AUTHOR AND EDITOR INFORMATION

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• Clinical
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• Treatment
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• Follow-up
• Miscellaneous
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INTRODUCTION

Section 2 of 11  

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• Follow-up
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Background

Torsade de pointes, literally meaning twisting of points, is a distinctive form of polymorphic ventricular tachycardia (VT) characterized by a gradual change in the amplitude and twisting of the QRS complexes around the isoelectric line. Torsade de pointes (torsade) is associated with a prolonged QT interval, which may be congenital or acquired. It usually terminates spontaneously but frequently recurs and may degenerate into sustained VT and ventricular fibrillation.

Pathophysiology

The association between torsade and a prolonged QT interval has long been known, but the mechanisms involved at the cellular and ionic levels have been made clearer in approximately the last decade. The abnormality underlying both acquired and congenital long QT syndromes is in the ionic current flow during repolarization, which affects the QT interval. Various studies support the concept that prolongation of the repolarization delays the inactivation of the ion channels responsible for the inward flow of positive depolarizing currents. This leads to a further delay in repolarization and causes early after depolarization (EAD), the triggering event for torsade. The following phases are described:

• Phase 1: During initial upstroke of action potential in a normal cardiac cell, a rapid net influx of positive ions (Na⁺ and Ca⁺⁺) occurs, which results in the depolarization of the cell membrane. This is followed by a rapid transient outward potassium current (Ito), while the influx rate of positive ions (Na⁺, Ca⁺⁺) declines. This represents the initial part of the repolarization, or phase 1.
• Phase 2 is characterized by the plateau, the distinctive feature of which is the cardiac repolarization. The positive currents flowing inward and outward become almost equal during this stage.
• Phase 3 of the repolarization is mediated by activation of the delayed rectifier potassium current (IK) moving outward while the inward positive current decays. If a slow inactivation of the Ca⁺⁺ and Na⁺ currents occurs, this inward "window" current can cause single or repetitive depolarization during phases 2 and 3 (ie, EADs). These EADs appear as pathologic U waves on a surface ECG, and, when they reach a threshold, they may trigger ventricular tachyarrhythmias.

These changes in repolarization do not occur in all myocardial cells. The deep endocardial region and midmyocardial layer (composed of M cells) of the ventricle are more prone to prolongation of repolarization and EADs because they have a less rapid delayed rectifier potassium current (IKr), while other regions might have short or normal cycles. This heterogeneity of repolarization in the myocardial cells promotes the spread of triggered activity, which is initiated by EADs by a reentrant mechanism and currently is thought to be responsible for the maintenance of torsade.

Mortality/Morbidity

Torsade is a life-threatening arrhythmia and may present as sudden cardiac death in patients with structurally normal hearts.

Race

For both sexes, the corrected QT interval is longer in white persons than in black persons, thus explaining the lower susceptibility to acquired torsade in black persons.

Sex

Females are more prone to the development of torsade than males because they have longer QT intervals.

Age

Torsade occurs in patients of a wide age range, from newborn to 86 years. If it occurs at an early age, the cause usually is due to congenital long QT syndrome. In later years, the cause usually is due to acquired long QT syndrome.

CLINICAL

Section 3 of 11  

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History

Patients with torsade usually present with recurrent episodes of palpitations, dizziness, and syncope; however, sudden cardiac death can occur with the first episode. Nausea, cold sweats, shortness of breath, and chest pain also may occur but are nonspecific and can be produced by any form of tachyarrhythmia.

• In a young patient with torsade, a diagnosis of congenital long QT syndrome should be considered, especially if a family history of sudden cardiac death or sudden infant death syndrome is present. In these patients, episodes of torsade are triggered by adrenergic stimulation such as stress, fear, or physical exertion, but other predisposing factors also should be considered.
• Patients with Jervell and Lange-Nielsen syndrome commonly have congenital sensorineural deafness representing an autosomal dominant pattern of inheritance for cardiac abnormalities, whereas deafness usually is autosomal recessive.
• Another form of familial or congenital long QT syndrome is Romano-Ward syndrome, in which hearing is normal and an autosomal dominant pattern of inheritance is observed.
• Patients with acquired long QT syndrome usually develop torsade during periods of bradycardia.
• The most common causes of acquired long QT syndrome are medications and electrolyte disorders (eg, hypokalemia, hypomagnesemia).
• Risk factors for torsade include the following:
• • Congenital long QT syndrome
  • Acquired long QT syndrome (causes of which include medications and electrolyte disorders such as hypokalemia and hypomagnesemia)
  • Bradycardia
  • Female sex

Physical

The physical findings in torsade depend on the rate and duration of tachycardia and the degree of cerebral hypoperfusion.

