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.     

Propafenone-Induced Torsade de Pointes: Cross-Reactivity with Quinidine

A 77-year-oid/emale with new onset atrial fibrillation occurring in the absence of structural heart disease developed torsade de pointes during therapy with quinidine bisulfate 500 mg orally every 8 hours. Ten days after quinidine therapy had been discontinued she developed torsade de pointes while receiving propafenone 300 mg orally every 8 hours. This case demonstrates that propafenone may be associated with torsade de pointes and suggests a cross-reactivity between this effect and prior occurrence of torsade de pointes on Class IA antiarrhythmic drug therapy.     

Amiodarone Induced Torsades de Pointes with Excessive QT Dispersion Following Quinidine Induced Polymorphic Ventricular Tachycardia

We report a case of amiodarone induced torsades de pointes (TdP) associated with increase QT dispersion in a patient with a history of quinidine induced TdP. An increase in QT dispersion of > 100% was noted on the 12 lead surface ECG postamiodarone therapy. In summary, amiodarone has a potential to induce TdP in patients with a previous history of quinidine induced TdP. QT dispersion could be a potential marker of TdP in these patients.     

抗菌药物诱导尖端扭转型室速16例及文献分析

目的 探讨抗菌药物诱导尖端扭转型室速(torsade de pointes,TDP)的规律及特点,为临床合理用药提供参考.方法 检索中国期刊全文数据库、维普、万方、中国生物医学文献数据库建库至2011年7月有关抗菌药物致TDP的病例报道,共16例,并进行分析.结果 16例患者中男3例,女13例;年龄17～88岁,平均5...     

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.     

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.     

Role of Early Afterdepolarization in Familial Long QTU Syndrome and Torsade de Pointes

Torsade de pointes (TdP) syncopal episodes were almost invariably precipitated by emotional stress or menstruation in a 17-year-old girl. V wave accentuation occurred during sinus rhythm without pauses in periods of heightened sympathetic tone. To examine the role of early afterdepolarization (EAD), monophasic action potentials were recorded during ventricular extrasystoles and TdP occurring spontaneously and induced by ventricular pacing. The effects of lidocaine, verapamil, propranolol, and epinephrine were assessed. Our data show that: (1) EAD plays a significant role in the genesis of familial long QTU syndrome and TdP; (2) rapid ventricular pacing causes postpause-dependent EADs, U waves, and TdP; and (3) EAD is enhanced by epinephrine infusion in the absence of pause, whereas EAD-triggered firing is inhibited by verapamil and propranolol but not by lidocaine.     

TU Alternans, Long QTU, and Torsade de Pointes: Clinical and Experimental Observations

T or U wave alternans in association with long QTU and torsade de pointes (TdP) is uncommon and its mechanism(s) is unknown. We studied three patients with TU alternans, long QTU, and TdP: patient 1 was a newborn with congenital long QTU; patient 2 had marked hypokalemia and hypomagnesemia; and patient 3 was receiving procainamide. In the three patients, TU alternans was tachycardia dependent and preceded the onset of TdP. In the patient on procainamide, TU alternans and TdP occurred at long cardiac cycles. In this patient, endocardial monophasic action potential (MAP) recordings showed that TU alternans was associated with alternation of the duration of the plateau. A deflection consistent with early afterdepolarization (EAD) arose at a constant time interval from phase 0 but alternated from high and low levels of phase 3. The first ectopic beat of TdP arose on the descending limb of the EAD. TU alternans was investigated by MAP recordings in six normal dogs, following the administration of anthopleurin-A (AP-A), a drug shown to delay sodium inactivation and to induce bradycardia dependent long QTU, EADs, and TdP. In two dogs TU alternans was associated with 2:1 recordings of EAD and nearly constant plateau duration. In three dogs, TU alternans was associated with EAD that occurred in consecutive beats at constant time intervals from phase 0, but alternated from high and low phase 3 because of alternation of the duration of the plateau. In one dog, alternation of EAD and plateau duration occurred. In 36 separate episodes of TdP that were analyzed in the six dogs, 32 were bradycardia dependent but four developed on abrupt shortening of the cardiac cycle associated with alternation of action potential duration. Our results suggest: (1) TU alternans may be due to 2:1 propagation of an EAD or to alternation of the recovery kinetics of a repolarization current; (2) The constant occurrence of EAD in relation to phase 0 in spite of alternation of plateau duration suggests an ionic mechanism synchronized to depolarization; (3) Tachycardia dependent TdP in clinical and experimental examples of long QTU seems to be characteristically associated with TU alternans. Dispersion of repolarization may underlie the increased ventricular electrical instability in these cases.     

Electrophysiologic parameters and predisposing factors in the generation of drug-induced Torsade de Pointes arrhythmias

When a new (cardiovascular) drug shows signs of QT interval prolongation on the ECG (delay in repolarization time), the regulatory agencies demand screening of its possible proarrhythmic potential before approving it for clinical practice. In this review, identified predisposing factors have been related to specific electrophysiological parameters, allowing quantification of their contribution to Torsade de Pointes arrhythmias. In addition, arrhythmogenic mechanisms involved in the initiation and perpetuation of drug-induced Torsade de Pointes are discussed.     

