Marked QT prolongation and ventricular tachycardia of a transient nature in young children with cardiomyopathy

Significant prolongation of the QT interval in pediatric patients with cardiomyopathy is rare. We report two cases of dilated myopathy with transient and dramatic QT prolongation. Both had associated ventricular arrhythmias, with one having torsade de pointes, and the other nonsustained ventricular tachycardia. Normalization of their QTc occurred as their ventricular function improved.     

QT Prolongation and Torsade de Pointes Ventricular Tachycardia Produced by Ketanserin

A 65-year-old man with arterial hypertension received oral treatment with Ketanserin, a new drug, during a period of five months. He developed marked QT interval prolongation and have several Stokes-Adams attacks. A Holter recording obtained during one of these episodes showed torsade de pointes ventricular tachycardia. The arrhythmias occurred during maximum QT interval prolongation, The correlation between Ketanserin and QT interval prolongation was evaluated by using several Holter studies during administration and withdrawal of the drug. The effect of Ketanserin on the QTc interval was analyzed retrospectively in six patients who had been taking the drug orally. Following a period of four to eight months, the QTc interval was prolonged by the drug (5 to 31%, mean 17%) in five patients. We conclude that torsade de pointes is a potential hazard of long-term treatment with Ketanserin.     

Amiodarone Therapy After Previous Sotalol-induced Torsade de Pointes: Analysis of AT Dispersion to Predict Proarrhythmia

BACKGROUND: Polymorphic ventricular tachycardia of the torsade de pointes type represents, potentially, the most dangerous side effect of antiarrhythmic drugs that prolong ventricular repolarization. Much effort has been devoted to the identification of the degree of drug-associated QT prolongation that might predict the occurrence of torsade de pointes. However, there is still no general agreement as to which level of QT prolongation might be the harbinger of torsade and which may simply represent the manifestation of the class III antiarrhythmic effect of a given compound. METHODS AND RESULTS: A 70-year-old woman who had survived an episode of cardiac arrest outside of a hospital was treated with dl-sotalol (320 mg/d). After 8 days of therapy, she developed two episodes of hemodynamically unstable torsade de pointes. Sotalol was withdrawn and after extensive diagnostic work, therapy with amiodarone therapy was comparable to that observed during sotalol exposure, the patient tolerated amiodarone and is now free of recurrent ventricular tachyarrhythmias over a follow-up period of 1 year. Analysis of QT dispersion in the surface electrocardiograph revealed a marked increase during sotalol therapy but not during amiodarone administration (77 vs 47 ms). During drug-free control, QT dispersion was 43 ms. CONCLUSIONS: These findings emphasize the potential usefulness of determination of QT dispersion from the surface ECG to assess disparity in ventricular recovery, which is known to favor the occurrence of torsade de pointes. These observations need to be corroborated in large prospective trials. Finally, this case report further emphasizes the low arrhythmogenic potential of amiodarone-an unexplained paradox, the understanding of which might provide insights for the development of newer antifibrillatory compounds.     

Ibutilide-induced long QT syndrome and torsade de pointes

Ibutilide is a class III antiarrhythmic agent used for the termination of atrial fibrillation and atrial flutter. It mainly affects membrane potassium currents and prolongs the cardiac action potential. This effect is reflected as QT interval prolongation on the surface electrocardiogram. Like other drugs that affect potassium currents, ibutilide is prone to induce a malignant ventricular tachycardia, torsade de pointes. We report four cases of torsade de pointes after administration of ibutilide for pharmacologic cardioversion of atrial fibrillation and atrial flutter; three of these cases required direct current cardioversion for termination of torsade de pointes. All four patients were female. We discuss the risk factors for development of ibutilide-induced torsade de pointes.     

Cocaine-induced channelopathies: emerging evidence on the multiple mechanisms of sudden death

Sudden death due to cocaine in the absence of myocardial infarction has been attributed to the precipitation of life-threatening arrhythmias not unlike that due to antiarrhythmic drugs. Cocaine is a slow on-off sodium blocker and a fast on-off potassium blocker. Effects on repolarization are biphasic: At low concentrations, cocaine delays ventricular recovery, whereas at higher levels, cocaine hastens it. Two distinct clinical profiles emerge from case reports of electrocardiographically documented life-threatening arrhythmias attributed to cocaine. The first is monomorphic slow ventricular tachycardia or idioventricular rhythm that occurs in overdose situations and appears to reflect excessive sodium channel block; it may respond to sodium bicarbonate. The second is torsade de pointes that occurs in recreational users who have underlying risks for this tachycardia (such as fully or partially expressed congenital long QT syndrome) and reflects potassium channel blockade. These clinical observations can be explained by recent findings regarding the electrophysiologic effects of cocaine. Other patterns of severe arrhythmias due to cocaine may yet emerge.     

