Drug Therapy For Torsade de Pointes

Torsade de Pointes. Torsade de pointes is an uncommon and unique type of ventricular tachycardia. It differs from other forms of ventricular tachycardia by its morphological features, underlying mechanism, and modes of therapy. Recognizing torsade de pointes is of major clinical importance, as standard antiarrhythmic regimens might not only be ineffective in abolishing this life-threatening arrhythmia but may aggravate it. Torsade de pointes is most commonly precipitated by QT prolonging drugs, mainly type IA antiarrhythmic therapy such as quinidine and disopyramide, and other antiarrhythmic agents are reported to cause torsade de pointes as well. Predisposing factors known to increase the likelihood of developing torsade de pointes are: electrolyte imbalance (hypokalemia, hypomagnesemia, or both) and slow heart rate induced either by sinus bradycardia or heart block. Treatment of torsade de pointes is aimed at shortening the QT interval. By acceleration of the heart rate, the QT interval is shortened, thus preventing the recurrence of the arrhythmia. Treatment of torsade de pointes includes: isoproterenol infusion, cardiac pacing, and intravenous atropine. Intravenous magnesium sulfate, a relatively new mode of therapy for torsade de pointes, was proven to be extremely effective and is now regarded as the treatment of choice for this arrhythmia.( Cardiovasc Electrophysiol, Vol. 4, pp. 206–210, April 1993 )     

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 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.     

临时人工心脏起搏治疗尖端扭转型室性心动过速

本组１０例尖端扭转型室速（Ｔｄｐ），８例为间歇依赖性长ＱＴ间期综合征（ＬＱＴＳ），２例为肾上腺素能依赖性ＬＱＴＳ。前者中有５例为缓慢心律，一入院即行临时人工心脏起搏术，再补钾补镁，余３例为药物治疗无效且出现血流动力学改变时行临时起搏；后者临时起搏术后给予静滴心得安治疗。１０例Ｔｄｐ均中止发作，无一例死亡。     

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.     

Clinical and therapeutic aspects of congenital and acquired long QT syndrome.

The long QT syndrome is characterized by prolongation of the corrected QT (QTc) interval on the surface electrocardiogram. It is associated with precipitation of a polymorphic ventricular tachycardia, torsade de pointes, which may cause sudden death. The syndrome is a disorder of cardiac repolarization caused by the alterations in the transmembrane potassium and sodium currents. Six genetic loci for the congenital forms of the syndrome have been identified; sporadic cases occur because of spontaneous mutations. Acquired causes of the long QT syndrome include drugs, electrolyte imbalance, toxins, marked bradycardia, subarachnoid hemorrhage, stroke, myocardial ischemia, protein-sparing fasting, autonomic neuropathy, and human immunodeficiency virus disease. Clinical symptoms are the result of the precipitation of torsade de pointes and range from such minor symptoms as dizziness to syncope and sudden death. Short-term treatment is aimed at preventing the recurrences of torsade de pointes and includes intravenous magnesium and potassium administration, temporary cardiac pacing, and correction of electrolyte imbalance; rarely, intravenous isoproterenol is indicated. Long-term management includes use of beta-blockers, permanent pacemaker placement, and cardioverter-defibrillator implantation. Asymptomatic patients are treated if under the age of 40 years at the time of diagnosis.     

Torsade de pointes tachycardia as a rare manifestation of acute enteroviral myocarditis

A patient with cardiac arrest and documented torsade de pointes ventricular tachycardia is presented in whom acute coxsackievirus B2 myocarditis was identified as the most likely underlying cardiac condition. This case shows that torsade de pointes may occur as a rare manifestation of viral myocarditis. Serial serological tests and endomyocardial biopsies may be helpful in establishing a diagnosis in such patients.


Keywords: torsade de pointes; ventricular tachycardia; viral myocarditis     

Electrophysiologic substrate of torsade de pointes: dispersion of repolarization or early afterdepolarizations?

Recent experimental and clinical studies suggest that torsade de pointes may be precipitated by early afterdepolarizations in the Purkinje or ventricular muscle fibers. This hypothesis offers an alternative to the earlier one that attributes torsade to the underlying dispersion of repolarization. This review lists the clinical conditions associated with torsade de pointes and examines the experimental background of the two proposed electrophysiologic substrates of torsade, namely, the dispersion of repolarization and the early afterdepolarizations. The strengths and weaknesses of the two hypotheses are compared in relation to the following characteristics of torsade de pointes: facilitation by slow heart rate, suppression by pacing, R on T phenomenon, difficulty of induction by programmed stimulation, aggravation by hypokalemia, manifestation of an idiosyncratic reaction to class IA antiarrhythmic drugs, spontaneous termination, suppression by magnesium salts and isoproterenol and induction by such drugs as sotalol, bepridil and prenylamine. It appears that most clinical observations can be explained by either mechanism, but in some cases difficulties are encountered for the afterdepolarization hypothesis.     