• Findings include rapid pulse, low or normal blood pressure, or transient or prolonged loss of consciousness. This could be preceded by bradycardia or premature ventricular contractions (leading palpitations).
• Pallor and diaphoresis may be noted, especially with a sustained episode.
• Other physical signs depend on the etiology of torsade.

Causes

• Congenital long QT syndromes (adrenergic-dependent)
• • Jervell and Lange-Nielsen syndrome
  • Romano-Ward syndrome
• Acquired long QT syndromes
• • Antiarrhythmic drugs
    • Class 1A - Quinidine, disopyramide, procainamide
    • Class III - Sotalol, amiodarone (rare), ibutilide, dofetilide, almokalant
  • Histamine1-receptor antagonists - Terfenadine, astemizole
  • Cholinergic antagonists - Cisapride, organophosphates (pesticides)
  • Antibiotics - Erythromycin, clarithromycin, trimethoprim-sulfamethoxazole, clindamycin, pentamidine, amantadine, chloroquine, halofantrine
  • Antifungals - Ketoconazole, itraconazole
  • Diuretics - Indapamide
  • Psychotropic agents - Haloperidol, phenothiazines, thioridazine, trifluoperazine, sertindole, zimeldine, fluoxetine (possible)
  • Tricyclic and tetracyclic antidepressants
  • Antihypertensives - Bepridil, lidoflazine, prenylamine, ketanserin
  • Other drugs - Oral hypoglycemics, citrate (massive blood transfusions), vasopressin (possible), carbamazepine (possible), cocaine
  • Electrolyte abnormalities - Hypokalemia, hypomagnesemia, hypocalcemia
  • Endocrine disorders - Hypothyroidism, hyperparathyroidism, pheochromocytoma, hyperaldosteronism
  • Cardiac conditions - Myocardial ischemia, myocardial infarction, myocarditis, bradyarrhythmia, complete atrioventricular (AV) block
  • Intracranial disorders - Subarachnoid hemorrhage, thalamic hematoma, cerebrovascular accident, encephalitis, head injury
  • Nutritional disorders - Anorexia nervosa, starvation, liquid protein diets, gastroplasty and ileojejunal bypass, celiac disease

DIFFERENTIALS

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Other Problems to be Considered

Acquired long QT syndrome versus congenital long QT syndrome

Torsade should be differentiated from polymorphic ventricular tachycardia, monomorphic ventricular tachycardia, and supraventricular tachycardia with aberrant conduction.

WORKUP

Section 5 of 11  

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Lab Studies

• Electrolytes: Check for hypokalemia, hypomagnesemia, and hypocalcemia.
• Cardiac enzymes: Rule out myocardial ischemia, especially in patients without QT prolongation.

Imaging Studies

• Chest radiographs and echocardiography should be performed to rule out structural heart disease if any clinical suggestion is present.

Other Tests

• Electrocardiogram: Torsade is an electrocardiographic diagnosis, and obtaining an ECG is mandatory. The electrocardiographic features helpful in diagnosing torsade include its typical mode of onset and its morphology, as follows:
• • Patients have paroxysms of 5-20 beats, with a heart rate faster than 200 bpm; sustained episodes occasionally can be seen.
  • Progressive change in polarity of QRS about the isoelectric line occurs.
  • Complete 180° twist of QRS complexes in 10-12 beats is present.
  • Usually, a prolonged QT interval and pathological U waves are present, reflecting abnormal ventricular repolarization. The most consistent indicator of QT prolongation is a QT of 0.60 s or longer or a QTc (corrected for heart rate) of 0.45 s or longer.
  • A short-long-short sequence between the R-R interval occurs before the trigger response.
  • Patients may revert spontaneously or convert to a nonpolymorphic ventricular tachycardia or ventricular fibrillation.
  • Occasionally, T-wave alternans may be seen before torsade.
  • Torsade occurring in the setting of acquired long QT syndrome is preceded by pauses in almost all cases.
  • In congenital long QT syndrome (adrenergic-dependent), pause dependence is found in most of the adult cases while onset of torsade is not pause-dependent in children.
  • Failure to identify this rhythm may occur for various reasons. During very short runs of torsade, the typical twisting of the QRS complexes around the isoelectric line may not be apparent. Early events usually are short-lived.
  • In the case of a single-lead recording, the typical morphology of torsade may not be obvious.
  • The diagnosis of torsade should be considered in any patient with pause-dependent ventricular tachycardia, and ventricular bigeminy in a patient with long QT interval may be a sign of an impending torsade.
• Findings from electrophysiological studies usually are negative in torsade.
• Other tests should be ordered depending on the etiological factors being considered (see Causes).

