Episodes Of Torsade De Pointes Research Articles

A gender-independent proarrhythmic action of 17β-estradiol in anaesthetized rabbits

Women are at increased risk of having drug-induced arrhythmias such as torsade de pointes but less susceptible to arrhythmias associated with myocardial ischaemia. We have shown previously that 17beta-estradiol had greater antiarrhythmic activity in female rats than in male rats subject to myocardial ischaemia. The aim of this work was to investigate the effects of acute administration of 17beta-estradiol in both sexes in an established in vivo model of drug-induced arrhythmias. In alpha(1)-adrenoceptor-stimulated, pentobarbital-anaesthetized rabbits, 17beta-estradiol (100, 300 or 1000 ng/kg bolus followed by 10, 30 or 100 ng/kg/min infusion) tended to increase the incidence of torsade de pointes, induced by clofilium, in both sexes: from 50% in controls to 80%, 70% and 80% in females; from 40% in controls to 60%, 70% and 80% in males with increasing doses of 17beta-estradiol (n=10 per group). The total duration of all episodes of torsade de pointes was increased significantly by the highest dose of 17beta-estradiol compared to vehicle in both female and male rabbits: from 9+/-4 s to 93+/-26 s in females; from 26+/-14 s to 96+/-20 s in males. There were no baseline differences between the sexes in heart rate, QTc interval or epicardial monophasic action potential duration. The proarrhythmic effect of acute administration of 17beta-estradiol in the alpha(1)-adrenoceptor-stimulated anaesthetized rabbit model was independent of gender. This indicates that the underlying mechanism differs from that involved in the gender-selective reduction of ischaemia-induced arrhythmias by 17beta-estradiol.

Clarithromycin induced torsade de pointes

Clarithromycin is a commonly used macrolide antibiotic. It is known to cause QT prolongation. Medication induced QT prolongation is a major risk factor for the development of torsade de pointes. A 79-year-old lady presented with frequent episodes of torsade de pointes following commencement of clarithromycin. This was noted to be in association with a prolongation of the QT interval. Knowledge of medications which prolong the QT interval is important to minimize the risk of ventricular arrhythmias, which may lead to sudden death. This is essential in patients with a congenitally long QT interval.

Moxifloxacin and Torsade de Pointes

To report a case of torsade de pointes in a patient receiving moxifloxacin. An 87-year-old woman was admitted to the hospital for pneumonia, and antibiotic therapy with intravenous moxifloxacin 400 mg/day was initiated. The patient was noted to have significant QTc interval prolongation 2 hours after administration of moxifloxacin and developed torsade de pointes 8-10 hours after moxifloxacin administration. She was converted back to normal sinus rhythm after a precordial thump. Moxifloxacin was discontinued, and the woman's QTc interval subsequently returned to baseline. Torsade de pointes is a life-threatening arrhythmia that has previously been associated with the use of fluoroquinolones. Minimal information is available regarding the risk of torsade de pointes with moxifloxacin. According to the Naranjo probability scale, the episode in this case was probably related to administration of intravenous moxifloxacin. In patients with underlying risk factors for a prolonged QT interval, the use of moxifloxacin can lengthen the interval further and ultimately trigger episodes of torsade de pointes. Moxifloxacin administration in these patients therefore should be administered and monitored judiciously.

A case report of idiopathic giant cell myocarditis

Case Report A year old African American male was admitted to an outside hospital in July 007 with symptoms of severe heart failure that required implantation of a short-term left ventricular assist device (LVAD). He was subsequently transferred to our facility due to worsening left ventricular heart failure, episodes of Torsades de Pointes, and monomorphic ventricular tachycardia. His device was replaced with a longer-term LVAD and he was discharged home in October. Fortunately, he underwent successful orthotopic heart transplant in November 007.

Acquired long QT syndrome: Long-term electrocardiographic (Holter) recording of Torsades de Pointes ending in asystole: II

The Holter recording in an elderly female patient on Risperidone treatment who developed a longer than expected prolonged QT interval and associated Torsades de Pointes (TdP) at the onset of complete AV block is presented. The electrocardiographic manifestation of (likely) phase 2 early afterdepolarizations (EAD) as a trigger of TdP episodes; the TdP undulating or monomorphic morphologies as a counterpart of drifting or stationery scrolls, respectively, and the TdP final extinction leading to asystole and death are shown.

