A practical approach to torsade de pointes

The term torsade de pointes refers to polymorphic ventricular tachycardia that occurs in the setting of an abnormally long QT interval. While the most common cause is treatment with QT prolonging drugs, torsade de pointes also occurs in the congenital long QT syndromes and in the setting of acquired heart block or severe electrolyte disturbance, notably hypokalemia. Among QT prolonging drugs that cause torsade de pointes, both antiarrhythmics and “noncardioactive” drugs have been recognized. The electrocardiographic features of torsade de pointes include labile QT intervals, prominent U waves, and a “pause-dependent” onset of the arrhythmia. Treatment consists of recognition of the syndrome, correction of underlying electrolyte abnormalities, and withdrawal of any offending drugs. Magnesium, isoproterenol, or cardiac pacing provides specific antiarrhythmic therapy in torsade de pointes.     

QT interval prolongation, torsade de pointes and renal disease

Torsade de pointes is a form of polymorphic ventricular tachycardia occurring in a setting of prolonged QT interval on surface electrocardiogram. Several non-antiarrhythmic drugs including antibiotic and antipsychotic agents have been shown to prolong cardiac repolarization predisposing to torsade de pointes ventricular tachycardia. Blockade of the delayed rectifier (repolarising) potassium current and drug interactions with inhibitors of the cytochromes P450 (CYP)-mediated metabolism are the most common underlying mechanisms. Many antiarrhythmic drugs have been also implicated in prolonging QT interval and triggering torsades de pointes, especially during chronic therapy or in case of acute high dose toxicity. Progressive renal disease is associated from the earliest stages with increased QT interval and dispersal and with an increased risk of cardiovascular death, specifically sudden death. It has also been reported that cCorrected QT (QTc) interval prolongation and torsade de pointes are associated with end-stage renal disease (ESRD) and that they can be a cause of sudden death in ESRD. We present a case of torsade de pointes in a 82-year-old Italian woman with chronic renal failure.     

Heart rate variability in human immunodeficiency virus-positive individuals

Torsade de pointes is a form of polymorphic ventricular tachycardia occurring in a setting of prolonged QT interval on surface electrocardiogram. Congenital causes of prolonged QT interval occur in individuals with genetic mutations in genes that control expression of potassium and sodium channels and acquired causes are numerous, predominantly drugs causing prolonged QT interval by blockade of potassium channels. Among the drugs, antiarrhythmic agents most notably quinidine, sotalol, dofetilide and ibutilide have the potential to induce the fatal torsade de pointes. Many non-antiarrhythmic drugs can also cause torsade de pointes. Although it is important to distinguish between the congenital and the acquired forms of long QT syndrome as the later can often be reversed by correction of the underlying disorder or discontinuation of the offending drug, both forms are not mutually exclusive. Clinical considerations and management of torsade de pointes are described.     

Prevention of torsade de pointes in the congenital long QT syndrome: use of a pause prevention pacing algorithm

Torsade de pointes in the congenital long QT syndrome (LQTS) is often pause dependent. Thus, the main goal of pacemaker treatment in the LQTS may be the prevention of pauses that facilitate the onset of torsade de pointes. A pause prevention pacing algorithm (rate smoothing) was used for arrhythmia prevention in a 14 year old girl with congenital LQTS. By temporarily increasing the pacing rate after spontaneous premature beats, rate smoothing down of 18% prevented postextrasystolic pauses, pause related T-U changes, and recurrence of pause induced torsade de pointes. Rate smoothing is a potentially useful tool that ought to be evaluated for the prevention of torsade de pointes in the LQTS.

