Clinical,electrocardiographic and follow-up observations in patients having ventricular fibrillation during holter monitoring: Role of quinidine therapy

Ventricular fibrillation occurred during Holter electrocardiographic monitoring in 5 of 3,307 consecutive patients. All five patients had Holter studies for evaluation of antiarrhythmic drug therapy; their ages ranged from 51 to 65 years. No patient had acute myocardlal infarction; all had congestive heart failure and severe left ventricular dysfunction. One patient had ischemic and four had nonischemic cardiomyopathy. All patients had recently begun treatment with oral quinidine and had plasma quinidine levels of 1.24 to 5.18 μg/ml. The Holter monitoring revealed that all had a long Q-T interval and that ventricular fibrillation began during frequent ventricular premature beats and was immediately preceded by ventricular tachycardia of the torsade de pointes type. The coupling interval of the ventricular premature beats initiating torsade de pointes was late (440 to 720 ms) and followed long preceding cycles (840 to 1920 ms). Ventricular fibrillation resolved spontaneously in two patients, but two of the remaining three patients died despite attempted cardiopulmonary resuscitation.It is concluded that (1) left ventricular dysfunction, chronic ventricular arrhythmias and initiation of quinidine therapy were the common findings in these patients; (2) a long Q-T interval, late coupled ventricular premature beats and long preceding cycles facilitate initiation of ventricular fibrillation in quinidine-treated patients; and (3) direct on-line monitoring should be utilized in the management of these patients.     

Torsade de pointes: the long-short initiating sequence and other clinical features: observations in 32 patients

The clinical setting, precipitating factors, electrocardiographic features and response to treatment of 32 patients with torsade de pointes were reviewed. Thirty-one patients had underlying cardiac disease and 30 patients had a previous underlying cardiac arrhythmia. Antiarrhythmic medications, often in association with electrolyte abnormalities (such as hypokalemia and hypomagnesemia) were the most common precipitating factors. In 22 of 26 patients, the serum drug levels of the antiarrhythmic agents were found to be within the therapeutic range. However, before the administration of agents known to prolong the QT interval, 20 of the 32 patients had, either alone or in combination, baseline prolongation of the QT interval, hypokalemia or hypomagnesemia. All patients had QTc interval prolongation (mean 0.59 second) immediately before the development of torsade de pointes. Marked lability of T wave morphology was frequently noted. Cardiac pacing was the only consistently effective mode of therapy. A characteristic long-short ventricular cycle length as the initiating sequence was found in 41 of 44 episodes of torsade de pointes. Reported data support the high frequency of this electrocardiographic feature of torsade de pointes in which its onset could be analyzed. It is suggested that this electrocardiographic characteristic will aid in both establishing the diagnosis of torsade de pointes and distinguishing it from other polymorphic forms of ventricular tachycardia.     

Torsades de Pointes as a Cause of Sudden Death in a Patient with Aortic Stenosis and Atrial Fibrillation

The occurrence of sudden cardiac death during Holter monitoring in patients with aortic stenosis has been reported previously. In the majority of the reported cases, the cause of death was a malignant ventricular tachyarrhythmia. The presence of a strong association between frequency and complexity of ventricular arrhythmias and sudden death in patients with aortic stenosis has been proposed. We report the case of a 77‐year‐old woman with aortic stenosis and atrial fibrillation who had an episode of torsades de pointes that degenerated into ventricular fibrillation during Holter monitoring. A short–long–short sequence, but not increased ventricular ectopics, precipitated torsades de pointes and sudden death in this case which is strongly indicative of triggered activity as the underlying mechanism of the lethal arrhythmia.     

Spontaneous sequences of onset of torsade de pointes in patients with acquired prolonged repolarization: Quantitative analysis of Holter recordings

Objectives. This study investigated the cycle length changes preceding the spontaneous onset of torsade de pointes in patients with acquired prolonged ventricular repolarization.

Background. Torsade de pointes is a polymorphic ventricular tachycardia generally associated with prolonged ventricular repolarization. Because torsade de pointes is not inducible by programmed electrical stimulation, quantitative analysis of Holter recordings of spontaneous episodes may clarify the mechanisms favoring the onset of torsade de pointes in actual clinical conditions.

