Torsades de pointes is a clinical condition involving a particular form of irregular heart rhythm which leads to sudden cardiac death. It is a polymorphic ventricular tachycardia characterized by a progressive shift in amplitude and torsade formation along the isoelectric line (baseline) in the QRS complexes. Torsade is a French word, used for twisting in the account. Dessertenne mentioned it in the year 1966 [1]. It is connected to a prolonged QT interval, which may be congenital or acquired. It can follow extreme bradycardia, and accompanying ventricular fibrillation has been noted [4,5]. The arrhythmia can range from 3 beats of unsustained ventricular tachycardia to > 100 beats in length. The intervals between QRS complex differ, and tachycardia levels are normally between 200 – 250 beats/min (range: 150 – 300 beats/min) [6]

Prolonged repolarization occurs in Torsades de pointes, and may be due to problems with electrolytes, bradycardia, congenital syndromes or the use of other drugs. The Extension of Repolarization can result in the subsequent activation of a current of inward Depolarization, known as an early post-Depolarization [2,3]. Because of the dispersion of refractory times, re-entry is possible because of M Cells (found in the middle myocardial layer) display a longer repolarization process in response to potassium blockage than any other cell. This, in turn, creates a functional refractory zone in the mid-layer of the myocardial [3].

Mutations in five genes, including KCNQ1, HERG, SCN-, KCNE1 and KCNE2 cause congenital long QT syndrome (LQT). Mutations in the genes KCNQ1 and KCNE1 are responsible for defects in IKs, the gradually activating portion of the delayed potassium rectifier present, while mutations in the genes HERG and KCNE2 are responsible for defects in IKr, which is quickly activating portion of the delayed potassium rectifier present. SCN-gene mutations enhance the INa, a sodium channel, function [7]. This, in turn, creates a functional refractory zone in the mid-layer of the myocardial [3]. The Purkinje network is the predominant position where the activated beats caused early afterdepolarization to emerge. The focal activated beats induced early afterdepolarization infringe the underlying substratum of inhomogeneous repolarization and initiate a serial reentry process resulting in the initiation and maintenance of torsade points [8].

Major causes of long QT syndrome and torsade de pointes
Congenital long QT syndrome
Acquired long QT syndrome
Pharmacological agents
Electrolyte abnormalities
Sinus node dysfunction
High grade atrioventricular block
Myocardial injury and ischemia
Starvation
Anorexia
Liquid protein diets
Human immunodeficiency virus (HIV)
Intracranial disease
Cocaine abuse
Organophosphorous poisoning
Stress
Major causes of long QT syndrome and torsade de pointes
CategoryDrugs
Anti=arrythmicDisopyramide, procainamide, n-acetyl-procainamide, quinidine, beperdil, mexiletine, propafenone, flecainide, amiodarone, bretylium, sotalol, ibutilide, dofetilide, azimilide, aprindine, ajmaline, almokalant, mibefradil, clofilium, sematilide
Anti-microbialsErythromycin, clarithromycin, azithromycin, ampicillin, levofloxacin, moxifloxacin, sparfloxacin, gatifloxacin, grepafloxacin, trimethoprim-sulfamethoxazole, troleandomycin, Pentamidine, quinine, foscarnet, fluconazole, itraconazole, ketoconazole, chloroquine, halofantrine, mefloquine, amantadine, spiramycin
Anti-histaminesAstemizole, diphenhydramine, terfenadine, ebastine, hydroxyzine
Anti-depressantDoxepin, fluoxetine, desipramine, imipramine, clomipramine, paroxetine, sertraline, venlafaxine, citalopram, ketanserin
Anti-psychotics Chlorpromazine, prochlorperazine, trifluoperazine, fluphenazine, felbamate, haloperidol, droperidol, mesoridazine, pimozide, quetiapine, risperidone, thioridazine, ziprasidone, lithium, chloral hydrate, pericycline, sertindole, sultopride, zimeldine, maprotiline  
Anti-convulsantsFelbamate, fosphenytoin
Anti-anginalsvasodilators, Bepridil, lipoflazine, prenylamine, intracoronary,papaverine
Anti-hypertensivesIsradipine, nicardipine, moexipril/hydrochlorthiazide
Anti-cancer drugsArsenic trioxide, tamoxifen
Anti-lipidemicProbucol
Anti-migraine agentsSumatriptan, zolmitriptan, naratriptan  
DiureticsIndapamide thiazide, furosemide
EndocrineOctreotide
Gastrointestinal stimulantsCisapride, metoclopramide, domperidone, erythromycin
OthersArsenic trioxide, tizanidine, tacrolimus, salmeterol, levomethadyl, pinacidil, cromakalin, aconitine, veratridine, batrachotoxin, anthopleurin A, ketanserin, vincamine, terodiline, budipine, cesium chloride, tiapride, levomethadyl acetate, cocaine, organophosphorus compounds.  
Drugs reported to prolong QT interval and/or induce torsade de pointes