Ciprofloxacin- and hypocalcemia-induced torsade de pointes triggered by hemodialysis

Torsade de pointes is a polymorphic form of ventricular tachycardia associated with prolongation of the QT interval, which may be either congenital or acquired. Etiologies for the acquired forms include drug effects, hypokalemia, hypomagnesemia, hypocalcemia, starvation, sick sinus syndrome, and atrioventricular block. We present a 76-year-old man with acute on chronic renal failure, hypocalcemia, on ciprofloxacin, and a prolonged QT interval with torsade de pointes triggered by hemodialysis. The QT prolongation was corrected by treating the hypocalcemia. Hypocalcemia and ciprofloxacin are known to independently cause prolonged QT interval and torsade de pointes; our case illustrates that dialysis can trigger torsade on a background of this risk factor combination.     

Torsade de Pointes and T-U Wave Alternans Associated with Arsenic Poisoning

Arsenic intoxication is a common form of heavy metal poisoning. Although arsenic-induced circulatory collapse, seizures, and syncope are well known, the potential for serious ventricular arrhythmias is less well recognized. Reported in this study are two cases of arsenic poisoning causing torsade de pointes. Furthermore, marked prolongation of the QT-U interval and the rarely observed phenomenon of T-U wave alternans are demonstrated. Thus, arsenic intoxication may be complicated by prolongation of the QT-U interval and torsade de pointes. T-U wave alternans occurs in the presence of a long QT-U interval and may be an electrocardiographic warning sign of torsade de pointes.     

Torsade de Pointes and Other Pause-Induced Ventricular Tachycardias: The Short-Long-Short Sequence and Early Afterdepolarizations

The early after depolarization, which is an interruption of repolarization, can evoke a second upstroke or a salvo of action potentials. It is suggested that the electrophysiological characteristics of the early after depolarization can produce a lengthening of the QT interval and that the second upstroke and salvo of activity that may follow, it can explain many features of torsade de pointes and of certain other ventricular tachycardias. The early after depolarization, torsade de pointes, and repetitive monomorphic idiopathic ventricular tachycardia are all induced hy bradycardia or by a preceding long RH interal. The R-on-T phenomenon is also discussed.     

Genetics of acquired long QT syndrome

The QT interval is the electrocardiographic manifestation of ventricular repolarization, is variable under physiologic conditions, and is measurably prolonged by many drugs. Rarely, however, individuals with normal base-line intervals may display exaggerated QT interval prolongation, and the potentially fatal polymorphic ventricular tachycardia torsade de pointes, with drugs or other environmental stressors such as heart block or heart failure. This review summarizes the molecular and cellular mechanisms underlying this acquired or drug-induced form of long QT syndrome, describes approaches to the analysis of a role for DNA variants in the mediation of individual susceptibility, and proposes that these concepts may be generalizable to common acquired arrhythmias.     

Torsade de pointes as a complication of brainstem encephalitis

A case of brainstem encephalitis complicated by torsade de pointes is described. The possible occurrence of ventricular arrhythmias may contribute to the mortality in this condition. We recommend the admission of patients with brainstem encephalitis to an intensivve care unit, for a period of electrocardiographic monitoring.

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Torsade de pointes as a complication of brainstem encephalitis

     

Haloperidol-induced torsade de pointes.