Methods. The digitized Holter recordings of 12 patients were analyzed by a computerized Holter system (ATREC). All arrhythmias were grouped according to three classes: 1) isolated premature ventricular beats (n = 47,147, mean/patient [±SD] 3,929 ± 11,571); 2) salvos of 2 to 4 consecutive beats (n = 2,003, mean/patient 167 ± 359); 3) torsade de pointes ≥5 beats (n = 105, mean/patient 9 ± 11). For each patient and class of arrhythmias, six variables were computed from the 10 min and the 10 cycles preceding the event onset.

Results. A significant heart rate increase in the last minute (p < 0.01) and typical oscillatory short-long-short cycle length sequences preceded the onset of arrhythmias, with greater oscillation preceding torsade de pointes than salvos and premature ventricular beats. The cycle lengths preceding the onset were highly correlated with the class of arrhythmias (r = 0.65, p < 0.005) and allowed the correct classification of 69% of events by discriminant analysis (p < 0.0001). A significant negative correlation was observed between the duration of torsade de pointes and the mean length of the initial cycles (r = −0.62, p < 0.001), indicating that longer torsade de pointes had a faster rate than that at onset.

Conclusions. In patients with acquired prolonged repolarization, the spontaneous onset of ventricular arrhythmias was preceded by an increasing heart rate in the last minute and escalating oscillatory “short-long-short” cycle length patterns, with greater oscillations preceding torsade de pointes than salvos and isolated ventricular beats. These findings suggest that adrenergic- and pause-dependent mechanisms (possibly inducing afterdepolarizations and triggered activity) may have a synergetic role in the genesis of complex ventricular arrhythmias associated with delayed ventricular repolarization.     

Long QT syndrome and torsade de pointes in transient left ventricular apical ballooning syndrome

A recently reported cardiac syndrome of reversible left ventricular apical ballooning, also called Takotsubo cardiomyopathy or ampulla cardiomyopathy, clinically resembles acute myocardial infarction and presents with chest pain, anterior electrocardiographic changes and minimal elevation of cardiac enzymes in absence of myocardial ischemia or injury. Left ventricular function recovers completely in days to weeks. This syndrome is likely a non-ischemic, metabolic-dependent syndrome caused by stress-induced activation of the cardiac adrenoceptors, and results in markedly abnormal ventricular repolarization. Reported here is a case of left ventricular apical ballooning syndrome with QT interval prolongation in a young man who developed torsade de pointes and experienced aborted sudden cardiac death. Patient had a complete recovery of cardiac function and normalization of QT interval in a few days. The syndrome of transient left ventricular apical ballooning could be considered among the causes of long QT syndrome and torsade de pointes.     

Clinical observation on pause-dependent long QT syndrome and torsade de pointes ventricular tachycardia]

Ten patients with long QT syndromes (LQTs) and torsade de pointes (Tdp) were evaluated. The following features were noticed: (1) Serum potassium concentration was reduced in 5 of 10 patients (50.0%, mean value 3.0 mmol/L); (2) The QT interval (mean value 0.50s) was significantly prolonged in all patients; (3) A flat and wide T wave, an abnormal increase in U wave amplitude close to the end or the peak of the T wave and these changes were accentuated by pause or a sudden deceleration in ventricular rhythm; (4) The critical beat of Tdp inevitably started after the peak of the T wave of a markedly prolonged QT interval. Cycle lengths preceding torsade de pointes were shown in a pattern of short cycle-long QT-"late premature ventricular contraction" initiating sequence changes.     

Q-T prolongation and polymorphous (“torsade de pointes”) ventricular arrhythmias associated with organophosphorus insecticide poisoning

It is not generally appreciated in the Western world that organophosphorus poisoning may be associated with a serious and often fatal cardiac complication: Q-T interval prolongation with malignant ventricular arrhythmias of the “torsade de pointes” type. This Insidious complication may lead to delayed, sudden death after the patient appears to be well on the way to recovery from the other, more dramatic respiratory and neurologic symptoms. In this study 15 patients with organophosphorus poisoning are described. Q-T prolongation was observed in 14 and malignant tachyarrhythmlas in 6. In view of the dismal prognosis of these patients, ventricular pacing, previously used with success In other conditions associated with this syndrome, was tried in four patients and successfully shortened the Q-T interval and eliminated the arrhythmias. Isoproterenol did the same in a fifth patient. Awareness of this lethal, but preventable complication of organophosphorus poisoning is called for. Careful electrocardiographic monitoring is necessary until the Q-T interval returns to normal. Electrical pacing appears to be the treatment of choice for the tachyarrhythmias.     