The torsade de pointes caused by the medication is a fairly rare occurrence, but with certain drugs, its incidence can be as high as 2 – 3% [9]. Females are two to three times more likely to develop torsade de pointes induced by drugs[10]. Older people are more likely to torsade compared with younger people. Genetically, the incidence rate of torsade de pointes is 75%. In addition to drugs, there is an increased risk of torsade de pointes with hypokalaemia, hypomagnesemia, hypocalcemia, severe bradycardia, high-grade atrioventricular block and impaired ventricular function [11, 12].

PATHOPHYSIOLOGY

The action potential of cardiac muscles can be divided into five phases which are as follows:
Phase 0: The opening of sodium channels, resulting in the entry of Na+ into the cells leading to the depolarization of cardiac muscles.
Phase 1: Closing of sodium channels that prevent depolarization. Potassium channels open, leading to K+ out of the cells at an outward current.
Phase 2: Potassium channels remain open, and the calcium channels are now open, leading to a plateau state.
Phase 3: Calcium channels close, but potassium channels are still open, and that remains until the cells achieve normal polarization.
Phase 4: Exciting stimuli cause slight depolarization in the cells resulting in increased sodium channel permeability causing the opening of sodium channels.

DIAGNOSIS

Symptoms typically begin in preteen to early adolescence but can appear as early as the first day of life or as late as 40–50 years of age [13,14]. Usage of QT-prolonging medications or condition such as hypokalemia contributes to the creation of symptomatic events in congenital LQT patients. The signature feature of torsades de pointes in an electrocardiogram rhythm stripe is the polymorphic ventricular tachycardia associated with QT interval prolongation. This leads to ventricular fibrillation if untreated. There is a brief, pre-initiating RR interval due to a premature ventricular beat, followed by a long initiating period following the premature ventricular beat that results from the compensatory pause [15].

MANAGEMENT

Short-term treatment

TypePharmacologicalNon pharmacological
CongenitalMagnesium sulfatePermanent Cardiac pacemaker
 B-BlockersCardiothoracic sympathectomy
 Mexiletinea 
  Implantable cardioverter defibrillator
AcquiredMagnesium SulfateRemoval of the cause
 IsoproterenolTemporary Cardiac Pacing
 Atropine 
 Lidocaine 
 Phenytoin 
 Sodium Bicarbonate 
Summary of the treatment of torsade de pointes and long QT syndrome

The variations in pathophysiology between the congenital and acquired forms of torsade de pointes contribute to some significant differences in treatment [16]. Immediate intravenous magnesium sulfate administration is suggested as the first-line therapy for long QT-interval associated ventricular ectopic beats and torsade de pointes [17].

Long-term treatment

Congenital long QT syndrome:

Beta-adrenergic blockers are used in long-term, congenital QT syndrome as first-line therapy. Propranolol was the drug used the most commonly. In acquired cases, beta-blockers are contraindicated because of the bradycardia induced by those agents results in torsade growth. High left thoracic sympathectomy is successful in patients with beta-blockade and pacing remaining refractory. Implantable cardioverter-defibrillators (ICDs) are effective in extreme situations where after both of these therapies torsades still occur. Beta-blockers should be used along with ICDs because through adrenergic activation, the shock will further precipitate torsades [18]

Acquired long QT syndrome:

In acquired cases, long-term treatment is typically not needed, as the QT interval returns to normal once the predisposing factor has been corrected. Pacemaker implantation is successful for heart block or bradycardia related cases. In cases which can not be controlled by avoiding any particular precipitating factor, the ICDs are given [18].

INVESTIGATIONS

ECG: 5-20 beat paroxysms, with a heart rate above 200 beats per minute. Sustained episodes are seen from time to time. The progressive shift of QRS polarity along the isoelectric line occurs in 10-12 beats with an absolute 180 ° twist of QRS complexes.
A prolonged QT interval and U-waves are usually present [19].

Electrolytes: Hypokalaemia, Hypomagnesaemia and Hypocalcaemia.