Two Cases of Acute Promyelocytic Leukemia Complicated by Torsade de Pointes during Arsenic Trioxide Therapy

We describe 2 patients with acute promyelocytic leukemia (APL) in whom torsade de pointes (TdP) developed during treatment with arsenic trioxide. Patient 1 was a 23-year-old woman with second-relapse APL. Ventricular premature beat bigeminy developed on day 27 of treatment, and episodes of TdP developed on day 28. Patient 2 was a 51-year-old woman with second-relapse APL who had cardiomyopathy due to prior anthracycline treatment. TdP developed on day 17 of treatment. Arsenic trioxide is known to cause electrocardiographic abnormalities, such as ventricular tachycardia and prolongation of QT interval. Patient 1 was given fluconazole as a concomitant drug. Patient 2 had cardiomyopathy and hypokalemia. Careful management is needed during arsenic trioxide therapy because this treatment prolongs the QT interval, possibly inducing episodes of TdP.

P5-111: Induction of torsades de pointes in association with epidural administration of bupivacaine

We report two cases of torsades de pointes (TdP) in association with epidural analgesia with bupivacaine (BUP). The first patient was a 36-year-old man who underwent surgical repair of an incarcerated hiatal hernia and gastric perforation, complicated by hepatic and renal impairment and mild electrolyte imbalance which was promptly corrected. During the postoperative course, shortly after administration of epidural BUP, he developed QRS widening and QT prolongation with recurrent episodes of polymorphic ventricular tachycardia and TdP.

RSD1235 blocks late INa and suppresses early afterdepolarizations and torsades de pointes induced by class III agents

RSD1235 is a novel antiarrhythmic drug with atria-selective electrophysiological actions on Na(+) and K(+) currents. The mechanism for its protection of ventricular repolarization was assessed by its action on Purkinje fibers, and by block of late sodium current active during repolarization. Further, RSD1235's ability to reverse the pro-arrhythmic actions of the class III agents dofetilide and clofilium was assessed in isolated Purkinje fibers and an in vivo model of torsades de pointes (TdP). Action potential and early after-depolarization (EAD) recordings were made from in situ and isolated rabbit Purkinje fibers at 37 degrees C using floating sharp microelectrodes; late I(Na) was recorded using a whole-cell patch clamp technique of Nav1.5 expressed in HEK cells at 22 degrees C; In vivo, anesthetized methoxamine-sensitized rabbits were used to test the ability of RSD1235 to suppress clofilium-induced TdP. RSD1235 (0.5-30 microM) had minor dose-dependent effects on action potential duration (APD) at 50% and 90% repolarization in Purkinje fibers, but pre-treatment significantly attenuated the APD-prolonging effects of dofetilide (300 nM). EADs induced by 300 nM dofetilide were terminated by 30 microM RSD1235 in all experiments (n=7). RSD1235 blocked a late component of Na current (I(Na)), which can produce inward currents contributing to EAD formation. RSD1235 pre-treatment (1 micromol/kg/min) or acute infusions prevented/terminated TdP induced by clofilium in 8 of 9 rabbits, and reduced the duration of TdP episodes from 71 +/- 23 s in control to 17 +/- 7 and 14 +/- 14 s at infusion rates of 0.3 and 1.0 micromol/kg/min, respectively (n = 9, p < 0.001). RSD1235 itself has minor actions on repolarization in Purkinje fibers, but can reverse the AP-prolonging actions of class III agents and terminate arrhythmias in a model of TdP. We suggest that these protective actions of RSD1235 may result, at least in part, from its ability to inhibit late I(Na) during action potential repolarization.