Anorexia nervosa and sudden death

Necropsy findings and electrocardiograms from three women with anorexia nervosa were reviewed. Necropsy examination failed to establish an anatomic cause of death. Electrocardiograms recorded days or less before death showed various degrees of Q-T interval prolongation: Q-T intervals corrected for heart rate measured 0.61 s, 0.47 s, and 0.46 s, respectively. Terminal ventricular tachyarrhythmias were documented in two patients, including torsade de pointes in one. The necropsy and clinical findings in these three cases provide evidence that sudden death in anorexia nervosa, like sudden death in liquid-protein dieting, may result from ventricular tachyarrhythmias related to Q-T interval prolongation. For such patients, electrocardiographic monitoring should be routine.     

Torsade de Pointes Complicating the Treatment of Bleeding Esophageal Varices: Association with Neuroleptics, Vasopressin, and Electrolyte Imbalance

Torsade de pointes is an unusual life-threatening ventricular arrhythmia that has been associated with vasopressin, neuroleptic drugs, and electrolyte imbalances, including hypokaleniia and hypomagnesemia. Over a 9-month period, we observed torsade de pointes in three patients with cirrhosis and bleeding esophageal varices who did not have prior cardiac disease. All had received endoscopic sclerotherapy and continuous infusions of vasopressin and nitroglycerin. For sedation, two patients received haloperidol and one droperidol. In addition, two patients had either hypokalemia or hypomagnesemia. In all three patients, there was prolongation of the electrocardiographic QT interval and a "long-short" initiating sequence followed by ventricular tachycardia with torsade de pointes morphology. All were successfully cardioverted; there was one late death due to aspiration and septicemia. We conclude that cirrhotics with variceal hemorrhage may be at increased risk of developing this arrhythmia in the setting of treatment with vasopressin, sedation with neuroleptic drugs, and electrolyte abnormalities. We urge close monitoring of these patients for cardiac arrhythmia and recommend that neuroleptics be used cautiously, if at all.     

Incidence and clinical features of the quinidine-associated long QT syndrome: implications for patient care

Quinidine therapy is one of the most common causes of the acquired long QT syndrome and torsade de pointes. In reviewing clinical data in 24 patients with the quinidine-associated long QT syndrome, 20 of whom had torsade de pointes, we have delineated several heretofore unreported or underemphasized features. (1) This adverse drug reaction occurred either in patients who were being treated for frequent nonsustained ventricular arrhythmias or for atrial fibrillation or flutter. (2) In patients being treated for atrial fibrillation, torsade de pointes occurred only after conversion to sinus rhythm. (3) Although most patients developed the syndrome within days of starting quinidine, four had torsade de pointes during long-term quinidine therapy, usually in association with hypokalemia. (4) Because of the large experience with this entity at our institution, we have been able to estimate the risk as at least 1.5% per year. (5) Twenty of the 24 patients had at least one major, easily identifiable, associated risk factor including serum potassium below 3.5 mEq/L (four); serum potassium between 3.5 and 3.9 mEq/L (nine); high-grade atrioventricular block (four); and marked underlying, (unrecognized) QT prolongation (two). Plasma quinidine concentrations were low, being at or below the lower limit of the therapeutic range in half of patients. The ECG features typically included absence of marked QRS widening, marked QT prolongation (by definition), and a stereotypic series of cycle length changes just prior to the onset of torsade de pointes. Torsade de pointes started after the T wave of a markedly prolonged QT interval that followed a cycle that had been markedly prolonged (usually by a post ectopic pause).(ABSTRACT TRUNCATED AT 250 WORDS)     

Torsade de pointes complicating drug treatment of low-malignant forms of arrhythmia: Four case reports