Keywords: long QT syndrome; torsade de pointes; ventricular fibrillation; ventricular tachycardia; pacing     

Torsade de pointes

The polymorphic ventricular tachycardia torsade de pointes can occur in the congenital long QT syndromes or as a consequence of therapy with QT-prolonging drugs. The latter can include not only antiarrhythmic drugs such as quinidine, but also a number of drugs which are not usually considered to have major cardiovascular effects: these include nonsedating antihistamines, such as terfenadine; antibiotics such as erythromycin; and neuroleptics such as thioridazine. The electrocardiographic hallmark of both the congenital and acquired forms of the long QT syndrome is marked QT(U) lability, particularly as a function of heart rate. The underlying mechanism is thought to be triggered activity arising as a consequence of early afterdepolarizations. An understanding of the basic mechanism has led to an understanding of the effective forms of therapy, which include maneuvers to include the heart rate (pacing, isoproterenol) as well as maneuvers which may not necessarily alter the QT interval but may prevent the arrhythmia (magnesium, beta blockers). Intensive study of the clinical features and basic mechanisms underlying torsade de pointes has led to the definition of a new mechanism for cardiac arrhythmias; understanding such mechanisms may ultimately lead to the development of safer antiarrhythmic therapy.     

Polymorphous ventricular tachycardia associated with normal and long Q-T intervals

Polymorphous ventricular tachycardia may occur in the setting of either a normal or a prolonged Q-T interval. Torsade de pointes is a form of polymorphous ventricular tachycardia in which the polarity of the QRS complex exhibits phasic alterations in both axis and rate. Traditionally, torsade de pointes has been described in association with a variety of congenital and acquired (including drug and metabolic) causes of Q-T prolongation. The distinction between torsade de pointes and those polymorphous ventricular tachycardias occurring in patients with a normal Q-T interval has important therapeutic implications. The former requires strict avoidance of all drugs that may potentially further delay repolarization, including class I antiarrhythmic agents; immediately, the initiation of cardiac pacing is often necessary for control of arrhythmia, and on a long-term basis, sympathetic nervous blockade is often efficacious. In contrast, the polymorphous ventricular tachycardias with a normal Q-T interval usually respond to conventional therapy, including administration of class I antiarrhythmic agents. Thus, the management of polymorphous ventricular tachycardia should be based on the presence or absence of associated repolarization alterations rather than on the morphologic features of the tachycardia. Unfortunately, recent advances in basic and clinical electrophysiology have not yet elucidated the pathophysiologic basis for these arrhythmias, although this is an area of active investigative interest.     

Iatrogenic torsade de pointes induced by thioridazine]

Torsade de pointes is a form of polymorphous ventricular tachycardia in which the polarity of the QRS complex exhibits phasic alterations in both axis. Traditionally, torsade de pointes has been described in association with a congenital or acquired (including drug and metabolic) causes of QT prolongation. Clinical outcomes range from asymptomatic, self-terminating arrhythmias to ventricular fibrillation resulting in cardiac arrest. For the treatment of torsade de pointes, the conventional antiarrhythmic drugs cannot be relied on, cardiac pacing should be instituted as soon as possible; however, as this technique may not always be immediately available, isoproterenol infusion may be the first-choice treatment. Potassium and magnesium repletion appear to be essential in abolishing drug-induced torsade de pointes. This report describes a case of thioridazine-induced torsade de pointes treated efficaciously with magnesium sulphate and overdrive right ventricular pacing.     

Torsade de pointes induced by ajmaline

Ajmaline, a reserpine derivative, is an effective class I antiarrhythmic agent. Herein we report two cases of ajmaline-induced abnormal QT prolongation accompanied by polymorphic ventricular tachycardia of the torsade de pointes type. Since ajmaline is increasingly used for the acute termination of wide complex tachycardia and as a diagnostic tool after syncope and in patients with idiopathic ventricular tachyarrhythmias, our observations suggest that caution should be exercised with regard to the effects of the drug on the QT interval and its potency to induce proarrhythmia of the torsade de pointes type.     

Torsade de pointes induced by terfenadine in a patient with long QT syndrome

Torsade de pointes is a form of polymorphic ventricular tachycardia that is associated with prolongation of the QT interval. Although torsade de pointes is found in many clinical settings, it is mostly drug induced. Similar problems have been described with nonsedating H₁-receptor antagonists, such as astemizole and terfenadine. Terfenadine is a widely used antihistamine. The authors report a case of torsade de pointes in a patient with a possible congenital sporadic form of QT interval prolongation who was receiving a therapeutic dose of terfenadine.     