OBJECTIVE: To report a case of torsade de pointes related to the administration of high-dose intravenous haloperidol for the treatment of severe agitation. CASE SUMMARY: Reports in the literature of intravenous haloperidol-induced torsade de pointes are rare. We describe the case of a 41-year-old white woman with no predisposing factors who developed torsade de pointes 55 minutes after a dose of intravenous haloperidol 80 mg (total dosage 915 mg over 7 d). The results of the electrocardiogram were consistent with torsade de pointes and showed a prolonged QTc interval of 610 milliseconds. Intravenous magnesium sulfate 2 g/100 mL NaCl 0.9% was administered, which controlled the arrhythmia. The patient received one additional 80-mg haloperidol dose six hours after the arrhythmia-triggering dose, without reoccurrence of torsade de pointes. Haloperidol was then discontinued, and the patient had no further arrhythmias. CONCLUSIONS: Our case report and others from the literature suggest that intravenous haloperidol administration may prolong QT intervals in some patients, precipitating the potentially life-threatening arrhythmia torsade de pointes. Clinicians should be aware of haloperidol's potential to induce torsade de pointes, since it is used regularly for agitation and delirium in the critical care arena.     

Torsade de pointes caused by polypharmacy and substance abuse in a patient with human immunodeficiency virus

Drug-induced QT prolongation is a potentially dangerous adverse effect of some medication combinations. When QT prolongation progresses to torsade de pointes, life-threatening or fatal outcomes may result. A 57-year-old man with a history of human immunodeficiency syndrome on abacavir, nevirapine, tenofovir, voriconazole, and methadone presented to the emergency department with a chief complaint of new-onset seizures. The physical exam was unremarkable. The electrocardiogram demonstrated sinus bradycardia and a prolonged QT_c interval of 690 ms. In the emergency department, he had several episodes of torsade de pointes (TdP) and ventricular tachycardia that resolved spontaneously. These episodes were accompanied by an alteration in mentation and generalized twitching. Magnesium and amiodarone were effective in terminating the dysrhythmia. The patient had multiple risk factors for prolonged QT syndrome including human immunodeficiency virus infection, methadone therapy, and polypharmacy leading to potential drug interactions. Physicians must be aware of multidrug interactions potentiating QT prolongation and leading to torsade de pointes.     

Proarrhythmia

Proarrhythmia is defined as the aggravation of an existing arrhythmia or the development of a new arrhythmia secondary to antiarrhythmic drug. Proarrhythmic events include drug-induced bradyarrhythmias, atrial and ventricular proarrhythmias. New onset sustained or incessant ventricular tachycardia and torsade de pointes can be life threatening. This article reviews the incidence, aggravating factors, and treatment of proarrhythmia.     

Treatment of Life-threatening Ventricular Arrhythmias by a Combination of Antiarrhythmic Drugs and Right Ventricular Pacing

Thirteen patients with intractable ventricular arrhythmias were studied; they underwent long-term treatment by a combination of antiarrhythmic drugs and ventricular pacing. Eleven patients had a history of tachycardia and two had torsade de pointes; eleven of thirteen had had cardioversion and/or defibrillation. Prior to permanent pacemaker implantation, temporary pacing in the VVI mode was used in combination with one or more of the following drugs: amiodarone, aprindine, digitalis, metoprolol, mexiletine, procainamide, pindolol, propranolol, or quinidine. Various pacing rates were tried; when permanent pacing was instituted, a unipolar system which was at least rate-programmable was used. Right ventricular VVI pacing, combined with drug therapy, was successful in ten of thirteen patients. Five of the ten patients are alive and free of arrhythmias after 78, 72, 72, 54, and 11 months, respectively. Although five patients died (after 60, 48, 30, 24, and 9 months, respectively), none of the deaths were related to arrhythmias. We suggest that in patients with ventricular arrhythmias refractory to conventional treatment, a therapeutic trial of right ventricular VVI pacing in combination with a drug regimen be used.     

Challenges of diagnosis of long-QT syndrome in children

We describe the clinical and genetic characteristics of the family, in which the diagnosis of LQT1 had been made. The electrocardiogram (ECG) characteristics of this patient indicated the likelihood of LQTS1. Polymorphic ventricular extrasystolies and episodes of polymorphic non-sustained ventricular tachycardia were confirmed by Holter ECG monitoring. On the exertional electrocardiogram polymorphic ventricular tachycardia (torsade de pointes) was recorded. Direct sequencing of both DNA strands revealed the absence of mutations or polymorphisms in the KCNQ1, HERG, and SCN5A genes.     