Pause-dependent torsade de pointes following acute myocardial infarction: a variant of the acquired long QT syndrome

OBJECTIVES: We report on a previously unrecognized form of the long QT syndrome (QT interval prolongation and pause-dependent polymorphic ventricular tachycardia [VT]) entirely related to myocardial infarction (MI). BACKGROUND: Polymorphic VT in the setting of acute MI generally occurs during the hyperacute phase, is related to ischemia, and is not associated with QT prolongation. Although QT prolongation after MI is well described, typical pause-dependent polymorphic VT (torsade de pointes) secondary to uncomplicated MI was previously unknown. METHODS: Of 434 consecutive admissions for acute MI, 8 patients had progressive QT prolongation that led to typical torsade de pointes. None of these patients had active ischemia or other known causes of QT prolongation. These patients were compared with 100 consecutive patients with uncomplicated MI who served as controls. RESULTS: The incidence of torsade de pointes following MI was 1.8% (95% confidence interval 0.8% to 3.6%). The QTc intervals of patients and controls were similar on admission. The QTc lengthened by day 2 in both groups, but more so in patients with torsade de pointes (from 470 +/- 46 to 492 +/- 57 ms [p < 0.05] and from 445 +/- 58 to 558 +/- 84 ms, respectively [p < 0.01]). Maximal QT prolongation and torsade de pointes occurred 3 to 11 days after infarction. Therapy included defibrillation, magnesium, lidocaine and beta-blockers. Three patients required rapid cardiac pacing. The long-term course was uneventful. CONCLUSIONS: Infarct-related torsade de pointes is uncommon but potentially lethal. An acquired long QT syndrome should be considered in patients recovering from MI who experience polymorphic VT as specific therapeutic measures are mandatory.     

Efficacy of Ventricular Pacing in the Treatment of an Arrhythmic Storm Associated with a Congenital Long QT Mutation

Long QT syndrome in the infant with 2:1 atrioventricular block is a malignant form of disease associated with frequent torsade de pointes in some cases. Those patients that do not respond to antiarrhythmic therapy are particularly challenging to manage. Ventricular pacing in this patient population has been shown to reduce arrhythmic events. We report a case of a newborn with frequent torsade de pointes requiring defibrillation and cardiopulmonary resuscitation with immediate shortening of the QTc interval with ventricular pacing and subsequent resolution of torsade de pointes.     

Akuttherapie lebensbedrohlicher tachykarder Rhythmusstörungen

Life-threatening supraventricular tachyarrhythmias include atrial fibrillation, atrial flutter, AV-nodal reentrant tachycardia with rapid ventricular response and preexcitation syndromes combined with atrial fibrillation. Ventricular tachyarrhythmias still remain one of the leading causes of death; these arrhythmias include monomorphic and polymorphic ventricular tachycardia, torsade de pointes tachycardia, ventricular fibrillation and ventricular flutter. In all patients with tachycardias, an attempt should be made to differentiate between narrow (QRS duration < 0.12 s) or wide QRS complex (QRS duration ≥ 0.12 s) tachycardias. In the assessment of patients (pts) with supraventricular/ventricular tachyarrhythmias, attention should be given to identify whether the tachycardia is associated with worsening angina or low cardiac output. In pts with narrow QRS complex tachycardias or pts with atrial fibrillation and preexcitation syndromes immediate synchronized cardioversion should be performed if signs or symptoms of instability (hypotension, evidence of end-organ dysfunction, worsening angina) exist. In pts with a stable hemodynamic situation, vagal maneuvers, adenosine or calcium channel blockers can be used. Management of atrial flutter usually centers on cardioversion or rapid atrial pacing to normal sinus rhythm. In the treatment of patients with deemed unstable ventricular tachycardia (VT), electrical cardioversion is the treatment of choice. In more stable patients, ajmaline is the preferred agent after myocardial infarction and lidocaine if myocardial ischemia is present. In pts with torsade de pointes tachycardias aggressive steps must be taken to prevent degeneration of this rhythm to ventricular fibrillation (VF). Magnesium sulfate has recently been demonstrated efficacious and is currently considered first-line drug therapy. Transcutaneous overdrive pacing should be attempted if magnesium is unsuccessful. The pt with pulseless VT or VF demands early electrical countershock.     

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.     

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.     