Torsade de pointes: the long-short initiating sequence and other clinical features: observations in 32 patients

The clinical setting, precipitating factors, electrocardiographic features and response to treatment of 32 patients with torsade de pointes were reviewed. Thirty-one patients had underlying cardiac disease and 30 patients had a previous underlying cardiac arrhythmia. Antiarrhythmic medications, often in association with electrolyte abnormalities (such as hypokalemia and hypomagnesemia) were the most common precipitating factors. In 22 of 26 patients, the serum drug levels of the antiarrhythmic agents were found to be within the therapeutic range. However, before the administration of agents known to prolong the QT interval, 20 of the 32 patients had, either alone or in combination, baseline prolongation of the QT interval, hypokalemia or hypomagnesemia. All patients had QTc interval prolongation (mean 0.59 second) immediately before the development of torsade de pointes. Marked lability of T wave morphology was frequently noted. Cardiac pacing was the only consistently effective mode of therapy. A characteristic long-short ventricular cycle length as the initiating sequence was found in 41 of 44 episodes of torsade de pointes. Reported data support the high frequency of this electrocardiographic feature of torsade de pointes in which its onset could be analyzed. It is suggested that this electrocardiographic characteristic will aid in both establishing the diagnosis of torsade de pointes and distinguishing it from other polymorphic forms of ventricular tachycardia.     

Torsade de pointes associated with moxifloxacin: a rare but potentially fatal adverse event

Torsade de pointes occuring due to a long QT interval is a rare but potentially fatal arrhythmia. Acquired long QT develops most commonly because of drugs that prolong ventricular repolarization. It has been reported that fluoroquinolone antimicrobials prolong the corrected QT interval but rarely cause torsade de pointes. A patient with torsade de pointes risk factors (female sex, advanced age, extreme bradycardia and renal failure) who developed the condition on the fourth day of 400 mg/day of oral moxifloxacin treatment is presented. After the moxifloxacin was stopped, the corrected QT interval normalized and a permanent cardiac pacemaker was implanted. During 11 months of follow-up, arrhythmia did not recur.     

Terminology of torsades de pointes

Marked prolongation of the QT interval may be associated with life-threatening ventricular tachycardia. The ventricular tachycardia has a polymorphous appearance and is usually induced by antiarrhythmic drugs. This peculiar type of ventricular tachycardia was termed by Desserstenne torsades de pointes because of its twisting ORS axis. The main reason to give this entity a special name that differentiates it from other types of ventricular tachycardia is the unique therapeutic approach to its treatment. Torsades de pointes can be suppressed by interventions that shorten the QT interval by increasing the heart rate, such as ventricular or atrial pacing, isoproterenol infusion, or atropine. Recently intravenous magnesium was also shown to be extremely effective. If torsades de pointes is treated as a conventional ventricular tachycardia by drugs that may further prolong the QT interval, it may lead to fatal results. To draw the attention of physicians to this unusual form of ventricular tachycardia, we suggest that the term torsades de pointes be kept. This specific diagnosis will hopefully guide the treating physician in selecting the appropriate mode of therapy.     

Detailed analysis of 24 hour ambulatory electrocardiographic recordings during ventricular fibrillation or torsade de pointes