Palpitations in a Medical Intern

Palpitations in a Medical Intern

Classification and mechanism of initiation in patients with congenital long QT syndrome

To examine the initiating mode of Torsade de Pointes (TdP) in patients with congenital long QT syndrome (LQTS). We evaluated 111 episodes of TdP recorded on the electrocardiograms of 24 patients with congenital LQTS, and clarified the initiating mode, the three consecutive preceding RR intervals defined as C(2), C(1), and C(0), the timing of initiating premature ventricular contraction (PVC) and the cycle length (CL) of TdP. Three different initiating patterns were observed: (1) a "short-long-short" sequence (SLS) pattern (23 patients, 72 TdP, 65%) defined as one or more short-long cardiac cycles followed by an initiating short-coupled PVC (C(1)>C(2) and C(0)), (2) an "increased sinus rate" (ISR) pattern (8 patients, 28 TdP, 25%) defined as a gradual increase in sinus rate with or without T-wave alternans (C(2)>/=C(1)>/=C(0)), and (3) a "changed depolarization" (CD) pattern (5 patients, 11 TdP, 10%) defined as a sudden long-coupled PVC or fusion beat followed by short-coupled PVC. The C(0) was shorter in ISR than SLS and CD (mean C(0): 488 vs. 587 and 603 ms, respectively; P<0.05). Therefore, the initiating PVC appeared near the T-wave peak of the last beat before onset in ISR, while it occurred after the T-wave peak in SLS and CD. The CL of TdP was shorter in ISR than in SLS (256 vs. 295 ms, P<0.05). Our data show the existence of three predominant initiating modes of TdP in patients with congenital LQTS and suggests a differential mechanism of initiation of TdP for each mode.

Safety and efficacy of intravenously administered tedisamil for rapid conversion of recent-onset atrial fibrillation or atrial flutter

ObjectivesThe goal of the present study was to assess the efficacy and safety of intravenous tedisamil, a new antiarrhythmic compound, for conversion of recent-onset atrial fibrillation (AF) or atrial flutter (AFL) to normal sinus rhythm (NSR). BackgroundTedisamil is a novel antiarrhythmic drug with predominantly class III activity. Its efficacy and safety for conversion of recent onset AF or AFL to NSR is not known. MethodsThis was a multicenter, double-blind, randomized, placebo-controlled, sequential ascending dose-group trial. A total of 201 patients with symptomatic AF or AFL of 3 to 48 h duration were enrolled in a two-stage study. During stage 1, patients were randomized to receive tedisamil at 0.4 mg/kg body weight or matching placebo; during stage 2, patients received tedisamil at 0.6 mg/kg body weight or matching placebo. Treatments were given as single intravenous infusions. The primary study end point consisted of the percentage of patients converting to NSR for at least 60 s within 2.5 h. ResultsOf 175 patients representing the intention-to-treat sample, conversion to NSR was observed in 41% (25/61) of the tedisamil 0.4 mg/kg group, 51% (27 of 53) of the tedisamil 0.6 mg/kg group, and 7% (4/59) of the placebo group (p < 0.001 for both tedisamil groups vs. placebo). Average time to conversion was 35 min in patients receiving tedisamil. There were two instances of self-terminating ventricular tachycardia: one episode of torsade de pointes and one of monomorphic ventricular tachycardia, both in patients receiving 0.6 mg/kg tedisamil. ConclusionsTedisamil at dosages of 0.4 and 0.6 mg/kg was superior to placebo in converting AF or AFL. Tedisamil has a rapid onset of action leading to conversion within 30 to 40 min in the majority of responders.