CLINICAL PRESENTATION

Stress, fear or physical exertion can cause episodes of Torsades in patients with long congenital QT syndromes. Torsade patients typically experience repeated episodes of palpitations, dizziness and syncope[5]. The onset of the first episode can result in sudden cardiac death. Nausea, pallor, cold sweats, shortness of breath and chest pain may occur. A history of congenital deafness or sudden death in a family may indicate a long QT syndrome. Physical findings depend on the tachycardia rate and duration, and the degree of hypoperfusion in the brain. Rapid heartbeat, low or high blood pressure, and intermittent or prolonged loss of consciousness are all observations. Other physical signs depend on the cause – eg, features of a congenital disorder [20].

PROGNOSIS

Patients can spontaneously revert or convert to non-polymorphic tachycardia or ventricular fibrillation. Torsades is a life-threatening arrhythmia and can present in patients with structurally normal hearts as sudden cardiac death. The prognosis is excellent for acquired long QT syndrome once any precipitating factor has been removed [18].

PREVENTION

Avoid offending drugs which extend the QT interval. Prevent predisposing conditions such as hypokalemia, hypomagnesaemia and hypocalcaemia, especially in patients with documented long QT intervals. Screen families of torsade patients for whom it is believed the cause of prolonged QT is congenital [18].

CONCLUSION

In this report, clinical overview of torsade de pointes was represented. It was found that Torsade de pointes occurs mainly because of two factors, congenital and acquired. Congenital causes occur in individuals with genetic mutations in genes that control the expression of potassium and sodium channels and Acquired causes are many but predominantly drugs cause them by blockade of potassium channels. Drugs such as Quinidine, Solatolol, Dofetilide and Ibutilide are potential drugs to cause fatal Torsade de Pointes. Based on the findings it is recommended that drugs such as Magnesium Sulfate, Beta-blockers, Mexiletinea are mainly used for the treatment of Congenital Causes and drugs such as Magnesium Sulfate, Isoproterenol, Atropine, Lidocaine, Phenytoin, Sodium Bicarbonate are mainly used for the treatment of Acquired Causes. An electrocardiograph is taken and the levels of potassium and sodium are evaluated by which the occurrence of Torsade de pointes can be known.

REFERENCES

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2. Kaye AD, Volpi-Abadie J, Bensler JM, et al; QT interval abnormalities: risk factors and perioperative management in long QT syndromes and Torsades de Pointes. J Anesth. 2013 Aug27(4):575-87. DOI: 10.1007/s00540-013-1564-1. Epub 2013 Feb 15..

3. Yap, Yee Guan; Camm, A John (2017-01-17). “Drug-induced QT prolongation and torsades de pointes”. Heart. 89 (11): 1363–1372. ISSN 1355-6037. PMC 1767957 Freely accessible. PMID 14594906.

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8. El-Sherif N, Caref EB, Yin H, Restivo M. The electrophysiological mechanism of ventricular tachyarrhythmias in the long QT syndrome: tridimensional mapping of activation and recovery patterns. Circ Res 1996;79:474 – 92.

9. Ebert SN, Liu XK, Woosley RL. Female gender as a risk factor for drug-induced cardiac arrhythmias: evaluation of clinical and experimental evidence. J Women’s Health 1998;7:547 – 57.

10. Makkar RR, Fromm BS, Steinman RT, Meissner MD, Lehmann MH. Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs. JAMA 1993;270:2590 – 7.

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13. Zareba W, Moss AJ, Schwartz PJ, et al. Influence of genotype on the clinical course of the long-QT syndrome: International Long-QT Syndrome Registry Research Group. N Engl J Med 1998;339:960 – 5.

14. Vincent GM, Timothy K, Leppert M, Keating M. The spectrum of symptoms and QT interval in carriers of the gene for the long QT syndrome. N Engl J Med 1992;327:846 – 52.

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16. Khan IA. Long-QT syndrome: diagnosis and management. Am Heart J 2002;143:7 – 14.

17. Tzivoni D, Banai S, Schuger C. Treatment of torsades de pointes with magnesium sulfate. Circulation 1988;77:392.

18. Drew BJ, Ackerman MJ, Funk M, et al; Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. J Am Coll Cardiol. 2010 Mar 255(9):934-47. DOI: 10.1016/j.jacc.2010.01.001.

19. ECG Library.

20. Brignole M; Diagnosis and treatment of syncope. Heart. 2007 Jan 93(1):130-6.

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