Although the terminal cardiac rhythm is often well documented in many cases of sudden cardiac death, the antecedent or premonitory arrhythmias are usually not retrievable. The ambulatory electrocardiographic recordings of 12 patients who sustained ventricular fibrillation or torsade de pointes while wearing a long-term electrocardiographic monitor were analyzed in detail. A printout of the entire electrocardiographic recording was made and hand counts of ventricular arrhythmias were correlated with heart rate, QTc interval, RR interval preceding ventricular fibrillation or torsade de pointes and (RR')/QT initiating ventricular fibrillation or torsade de pointes. Common ambulatory electrocardiographic features in these 12 patients experiencing ventricular fibrillation or torsade de pointes included: 1) a period of high density of increasingly frequent or complex ventricular arrhythmias, or both, preceding ventricular fibrillation or torsade de pointes (11 patients); 2) R on T beats frequently initiating ventricular fibrillation or torsade de pointes (9 patients); and 3) repolarization abnormalities present for several hours before ventricular fibrillation or torsade de pointes (7 patients). No consistent relation between the RR and RR' interval initiating ventricular fibrillation or torsade de pointes was found; no consistent alteration in heart rate occurred before ventricular fibrillation or torsade de pointes. Thus, ventricular arrhythmias leading to sudden death in an ambulatory population do not occur in isolation but are preceded by a period of increased ventricular ectopic activity. Future guidelines for assessment of antiarrhythmic drug efficacy should include an evaluation of a drug's impact not only on ectopic beat frequency but also on arrhythmia density.     

Dofetilide induced torsade de pointes: Mechanism,risk factors and management strategies

Dofetilide is an effective antiarrhythmic agent for conversion of atrial fibrillation and atrial flutter as well as maintenance of sinus rhythm in appropriately selected patients. However, as with other antiarrhythmic agents, proarrhythmia is a known adverse effect. The risk of dofetilide induced torsade de pointes (Tdp) is low when used with strict dosing criteria guided by renal function, QT interval and concomitant drug therapy. Benefit from dofetilide use must be individualized and weighed against the side effects and the role of other available treatment options. In this review, we discuss the underlying mechanism, risk factors and precautionary measures to avoid dofetilide induced QT prolongation and ventricular tachycardia/Tdp. We suggest a scheme for the management of QT prolongation, ventricular arrhythmia and Tdp as well.     

Torsade de pointes due to coxsackie B3 myocarditis

Viral myocarditis may present with a variety of electrocardiologic aberrations. Torsade de pointes, a potentially malignant ventricular arrhythmia associated with prolongation of the QT interval has not been described in patients with acute viral myocarditis. This report details this finding in a patient with coxsackie B3 myocarditis in whom symptomatic torsade de pointes was documented.     

Torsade de Pointes Complicating the Treatment of Bleeding Esophageal Varices: Association with Neuroleptics, Vasopressin, and Electrolyte Imbalance

Torsade de pointes is an unusual life-threatening ventricular arrhythmia that has been associated with vasopressin, neuroleptic drugs, and electrolyte imbalances, including hypokaleniia and hypomagnesemia. Over a 9-month period, we observed torsade de pointes in three patients with cirrhosis and bleeding esophageal varices who did not have prior cardiac disease. All had received endoscopic sclerotherapy and continuous infusions of vasopressin and nitroglycerin. For sedation, two patients received haloperidol and one droperidol. In addition, two patients had either hypokalemia or hypomagnesemia. In all three patients, there was prolongation of the electrocardiographic QT interval and a "long-short" initiating sequence followed by ventricular tachycardia with torsade de pointes morphology. All were successfully cardioverted; there was one late death due to aspiration and septicemia. We conclude that cirrhotics with variceal hemorrhage may be at increased risk of developing this arrhythmia in the setting of treatment with vasopressin, sedation with neuroleptic drugs, and electrolyte abnormalities. We urge close monitoring of these patients for cardiac arrhythmia and recommend that neuroleptics be used cautiously, if at all.     

Congenital complete heart block associated with QT prolongation.

The coexistence of congenital complete heart block and QT prolongation represents a special type of arrhythmia. The electrophysiological and clinical characteristics of this syndrome were studied in eight patients suffering from congenital AV block and QT prolongation. Data from 22 patients suffering from congenital complete heart block only, served as a control. In the study group, the appearance of a torsade de pointes type of ventricular tachycardia could regularly be observed and the tachycardial attack could usually be provoked by ventricular extrastimuli. The corrected QT time was markedly prolonged; on ventricular stimulation, at higher pacing rates the QT interval shortened, but remained significantly higher than in the control group. Syncopal attacks--with the character of polymorphic tachycardia--appeared in each patient of the study group while occurring in only three patients from the control group. Patients were given pacemaker implants (using a higher pacing rate) and long-term administration of beta-receptor blockers. The outcome was favourable; no ventricular tachycardia or syncopal attack was observed in the follow-up period.     

