QTc is less than 500 msec, the risk of torsades de pointes appears to be low.

Regardless of the QTc, other factors that may increase this interval should be avoided in susceptible patients. This includes, for instance, the use of diuretics that may have the potential to cause significant depletion of potassium and/or magnesium. Likewise, patients should be asked to report episodes of prolonged diarrhea or anorexia. The concomitant use of different agents that increase the QT interval should only be used if absolutely necessary. In such cases, frequent ECGs should be obtained to determine the [QT.sub.c].

Etiology of Long QT Intervals

On the basis of the clinical findings and response to therapy, long QT intervals can be separated into two distinct major categories: acquired QT prolongation, and idiopathic and congenital QT prolongation.

ACQUIRED QT PROLONGATION

Acquired QT prolongation is most frequently induced by drugs or electrolyte disturbances. The most common culprits are class IA antiarrhythmic agents, especially quinidine. Torsades de pointes in these patients is often not dose-dependent. In fact, 50 percent of patients who develop torsades de pointes due to quinidine therapy do so before therapeutic levels are achieved.[13,14,20]

Established causes of acquired long QT intervals are listed in Table 1. Torsades de pointes in this group is characterized by its association with bradyarrhythmias or pauses in the rhythm that create long-short RR cycles, especially if T-wave distortions are induced (Figures 3a and 3b).[23]

TABLE 1Causes of Acquired (Pause-Dependent) QT Prolongation

Therapy

Therapy for torsades de pointes depends on the etiology of the QT prolongation.

ACQUIRED TORSADES DE POINTES

In the acquired type, the most important step is to withdraw the offending drug or correct other potential etiologic factors. If the patient presents with hemodynamically compromising torsades de pointes, defibrillation is required. However, until the underlying cause is corrected, torsades de pointes may very likely recur. Therefore, electrical cardioversion must be accompanied by other interventions that protect the heart against the arrhythmia and/or shorten the long QT interval.[15,24]

For most patients, magnesium sulfate is recommended as first-line therapy for torsades de pointes with QT interval prolongation.[25,26] The dose is 2 g of magnesium sulfate, given intravenously over one to five minutes, with a second bolus given, if necessary, five to 15 minutes later. If needed, patients can receive a continuous intravenous infusion of magnesium sulfate (3 to 20 mg per minute) for up to 48 hours or until the QT interval has been normalized by the correction of any obvious underlying factors.[25] The efficacy of magnesium sulfate in treating the arrhythmia is independent of the patient's pretreatment magnesium level. Furthermore, magnesium sulfate therapy does not, in itself, shorten the QT interval.

When bradyarrhythmias and pauses are observed, they also must be treated. Prompt results can usually be achieved with atropine or isoproterenol (Isuprel) while temporary pacing measures are being readied.[20,24,26] Temporary pacing works by increasing the heart rate, which shortens the QT interval. External pacing, while avoiding the risk of transvenous pacemaker insertion, frequently is not a good option, since most conscious patients find this method uncomfortable. Both atrial and ventricular pacing have been used. If atrioventricular conduction is preserved, atrial pacing is preferred, since it is more physiologic.

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Torsades de pointes: prevention and therapy. Cardiovasc Drugs Ther 1991;5: 509-13. [22.] Rao KA, Adlakha A, Verma-Ansil B, Meloy TD, Stanton MS. Torsades de pointes ventricular tachycardia associated with overdose of astemizole. Mayo Clin Proc 1994;69:589-93. [23.] Jackman WM, Szabo B, Friday KJ, Margolis PD, Moulton K, Wang X, 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. J Cardiovasc Electrophysiol 1990;3:170-95. [24.] Miller DS, Blount AW Jr. Quinidine-induced recurrent ventricular fibrillation: (quinidine-syncope) treated with transvenous pacemaker. South Med J 1971;64:597-601 . [25.] Tzivoni D, Banai S, Schuger C, Benhorin J, Keren A, Gottlieb S, et al. Treatment of torsades de pointes with magnesium sulfate. Circulation 1988;77:392-7. [26.] Banai S, Tzivoni D. Drug therapy for torsade de pointes. 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The long QT syndrome: effects of drugs and left stellate ganglion block. Am Heart J 1982;104(2 Pt 1):194-8. [34.] Mirowski M, Reid PR, Mower MM, Watkins L, Gott VL, Schauble JF, et al. Termination of malignant ventricular arrhythmias with an implanted automatic defibrillator in human beings. N Engl J Med 1980;303:322-4. [35.] Yanowitz F, Preston JB, Abildskov JA. Functional distribution of right and left stellate innervation to the ventricles. Circ Res 1966;18:416-28. [36.] Crampton R. Preeminence of the left stellate ganglion in the long QT syndrome. Circulation 1979;59:769-78.

LOUIS F. JANEIRA, M.D. is chief of the cardiac electrophysiology section at St. Mary's Medical Center in Evansville, Ind., where he is also in private practice as a cardiologist-electrophysiologist. Dr. Janeira completed his training in cardiology and electrophysiology at Deborah Heart and Lung Center, Browns Mill, N.J.

Address correspondence to Louis F. Janeira, M.D., Section of Cardiac Electrophysiology, St. Mary's Medical Center, 1400 Professional Blvd., Evansville, IN 47714. Figure 3b from Jackman WM, Szabo B, Friday KJ, Margolis PD, Moulton K, Wang X, 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. J Cardiovasc Electrophysiol 1990;3:174. Used with permission.

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