TREATMENT

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Medical Care

Treatment can be divided into short-term and long-term management. Short-term management of torsade is the same in both acquired and congenital long QT syndrome except that beta1-adrenergic stimulation may be tried in the acquired form but is contraindicated in the congenital form.

• Short-term treatment
• • Defibrillation
  • • Although torsade frequently is self-terminating, it may degenerate into ventricular fibrillation, which requires direct current (DC) defibrillation.
    • In an otherwise stable patient, DC cardioversion is kept as a last resort because torsade is paroxysmal in nature and is characterized by its frequent recurrences following cardioversion.
  • Discontinuation of the offending agent
  • • Any offending agent should be withdrawn.
    • Predisposing conditions such as hypokalemia, hypomagnesemia, and bradycardia should be identified and corrected.
  • Suppression of early after depolarizations
  • • Magnesium is the drug of choice for suppressing EADs and terminating the arrhythmia. This is achieved by decreasing the influx of calcium, thus lowering the amplitude of EADs. Magnesium can be given at 1-2 g IV initially in 30-60 seconds, which then can be repeated in 5-15 minutes. Alternatively, a continuous infusion can be started at a rate of 3-10 mg/min. Magnesium is effective even in patients with normal magnesium levels.
    • Some authorities recommend supplemental potassium to increase the potassium concentration to high normal, which increases the efflux of potassium from myocardial cells, thus causing rapid repolarization.
    • Lidocaine usually has no effect in torsade. Occasionally, it can have an initial beneficial effect, but torsade recurs in all cases.
    • Mexiletine also may be helpful in suppressing torsade. In one study, it was used in patients with HIV who had acquired long QT interval and torsade. It effectively suppressed the torsade on a long-term basis.
    • Acceleration of the heart rate can be achieved by using beta1-adrenergic agonists such as isoproterenol or overdrive electrical pacing.
  • Isoproterenol
  • • This drug can be used in bradycardia-dependent torsade that usually is associated with acquired long QT syndrome (pause-dependent). It should be administered as a continuous IV infusion to keep the heart rate faster than 90 bpm.
    • Isoproterenol accelerates AV conduction and decreases the QT interval by increasing the heart rate and reducing temporal dispersion of repolarization. Beta-adrenergic agonists are contraindicated in the congenital form of long QT syndrome (adrenergic-dependent).
    • Because of precautions, contraindications, and adverse effects associated with its use, this drug is used as an interim agent until overdrive pacing can be started.
  • Temporary transvenous pacing
  • • Based on the fact that the QT interval shortens with a faster heart rate, pacing can be effective in terminating torsade. It is effective in both forms of the long QT syndrome because it facilitates the repolarizing potassium currents and prevents long pauses, suppressing EADs and decreasing the QT interval.
    • Atrial pacing is the preferred mode because it preserves the atrial contribution to ventricular filling.
    • In patients with AV block, ventricular pacing can be used to suppress torsade.
    • Pacing should be instituted at a rate of 90-110 bpm until the QT interval is normalized.
• Long-term treatment
• • Congenital long QT syndrome
  • • Beta-adrenergic antagonists at maximally treated doses are used as a first-line long-term therapy in congenital long QT syndrome. Propranolol is used most extensively, but other agents such as esmolol or nadolol also can be used. Beta-blockers are contraindicated in acquired cases because bradycardia produced by these agents can precipitate torsade. Beta-blockers should be avoided in those congenital cases in which bradycardia is a prominent feature.
    • Patients without syncope, ventricular tachyarrhythmia, or a family history of sudden cardiac death can be observed without starting any treatment.
    • Permanent pacing benefits patients who remain symptomatic despite receiving the maximally tolerated dose of beta-blockers and can be used adjunctively to beta-blockers. It decreases the QT interval by enhancing the repolarizing potassium currents and suppressing EADs.
    • High left thoracic sympathectomy, another antiadrenergic therapy, is effective in patients who remain refractory to beta-blockade and pacing. Accidental ablation of ocular efferent sympathetic nerves may result in Horner syndrome.
    • Implantable cardioverter-defibrillators (ICDs) are useful in rare instances when torsade recurs despite treatment with beta-blockers, pacing, and left thoracic sympathectomy. Beta-blockers should be used along with ICDs because shock can further precipitate torsade by adrenergic stimulation.
  • Acquired long QT syndrome
  • • Long-term treatment in acquired cases usually is not required because the QT interval returns to normal once the inciting factor or predisposing condition has been corrected.
    • Pacemaker implantation is effective in cases that are associated with heart block or bradycardia.
    • ICDs are indicated in cases that cannot be managed by avoidance of the offending agent.

Consultations

• Electrophysiologist
• Cardiologist
• Geneticist (in cases of familial or congenital long QT syndrome)

Diet

No special dietary restrictions are necessary unless warranted by a predisposing condition, eg, low-cholesterol and low-salt diet for patients with coronary artery disease.