Long QT syndrome and anaesthesia

Long QT syndrome (LQTS) is an arrhythmogenic cardiovascular disorder resulting from mutations in cardiac ion channels. LQTS is characterized by prolonged ventricular repolarization and frequently manifests itself as QT interval prolongation on the electrocardiogram (ECG). The age at presentation varies from in utero to adulthood. The majority of symptomatic events are related to physical activity and emotional stress. Although LQTS is characterized by recurrent syncope, cardiac arrest, and seizure-like episodes, only about 60% of patients are symptomatic at the time of diagnosis. 3 The clinical features of LQTS result from a peculiar episodic ventricular tachyarrhythmia called ‘torsade de pointes’. ‘Twisting of the points’ describes the typical sinusoidal twisting of the QRS axis around the isoelectric line of the ECG. Usually torsade de pointes start with a premature ventricular depolarization, followed by a compensatory pause. The next sinus beat often has a markedly prolonged QT interval and abnormal T wave. This is followed by a ventricular tachycardia that is characterized by variation in the QRS morphology, and a constantly changing R-R interval (Fig. 1). The ‘short-long-short’ cycle length sequence heralding torsade de pointes is a hallmark of LQTS. Commonly, the episode of torsade de pointes is self-terminating, producing a syncopal episode or pseudoseizure, secondary to the abrupt decrease in cerebral blood flow. The majority of episodes of sudden death in LQTS result from ventricular fibrillation triggered by torsade de pointes, although the mechanism of this deterioration is unknown. Traditionally, LQTS has been classified as either familial (inherited) or acquired. However, it is likely that many patients with previously labelled acquired LQTS carry a silent mutation in one of the genes responsible for congenital LQTS. 22 119 The evidence for this hypothesis has been gradually emerging over the past few years. It is important for anaesthetists to be aware of this concept, as it means that a much higher proportion of the general population may be affected by asymptomatic mutations in genes encoding cardiac ion channels than was thought previously. The prevalence of LQTS in developed countries may be as high as 1 per 1100‐3000 of the population. 32 119 About 30% of congenital LQTS carriers have an apparently normal phenotype, and thus a normal QT interval, and remain undiagnosed until an initiating event. 105 Fatal arrhythmias associated with primary electrical disease of the heart such as the Brugada and LQTS, probably account for 19% of sudden deaths in children between 1 and 13 yr of age, and 30% of sudden deaths that occur between 14 and 21 yr of age. 10 Furthermore, there is a strong association between prolonged corrected QT interval (QTc) in the first week of life and risk of sudden infant death syndrome. 86

Incidence and type of cardiac arrhythmias in critically ill patients: a single center experience in a medical-cardiological ICU.

To determine the frequency and types of significant, sustained arrhythmias in a mixed ICU. Prospective, observational study in a medical-cardiological-postoperative ICU at a university hospital. 133 consecutive patients with arrhythmias. All patients had continuous ECG monitoring and automatic arrhythmia detection. We assessed: (a) sustained (>30 s) tachyarrhythmias; (b) all tachyarrhythmias requiring therapy; (c) bradycardias of fewer than 40 beats/min or requiring intervention. There were 310 arrhythmia episodes: 278 tachyarrhythmias (108 narrow-QRS complex, 168 wide-QRS complex; 179 regular, 97 irregular) and 32 bradycardias. Of the 278 tachycardias in 54 patients, 135 (48.6%) were ventricular. There were 13 episodes of torsade de pointes (4.67%) in five patients. Of the 278 tachycardiac episodes 83 were atrial fibrillation (29.8%, 63 patients), 10 atrial flutter (3.6%, 8 patients), 21 supraventricular tachycardias (7.55%, 7 patients), and 2 ectopic junctional tachycardia (0.72%, 1 patient). The number of patients showing significant arrhythmias was comparable over the years (11-12/1996: 4/28 [14.3], 1997: 52/302 [17.2%], 1998: 55/286 [19.2%], 22/140 [15.7%] 1-7/1999). The ICU stay was significantly longer in arrhythmia patients than in 623 patients without arrhythmias (median 4 vs. 14 days), and there was a trend towards higher mortality (40/133, 30.8%, vs. 132/623, 21.2%, P=0.061, log-rank). Only one-fifth of patients in this mixed ICU had significant arrhythmias, taking a contemporary definition of arrhythmias. Ventricular tachycardia and atrial fibrillation were the most frequent arrhythmias.

Torsades de pointes in spontaneous intracranial haemorrhage successfully treated with isoproterenol

Acquired torsades de pointes (TDP) usually are due to electrolyte abnormalities, bradyarrhythmias, and drugs or toxins. Occasional reports have shown that TDP may be due to acute intracranial haemorrhage (IH), especially subarachnoid haemorrhage. Since a hyperadrenergic state is frequently observed in patients with IH, some authors suggest that a cause-and-effect relationship exists between IH and TDP due to the presence of cathecolamine-induced hypokalaemia, and therefore isoproterenol is not effective. We report a patient with spontaneous acute IH who had recurrent episodes of TDP, without simultaneous hypokalaemia, which were successfully treated with isoproterenol. In conclusion, normokalaemic patients with IH may have pause-dependent TDP responding to isoproterenol infusion. All physicians involved in the management of patients with IH or in the care of brain-death donors need to known the available treatment options for these ventricular tachyarrhythmias.