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.     

尖端扭转型室速40例临床分析

本文报道了汕头地区15年来收治的因原发心脏疾病和低血钾症所致尖端扭转型室速40例，并就其病因和治疗问题进行讨论，冠心病、长QT综合征所致尖端扭转型室速的发病机理及治疗上的某些进展，亦作了扼要的介绍。     

Sotalol Associated Torsades de Pointes Tachycardia in a 15-Month-Old Child: Successful Therapy with Magnesium Aspartate

Torsades de pointes (Tdp) is a form of ventricular tachycardia, and its occurrence in childhood is very rare. In adult patients treated with sotahl. Tdp has been reported to the occur with an incidence of 2%–4%. In children who are treated with sotalol. occurrence of Tdp has been reported in only a single case. A 15-month-old girl with Wolff-Parkinson-White syndrome developed recurrent syncopal attacks. She had been treated with sotalol 1.5 mg/kg daily since shortly after birth because of recurrent episodes of paroxysmal supraventricular tachycardia. ECG monitoring exhibited frequent Tdp tachycardia. Serum electrolyte levels were normal. Echocardiographic analysis excluded a structural heart defect and did not show any signs of myocardial infection. Sotalol treatment was stopped and an infusion with lidocaine was started. Despite this therapy the Tdp continued. Magnesium aspartate was then administered, which immediately stopped the Tdp. As no other reason was evident, Tdp in this child has to be judged as a proarrhythmia related to sotalol therapy.     

Sex differences in ventricular repolarization: from cardiac electrophysiology to Torsades de Pointes

A number of non-cardiovascular drugs have been withdrawn from clinical use due to unacceptable adverse cardiac side-effects involving drug-induced Torsades de Pointes (TdP)--a rare, life-threatening polymorphic ventricular tachycardia associated with prolongation of the action potential duration of ventricular myocytes and, hence, prolongation of the QT interval, of the electrocardiogram (ECG), which measures the total time for activation of the ventricles and their recovery to the resting state. Research has suggested that women are more prone to develop TdP than men during administration of medicines that share the potential to prolong the QT interval, with 65-75% of drug-induced TdP occurring in women. Clinical and experimental studies show that female sex demonstrate differences in the electrocardiographic pattern of ventricular repolarization in human and other animal species and is associated with a longer rate-corrected QT (QTc) interval at baseline than males. Reports of a similar propensity towards drug-induced TdP in both premenopausal and postmenopausal women support factors in addition to those of female sex hormones eliciting sex-based differences in ventricular repolarization. However, conflicting evidence suggests sex hormones may have a role in increasing the susceptibility of women or ultimately reducing the susceptibility of men to TdP. Cyclical variations in hormone levels during the menstrual cycle have been associated with an increased and reduced risk of TdP. In contradiction to this finding, the male sex hormone is thought to be beneficial. Modulation of the ventricular repolarization by testosterone may explain why the QTc interval shortens at puberty, and might account for the tendency towards an age-dependent reduction in the incidence of drug-induced TdP in men. Mechanisms underlying these differences are not fully understood but a case for the involvement of gonadal steroids is obviously strong. Therefore, further non-clinical/clinical investigations ought to be a necessary step to elucidate any sex differences in cardiac repolarization characteristics, QT interval prolongation and susceptibility to cardiac arrhythmias. This may have implications for the development of the safest medicinal products and for the clinical management of cardiac arrhythmias.     

Antiarrhythmic and Arrhythmogenic Actions of Varying Levels of Extracellular Magnesium: Possible Cellular Basis for the Differences in the Efficacy of magnesium and Lidocaine in Torsade de Pointes