Treatment of torsade de pointes with intravenous magnesium in idiopathic long QT syndrome.

A middle aged woman with idiopathic long QT syndrome was found to have repetitive ventricular tachycardia of the "torsade de pointes" type. The arrhythmia was resistant to mexiletine and lidocaine, but was controlled by intravenous magnesium sulfate (MgSO4). The recurrent attacks were abolished by a bolus of 2.0 g MgSO4, and extremely prolonged QTU interval was reduced by intravenous infusion of 5 mg/min MgSO4 for 36 h. This case shows the effectiveness of intravenous magnesium in controlling the attack of torsade de pointes in patients with idiopathic long QT syndrome.     

Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhythmic drugs and amiodarone.

BACKGROUND. Patients with a history of class Ia drug-induced torsade de pointes have been treated with chronic amiodarone without recurrence of torsade de pointes despite comparable prolongation of the QT interval. We hypothesized that in such patients, class Ia drugs cause nonhomogeneous prolongation of cardiac repolarization times, whereas amiodarone causes homogeneous prolongation of cardiac repolarization times. METHODS AND RESULTS. Thirty-eight consecutive patients who received both class Ia drug therapy and chronic amiodarone therapy were evaluated. Standard 12-lead ECGs at baseline and during each therapy were used to calculate precordial QT interval dispersion (maximum QT in leads V1 through V6 minus minimum QT leads V1 through V6) as a measure of regional variabilities in ventricular repolarization times. Nine of these patients had torsade de pointes during class Ia drug therapy. In these nine patients, class Ia drug therapy and amiodarone significantly prolonged the maximum QT interval to comparable extents. However, class Ia drug therapy but not amiodarone therapy significantly increased precordial QT interval dispersion (101 +/- 37 versus 49 +/- 26 msec; baseline, 44 +/- 12 msec; p = 0.002). In the 29 patients without class Ia drug-induced torsade de pointes, neither class Ia drug therapy nor amiodarone therapy significantly increased QT interval dispersion (50 +/- 6 versus 69 +/- 7 msec; baseline, 54 +/- 5 msec). None of the patients with class Ia drug-induced torsade de pointes had recurrent torsade de pointes during chronic amiodarone therapy. CONCLUSIONS. An increase in regional QT interval dispersion during class Ia antiarrhythmic drug therapy is associated with torsade de pointes. Chronic amiodarone therapy in patients with a history of class Ia drug-induced torsade de pointes produces comparable maximum QT interval prolongation but does not increase QT interval dispersion. This characteristic may explain its apparent safe use in patients with a history of class Ia drug-induced torsade de pointes.     

Torsade de pointes complicating acute myocardial infarction: the importance of autonomic dysfunction as assessed by heart rate variability.

Torsade de pointes is a polymorphic ventricular tachycardia associated with QT-interval prolongation rarely reported to occur in the setting of an acute myocardial infarction. Autonomic dysfunction has been implicated as a major stimulus for the development of this dysrhythmia. We describe the case of an 80-year-old woman who presented with an acute myocardial infarction and progressive QT-interval lengthening. An 89-beat run of torsade de pointes occurred during the time of the peak creatine phosphokinase (CPK) without electrolyte abnormalities or antiarrhythmic therapy. Assessment of autonomic tone using power spectral analysis of two consecutive 24-h Holter recordings was performed indicating that a transient decrease in heart rate variability and increase in sympathetic tone preceded the tachyarrhythmia. This case shows the potential usefulness of heart rate variability analysis as a marker for autonomic dysfunction and arrhythmogenesis, particularly during myocardial ischemia.