Torsades de pointes in spontaneous intracranial haemorrhage successfully treated with isoproterenol

Acquired torsades de pointes (TDP) usually are due to electrolyte abnormalities, bradyarrhythmias, and drugs or toxins. Occasional reports have shown that TDP may be due to acute intracranial haemorrhage (IH), especially subarachnoid haemorrhage. Since a hyperadrenergic state is frequently observed in patients with IH, some authors suggest that a cause-and-effect relationship exists between IH and TDP due to the presence of cathecolamine-induced hypokalaemia, and therefore isoproterenol is not effective. We report a patient with spontaneous acute IH who had recurrent episodes of TDP, without simultaneous hypokalaemia, which were successfully treated with isoproterenol. In conclusion, normokalaemic patients with IH may have pause-dependent TDP responding to isoproterenol infusion. All physicians involved in the management of patients with IH or in the care of brain-death donors need to known the available treatment options for these ventricular tachyarrhythmias.

Phase 2 early afterdepolarization as a trigger of polymorphic ventricular tachycardia in acquired long-QT syndrome : direct evidence from intracellular recordings in the intact left ventricular wall.

This study examined the role of phase 2 early afterdepolarization (EAD) in producing a trigger to initiate torsade de pointes (TdP) with QT prolongation induced by dl-sotalol and azimilide. The contribution of transmural dispersion of repolarization (TDR) to transmural propagation of EAD and the maintenance of TdP was also evaluated. Transmembrane action potentials from epicardium, midmyocardium, and endocardium were recorded simultaneously, together with a transmural ECG, in arterially perfused canine and rabbit left ventricular preparations. dl-Sotalol preferentially prolonged action potential duration (APD) in M cells dose-dependently (1 to 100 micromol/L), leading to QT prolongation and an increase in TDR. Azimilide, however, significantly prolonged APD and QT interval at concentrations from 0.1 to 10 micromol/L but shortened them at 30 micromol/L. Unlike dl-sotalol, azimilide (>3 micromol/L) increased epicardial APD markedly, causing a diminished TDR. Although both dl-sotalol and azimilide rarely induced EADs in canine left ventricles, they produced frequent EADs in rabbits, in which more pronounced QT prolongation was seen. An increase in TDR by dl-sotalol facilitated transmural propagation of EADs that initiated multiple episodes of spontaneous TdP in 3 of 6 rabbit left ventricles. Of note, although azimilide (3 to 10 micromol/L) increased APD more than dl-sotalol, its EADs often failed to propagate transmurally, probably because of a diminished TDR. This study provides the first direct evidence from intracellular action potential recordings that phase 2 EAD can be generated from intact ventricular wall and produce a trigger to initiate the onset of TdP under QT prolongation.

Chemical cardioversion of atrial fibrillation or flutter with ibutilide in patients receiving amiodarone therapy.

Ibutilide is a class III drug that is used for the cardioversion of atrial arrhythmias, but it can cause torsade de pointes. Amiodarone also prolongs the QT interval but rarely causes torsade de pointes. There are no studies in which the concomitant use of the 2 agents was examined. The purpose of the present study was to assess the efficacy and safety of cardioversion with combination therapy in patients with atrial fibrillation or flutter. The study included 70 patients who were treated with long-term oral amiodarone and were referred for elective cardioversion of atrial fibrillation (57 of 70, 81%) or flutter (13 of 70, 19%). Patients were taking amiodarone (153+/-259 days, mean+/-SD) and were administered 2 mg intravenous ibutilide. Left ventricular ejection fraction was measured with echocardiography. The QT intervals were measured on 12-lead ECG. Fifty-five patients (79%) had structural heart disease. Patients were in arrhythmia for 196+/-508 days before cardioversion, with a left ventricular ejection fraction of 50+/-11%. In patients with atrial fibrillation, 22 (39%) of 57 and 7 (54%) of 13 patients with flutter converted within 30 minutes of infusion. Thirty-nine patients who did not convert after ibutilide were treated with electrical cardioversion, and 35 (90%) of 39 patients were successfully converted. The QT intervals were further prolonged after ibutilide for the group from 371+/-61 to 479+/-92 ms (P:<0.001). There was 1 episode of nonsustained torsade de pointes (1 of 70, 1.4%) after ibutilide. The use of ibutilide converted 54% of patients with atrial flutter and 39% of patients with atrial fibrillation who were treated with long-term amiodarone. Despite QT-interval prolongation after ibutilide, only 1 episode of torsade de pointes occurred. Our observations suggest that combination therapy may be a useful cardioversion method for chronic atrial fibrillation or flutter.