Torsade de pointes associated with bradycardia and takotsubo cardiomyopathy

Two cases of torsade de pointes associated with bradycardia and takotsubo cardiomyopathy are reported. In both cases, atrioventricular block preceded the occurrence of takotsubo cardiomyopathy. Bradycardia-induced QT interval prolongation seemed to be amplified by the occurrence of takotsubo cardiomyopathy, resulting in torsade de pointes. Temporary ventricular pacing at a high rate decreased the QT interval and prevented the recurrence of torsade de pointes. Because atrioventricular block recurred or persisted even after the resolution of takotsubo cardiomyopathy, the patients received permanent pacemakers.     

Early Afterdepolarizations in the Familial Long QTU Syndrome

Early Afterdepolarizations in Long QTU Syndrome. Torsade de pointes-induced syncopal episodes were almost invariably precipitated by emotional stress or menses in a 17-year-old female. U wave accentuation occurred during periods of heigbtened sympathetic tone. To document tbe role of early afterdepolarizations (EADs), monopbasic action potentials were recorded during ventricular extrasystoles and torsade de pointes occurring spontaneously and induced by ventricular pacing in tbe control state and after intravenous lidocaine. The effects of verapamil, propranolol, and epinephrine were observed. Our data show that: (1) EADs may play a significant role in the genesis of familial long QTU syndrome and torsade de pointes; (2) a faster ventricular pacing rate for a longer duration is related to tbe emergence of subsequent pause-dependent EADs, U waves, and torsade de pointes; (3) atrial pacing with Wenckebach block can provoke large postpause U waves, thus eliciting dual ventricular tachycardia; (4) EADs are enhanced by epinepbrine infusion in the absence of pause; and (5) EAD-triggered firing is inhibited by verapamil and propranolol but not by lidocaine. (J Cardiovasc Electrophysiol. Vol. 3, pp. 431–436, October 1992)     

Torsade de pointes complicating atrioventricular block: report of two cases

One patient with complete atrioventricular heart block and another with high-degree atrioventricular block, complicated by "torsade de pointes" are presented. Both patients were symptomatic. One had a syncopal episode and the other presented with signs and symptoms of congestive heart failure. The electrocardiographic phenomena of torsade de pointes was repeatedly recorded. No other known predisposing factors for torsade de pointes were identified. The use of right ventricular endocardial pacing suppressed the paroxysms in both patients.     

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.     

Limited effect of magnesium sulphate on torsades de pointes ventricular tachycardia

A patient with thioridazine-induced torsades de pointes ventricular tachycardia treated with magnesium sulphate is presented. Due to incessant recurrence of tachycardias it was possible to observe the time course of the effect of 1 g intravenous doses. Suppression of torsades de pointes lasted at best for no more than 18 min and a maintenance infusion was not effective without overdrive pacing. Magnesium sulphate may have value as first aid therapy for drug-induced torsades de pointes ventricular tachycardia. However, its effect disappears rapidly, and, therefore, should not alone be relied on as prophylactic treatment.     

Quinidine-induced long QTU interval and torsade de pointes: role of bradycardia-dependent early afterdepolarizations

Right ventricular endocardial monophasic action potential recordings were obtained in a patient with a qunidine-induced long QTU interval and polymorphic ventricular tachycardia of the torsade de pointes type. The recording showed a deflection on phase 3 repolarization characteristic of early afterdepolarization. The early afterdepolarization was synchronous with the U wave in surface electrocardiographic leads and there was a strong correlation between the amplitude of both waves. A strong correlation was also present between the cardiac cycle length and the U wave amplitude with larger amplitudes after longer cycles. Ventricular ectopic beats occurred only after long cycle lengths and seemed to arise close to the peak of the U wave and early afterdepolarization. However, there was no correlation between the amplitude of the U wave or early afterdepolarization and the occurrence of ectopic beats. Rapid ventricular pacing resulted in suppression of the ectopic rhythm associated with suppression of both the U wave and the early afterdepolarization. This case provides the first evidence to suggest that a quinidine-induced long QTU interval and torsade de pointes may be related to bradycardia-dependent early afterdepolarizations, although other factors may be involved in triggering the arrhythmia.     

Suppression of amiodarone-induced torsade de pointes by landiolol in a patient with atrial fibrillation-mediated cardiomyopathy

An elderly Japanese woman developed acute decompensated heart failure caused by persistent atrial fibrillation (AF) and left ventricular systolic dysfunction. Approximately 6 days after starting intravenous administration of amiodarone (600 mg/day) for maintaining sinus rhythm after cardioversion of AF, electrocardiograms revealed a prolonged QT interval associated with torsade de pointes (TdP). The amiodarone-induced TdP disappeared after intravenous administration of landiolol plus magnesium and potassium, without discontinuation of amiodarone or overdrive cardiac pacing, although the prolonged QT interval persisted. To the best of our knowledge, this is the first report that landiolol could be effective for amiodarone-induced TdP.