Magnesium Therapy in Ventricular Arrhythmias

Magnesium (Mg) is the known activator of 300 enzymes which govern energy utilization, cell permeability, and ionic membrane currents in the cardiac conducting cells. This may explain the antiarrhythmic efficacy of Mg in specific clinical settings, despite its only modest electrophysiological effects. This review summarizes the effect of Mg administration in four clinical conditions: in digitalis toxicity; in drug-induced torsade de pointes; in patients with chronic diuretic therapy; and in acute myocardial infarction. Mg effectively abolished ventricular tachyarrhythmias associated with digitalis intoxication. This effect of Mg is related to the activation of sodium-potassium ATP-ase, which is inhibited by digitalis. Drug-induced torsade de pointes was promptly abolished by Mg sulfate in the clinical setting. Experimental studies showed that Mg suppresses the early afterdepolarizations and the triggered activity responsible for occurrence of the arrhythmia. In diuretic-treated hypertensives, potassium depletion has been associated with increased ventricular ectopy and sudden death. Mg has been found to be an important adjuvant for intracellular repletion of potassium in these patients. Several randomized, double-blind studies in patients with acute infarction showed that Mg administered on admission improved survival or reduced the incidence of complex ventricular arrhythmias. Thus, Mg should be employed as first-line therapy in digitalis intoxication and drug-related torsade de pointes, and should be considered an important adjuvant therapy in hypertensives treated with diuretics and patients with acute myocardial infarction.     

Suppression of Erythromycin-induced Early Afterdepolarizations and Torsade de Pointes Ventricular Tachycardia by Mexiletine

Erythromycin is a selective I_Kr-blocking, action potential duration (APD)-prolonging drug, which may induce early afterdepolarizations (EADs) and torsade de pointes ventricular tachycardia. The successful termination of an erythromycin-induced clinical torsades de pointes by the authors with mexiletine prompted them to investigate in vitro whether erythromycin is able to induce EADs in Purkinje fibers and, if so, whether EADs are suppressible or not by mexiletine. Electrically stimulated canine Purkinje fibers (n=9) were superfused with erythromycin (200 mg/l) and action potentials were recorded by an intracellular microelectrode technique. Erythromycin induced a pronounced prolongation of APD and the appearance of EADs in all Purkinje preparations (9/9). After the addition of mexiletine (10 mM), a marked shortening of APD and the disappearance of EADs (7/9) were observed. Mexiletine, an inhibitor of the tetrodotoxin-sensitive window Na+-current, may prevent IKr-blocking drug-induced torsade de pointes ventricular tachycardia by abolishing APD prolongation and EADs.     

Atypical proarrhythmia with dofetilide: monomorphic VT and exercise-induced torsade de pointes

Proarrhythmia with dofetilide has most typically taken the form of torsade de pointes (TdP) and generally occurs early with therapy, such that in-hospital initiation of dofetilide with 3 days of continuous electrocardiogram monitoring is recommended. This article reports two unusual variants of ventricular proarrhythmia with dofetilide: (1) nonsustained runs of monomorphic ventricular tachycardia shortly after taking the first dose of dofetilide, confirmed by rechallenge; and (2) TdP that followed the development of isolated ventricular premature beats during an exercise test in a patient with neither excessive QT prolongation on dofetilide nor any ectopy whatsoever during in-hospital telemetric monitoring but with significant QT interval prolongation after the postectopic pause. These cases demonstrate that clinicians must be alert to the appearance of proarrhythmia with dofetilide at times other than early during drug initiation if the electrophysiological milieu is altered during nonhospital activity and/or of a pattern other than TdP.     

Torsade de pointes

A case is described of torsade de pointes in a 41 year old woman with pre-existing QTc prolongation, potentially exacerbated by treatment with sotalol. Previous cardiac investigations had been normal and after a second episode of ventricular fibrillation the patient was referred for electrophysiological studies. The authors review the physiology, causes, and treatment of QTc prolongation and torsade de pointes.     

Flecainide‐Associated Bradycardia‐Dependent Torsade de Pointes: Another Potential Mechanism of Proarrhythmia

Although flecainide has a risk of proarrhythmia in patients with structural heart disease, its mechanism has been mainly ascribed to use‐dependency and a rapid ventricular response to organized atrial tachyarrhythmias or to ventricular tachycardia. We present a patient who experienced recurrent syncope due to bradycardia‐dependent torsade de pointes (TdP) associated with flecainide‐related bradycardia and QT prolongation. Bradycardia‐dependent TdP with QT prolongation can be considered as one of mechanisms of flecainide‐induced proarrhythmia.