Recurrent Torsades de Pointes After Sotalol Therapy for Symptomatic Paroxysmal Atrial Fibrillation in a Patient with End-Stage Renal Disease.

BACKGROUND: In recent years there has been ain increase in the use of class III antiarrhythmic drugs such as sotalol, amiodarone, and the so-called pure class III compound for the control of cardiac arrhythmias. It appears there has been a corresponding increase in the frequency of torsades de pointes (TdP). METHODS AND RESULTS: The case reported here, a patient on daily renal dialysis for end-stage renal disease, has important implications for class III agents, which are excreted largely by the kidneys. A relatively low dose of sotalol administered for the prevention of recurrences of atrial fabrillation, with a fast ventricular response producing angina, led to modest increases in the QT interval and moderate bradycardia. This culminated in the development of TdP, which deteriorated into ventricular fibrillation, from which the patient could be resuscitated with considerable difficulty. Dialysis after the occurrence of TdP led to further and striking prolongation of the QT interval associated with numerous episodes of TdP for several days before control was achieved. The atrial fibrillation and recurrences of TdP were eventually controlled with oral amiodarone. CONCLUSIONS: This case emphasizes that in the absence of significant renal function, use of sotalol may not be safe because drug accumulation may not be controlled adequately with renal dialysis. In view of this, in patients with end-stage renal disease, the use of sotalol for arrhythmia control appears contraindicated and alternative agents, the excretion of which does not occur by the renal route, should be used.

Time- and Rate-Dependent Alterations of the QT Interval Precede the Onset of Torsade de Pointes in Patients With Acquired QT Prolongation

Objectives. The purpose of this study was to determine whether the QT interval dynamics that precede torsade de pointes are consistent with the initiation of this arrhythmia by early afterdepolarization-induced triggered activity.Background. Early afterdepolarization-induced triggered activity has been suggested as an electrophysiologic mechanism for torsade de pointes. Consequently, the initiation of torsade de pointes should involve time- and rate-dependent alterations of ventricular repolarization similar to those known to modulate the development of early afterdepolarizations.Methods. RR and QT intervals were measured in digitized 24-h ambulatory electrocardiographic recordings obtained from seven patients with acquired prolongation of ventricular repolarization. Each patient had one or more episodes of torsade de pointes. The relation between RR and QT intervals was determined before, during and after multiple episodes of torsade de pointes.Results. In patients with multiple episodes of ventricular arrhythmias, the onset of the arrhythmias was associated with a critical prolongation of the QT interval. In some episodes, prolongation of the QT interval was associated with sudden prolongation of the sinus cycle length, whereas in other episodes, the QT interval prolonged progressively at a constant cycle length.Conclusions. The association between a critically prolonged QT interval and the onset of ventricular arrhythmias suggests that the initial complex of torsade de pointes is an early afterdepolarization-induced triggered response. However, prolongation of the QT interval itself was not sufficient to account for the initiation of torsade de pointes, suggesting that other, as yet unidentified factors are required.(J Am Coll Cardiol 1997;30:209–17)

Congenital Long-QT Syndrome

Figure 1. A 25-year-old woman who had had a single syncopal episode two years earlier was hospitalized after a two-minute episode of syncope during an argument with a police officer over a traffic ticket. A 12-lead electrocardiogram obtained on admission showed sinus rhythm, 52 beats per minute, with a markedly prolonged QT interval of 0.68 second. Twenty-four-hour Holter monitoring in the hospital revealed recurrent asymptomatic, mostly short, episodes of torsade de pointes. One such episode occurred during sleep and degenerated into ventricular fibrillation that lasted 11/2 minutes and terminated spontaneously. At that time, the patient wrote in her diary that . . .