Activity

Competitive sports are prohibited in patients with congenital long QT syndrome.

MEDICATION

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IV magnesium sulfate is the drug of choice for suppressing torsade in an acute setting; however, it is not used for long-term management. In the case of acquired long QT syndrome, the QT interval normalizes once the etiological agent has been reliably withheld, and the condition usually does not require long-term therapy. Beta-adrenergic antagonists are the drug of choice for the long-term treatment of congenital long QT syndrome and are contraindicated in the acquired form of the syndrome.

Drug Category: Electrolytes

Decreases amplitude of EADs by blocking inward calcium current and thus effectively terminating torsade. Effectively controls torsade on short-term basis.

Drug Category: Beta-adrenergic antagonists

In congenital long QT syndrome, events of torsade are triggered by some form of adrenergic stimulation that can be blocked effectively by beta-adrenergic antagonists. Propranolol is the most extensively used drug in these cases.

Drug Category: Antiarrhythmics

Mexiletine is structurally similar to lidocaine and is active orally. In one study in patients with HIV and acquired long QT interval, it effectively suppressed torsade on a long-term basis.

Drug Category: Beta-adrenergic agonists

Isoproterenol, which exerts its effect by stimulation of beta1 and beta2 receptors, is used in those acquired cases of torsade that are bradycardia-dependent. Accelerates AV conduction and reduces QT interval by reducing temporal dispersion repolarization.

FOLLOW-UP

Section 8 of 11  

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Further Inpatient Care

• Patients should be admitted to the intensive care or telemetry unit for continuous cardiac monitoring.

Further Outpatient Care

• Close follow-up is needed to optimize treatment, especially if patients are at high risk, eg, recurrent syncopal episodes, failure of medical therapy, or history of cardiac arrest.
• Patients should be asked about dizziness, syncopal episodes, and palpitations.
• Patients with ICDs should be monitored regularly to check the proper functioning of the device.
• Patients with acquired long QT syndrome should be educated regarding the potential offending agents. They should also be educated regarding the importance of avoiding commonly used drugs that can cause QT prolongation.

In/Out Patient Meds

• Beta-blockers - Propranolol used most commonly
• Mexiletine

Transfer

• Consider transfer to a facility at which the condition can be managed by an electrophysiologist, or at least a cardiologist, especially in patients with cardiac arrest.

Deterrence/Prevention

• Avoid offending drugs that prolong the QT interval either directly or by inhibiting the metabolism of a torsadogenic drug.
• Prevent predisposing conditions such as hypokalemia, hypomagnesemia, and hypocalcemia, especially in patients shown to have long QT interval.
• Screen families of patients with torsade for whom the cause for prolonged QT is suggested to be congenital.
• Educate patients and their families about the condition and predisposing factors.
• The role of routine electrocardiography to look for QT prolongation is unclear.
• If QT prolongation is found, it should be worked up and managed aggressively.

Complications

• Monomorphic ventricular tachycardia
• Ventricular fibrillation
• Sudden cardiac death

Prognosis

• In congenital long QT syndrome, the mortality rate for untreated patients is 50% in 10 years, which can be reduced to 3-4% with therapeutic intervention.
• In acquired long QT syndrome, the prognosis is excellent once the inciting factor has been identified and reliably withheld.

Patient Education

• Instruct patients to use medications only with the approval of a physician.
• Instruct patients to avoid competitive sports (in cases of congenital long QT syndrome).
• Close follow-up is needed because of a risk of sudden cardiac death.
• Offer emotional support; suggest attending a cardiac support group.
• Patients should be taught how to monitor their pulse and recognize adverse drug effects.
• Families should undergo training for basic life support.

MISCELLANEOUS

Section 9 of 11  

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Medical/Legal Pitfalls

• Failure to recognize heralding syncope
• Failure to screen family in cases of congenital long QT syndrome

MULTIMEDIA

Section 10 of 11  

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Media file 1:  Torsade de pointes. Marked QT prolongation in an asymptomatic patient on erythromycin. Patient also was found to be profoundly hypomagnesemic and hypokalemic.
	View Full Size Image
Media type:  ECG

Media file 2:  Torsade de pointes. Asymptomatic patient on erythromycin had marked QT prolongation on ECG findings. Patient was profoundly hypomagnesemic and hypokalemic. This shows an example of recurrent nonsustained torsade de pointes that occurred several hours after the ECG was performed. With discontinuation of the erythromycin and aggressive repletion of the magnesium and potassium, no further torsade de pointes occurred and the patient's QT interval returned to normal.
	View Full Size Image
Media type:  Rhythm Strip

REFERENCES

Section 11 of 11

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Article Last Updated: May 30, 2006