BACKGROUND: In recent years, there has been an increasing use of antiarrhythmic drugs that act predominantly by prolonging myocardial repolarization. An inevitable electrophysiologic consequence of these drugs is the development of torsade de pointes as a proarrhythmic reaction. Both intravenous lidocaine and magnesium sulphate have been used in the acute control of such a proarrhythmia. Their electrophysiologic mechanisms in this setting are not well defined. METHODS AND RESULTS: Using the standard microelectrode techniques, the effects of magnesium (Mg) and lidocaine on action potential duration (APD), and on barium-induced spontaneous action potentials, were studied in canine Purkinje fiber preparations. The objective was to clarify the direct and indirect effects of magnesium on triggered activities due to early afterdepolarizations. Superfusion in media with 0.1 mM Mg and 2.5 mM K produced more pronounced increases in APD measured at -20mV repolarization time [APD(20)] than those in a solution with 5 mM K. This effect was further enhanced at lower stimulation frequencies. The striking prolongation of APD(20) by solutions with low potassium concentrations diminished as the Mg concentration was increased. In solutions with 2.5 mM K, Mg produced concentration-dependent decreases in APD(20). This effect was greater at lower stimulation frequencies. Lidocaine at 4.0 x 10(_5) M produced a marked shortening of the APD in the entire firing frequency of the abnormal automaticity in a concentration-dependent manner. With 10 mM Mg, such action potentials appeared only sporadically. Magnesium also decreased the amplitude and the maximum upstroke velocity of these action potentials. In contrast, lidocaine at 4.0 x 10(-5) M exhibited no significant effects on action potentials due to barium-induced abnormal automaticity, or on additional depolarizations developing from the repolarization phase of these action potentials. CONCLUSIONS: The data indicate that (i) hypomagnesemia may be arrhythmogenic when combined with hypokalemia and bradycardia leading to a prolongation of the plateau phase of the action potential, (ii) magnesium administration may suppress triggered activities mainly by a direct inhibition of the development of triggered potentials, and (iii) lidocaine may suppress triggered potentials only indirectly by preventing the development of early afterdepolarizations due to the shortening effect on the APD. These findings are consistent with the clinical observation of a high incidence of torsade de pointes in the setting of hypokalemia and hypomagnesemia introduced by a chronic diuretic therapy. They are also consistent with the marked effectiveness of intravenous Mg relative to the inconsistent clinical effects of lidocaine in controlling torsade de pointes.     

心脏术后心律失常应用胺碘酮针的疗效观察

【目的】观察胺碘酮针剂治疗心脏手术后合并心律失常的疗效及安全性。【方法】回顾分析80例风湿性心脏病和先天性心脏病术后合并阵发性室性心动过速、室性早搏或房颤的的患者,以胺碘酮针剂2~3mg/kg加入5%葡萄糖溶液10~20 ml,缓慢静脉注射,效果不明显者于30 min后再次静注1 mg/kg剂量,而后按5~10 mg/(kg.d)持续静脉滴注1~5 d,监测血压和心率的变化。【结果】胺碘酮治疗后有效率为95%,能较好的控制心率,且对血压影响不明显。【结论】胺碘酮针剂治疗心脏手术后合并阵发性室性心动过速或室性早搏、快速性房颤的疗效较好。     

麻醉前后的QT离散度分析

目的 :探讨麻醉前后QT离散度 (QTd)的变化及其临床意义。方法 :检测并计算出 5 5例手术病人麻醉前后的QT、QTc离散度 ,其中 12例为全身麻醉 ,4 3例为连硬麻醉。结果 :麻醉后病人的QTd、QTcd大于麻醉前 ,差异非常显著 (P <0 .0 1) ,全身麻醉后QTd、QTcd增大较连硬麻醉后更为明显 (P分别 <0 .0 5和 <0 .0 1)。结论 :麻醉可增大心室肌的复极离散度 ,可能与麻醉过程中心律失常的发生率增加相关 ,麻醉过程中应加强心脏监护 ,确保麻醉安全。     

Repetitive Supraventricular Tachycardia: Clinical Manifestations and Response to Therapy with Amiodarone

Repetitive supraventricular tachycardia is an uncommon arrhythmia which usually occurs in patients free of structural heart disease. It is characterized by incessant short salvos of supraventricular tachycardia separated by only one or two normal sinus beats. Therapy with conventional antiarrhythmic drugs is usually ineffective. This report describes three patients with repetitive supraventricular tachycardia in whom evidence for associated sinus node dysfunction was observed. Amiodarone therapy, with ventricular pacing in two patients, has provided effective control of this arrhythmia in all three patients.     

Fast Fourier Transform Analysis of Ventricular Fibrillation Intervals to Predict Ventricular Refractoriness and Its Spatial Dispersion

A technique of fast Fourier transform analysis has been used to derive mean ventricular fibrillation (VF) intervals, and to confirm that these VF intervals predict ventricular refractory periods. Twenty episodes of VF were induced by a rapid ventricular pacing in 12 sheep. VF activations in a 10-second period were simultaneously acquired from 64 epicardial sites with an electrode sock. The VF electrograms were analyzed by a fast Fourier transform analysis. The dominant peak frequency of the VF spectrum in each epicardial site was converted into milliseconds and served as a mean VF interval. The dominant peak frequency of VF electrograms ranged from 8.1 to 11.5 Hz, and the corresponding mean VF intervals were 87 to 124 ms. In five sheep, the mean VF intervals and the effective refractory periods were determined by the extrastimulus technique obtained from 29 epicardial sites. There was a very good correlation between the two parameters when the effective refractory periods were determined at a basic cycle length of 300 ms (r = 0.89, P < 0.001) and 400 ms (r = 0.87, P < 0.001), respectively. VF was induced twice in eight sheep. The maximum difference in the mean VF intervals between the two VF episodes in the same sheep was 3 ms (P > 0.05). In conclusion, mean VF intervals determined by the fast Fourier transform analysis have a good reproducibility and a good correlation with ventricular refractory periods measured by the classic extrastimulus technique. The mean VF intervals could serve as an index of ventricular refractoriness.