In patients with malignant ventricular arrhythmias, antiarrhythmic therapy is known to carry a substantial risk of proarrhythmia. This risk is usually considered to be low when supraventricular arrhythmias or benign ventricular arrhythmias are considered. We were able to collect data on four patients without a history of life-threatening arrhythmias, in whom antiarrhythmic therapy was used and resulted in documented ventricular fibrillation or torsade de pointes. In Cases No. 1 and 2, atrial fibrillation was treated with either quinidine or quinidine and sotalol in combination. In both patients Holter monitoring, 4-12 h after conversion to sinus rhythm, documented the spontaneous occurrence of torsade de pointes degenerating into ventricular fibrillation and requiring DC shock for termination. In Case No. 3, atrial fibrillation was treated with sotalol and amiodarone for 2 months when incessant episodes of torsade de pointes were documented. In Case No. 4, frequent but unsustained ventricular arrhythmias were treated with amiodarone in a patient suffering dilative cardiomyopathy. After 6 days of treatment at a heart rate of 54 beats/min, a marked QT increase was associated with the occurrence of repetitive episodes of polymorphic ventricular tachycardia degenerating into ventricular fibrillation. None of the patients presented significant electrolyte abnormalities in the laboratory. A pathologic increase of the QTc-time was documented in Cases No. 1, 3, and 4. In all patients antiarrhythmic therapy was withdrawn after the proarrhythmic event and the patient became free of malignant tachyarrhythmias. Antiarrhythmic therapy also carries a considerable risk of proarrhythmia when “benign” cardiac arrhythmias are treated. The risk seems to be lower than in patients with malignant arrhythmias, however it includes the occurrence of lethal tachyarrhythmias. Special attention should be paid to the selection of antiarrhythmic agents when used in combination.     

Sudden death during ambulatory monitoring. Analysis of six cases

The ambulatory electrocardiographic recordings of six patients with coronary artery disease who died during monitoring were analyzed. In four patients, sinus rhythm was interrupted by sinoatrial, atrioventricular, nodal, or infra-His conduction abnormalities leading to bradyarrhythmic sudden death. Two patients died of sustained ventricular tachycardia or ventricular fibrillation. These data emphasize that the arrhythmias involved in the sudden death syndrome may be more heterogenous than currently appreciated.     

Electrocardiographic exercise testing and ambulatory monitoring to identify patients with ischemic heart disease at high risk of sudden death

Prognostic significance of ambulatory electrocardiographic monitoring and exercise testing was studied in 144 patients with established ischemic heart disease. A follow-up study showed that 10 sudden deaths occurred within 2 years. The univariates most strongly associated with the subsequent occurrence of sudden death included reduced maximal exercise heart rate, exercise-induced frequent ventricular arrhythmias, complex ventricular arrhythmias revealed by 24 hour ambulatory electrocardiographic monitoring and onset of S-T segment depression during exercise testing. Groups of patients at very high and very low risk of sudden death were identified using conjunction and inclusive disjunction of the foregoing variables. The presence of bivariate and trivariate combinations was associated with an increase up to 20-fold in the incidence of sudden death. Patients with the poorest prognosis were those who stopped exercise before achieving a high heart rate and who exhibited either pronounced electrocardiographic abnormalities during stress testing or complex ventricular arrhythmias during ambulatory monitoring. Combinations of exercise variables identified patients at a very high risk of sudden death, whereas combinations of monitoring variables appeared to be preferable for defining groups of patients at very low risk. The results obtained suggest that the two methods carry different prognostic information and, therefore, may complement each other in identifying potential victims of sudden cardiac death.     

QT interval prolongation, torsade de pointes and renal disease

Torsade de pointes is a form of polymorphic ventricular tachycardia occurring in a setting of prolonged QT interval on surface electrocardiogram. Several non-antiarrhythmic drugs including antibiotic and antipsychotic agents have been shown to prolong cardiac repolarization predisposing to torsade de pointes ventricular tachycardia. Blockade of the delayed rectifier (repolarising) potassium current and drug interactions with inhibitors of the cytochromes P450 (CYP)-mediated metabolism are the most common underlying mechanisms. Many antiarrhythmic drugs have been also implicated in prolonging QT interval and triggering torsades de pointes, especially during chronic therapy or in case of acute high dose toxicity. Progressive renal disease is associated from the earliest stages with increased QT interval and dispersal and with an increased risk of cardiovascular death, specifically sudden death. It has also been reported that cCorrected QT (QTc) interval prolongation and torsade de pointes are associated with end-stage renal disease (ESRD) and that they can be a cause of sudden death in ESRD. We present a case of torsade de pointes in a 82-year-old Italian woman with chronic renal failure.     

Gender differences in arrhythmias

Electrocardiographic and electrophysiologic differences between men and women have long been noted. Women have a higher intrinsic heart rate than men, along with a longer corrected QT interval and a shorter sinus nodal recovery time. The incidence of and risk factors for a variety of arrhythmias differ between men and women. Atrioventricular nodal reentry tachycardia has a 2:1 female-to-male predominance, while accessory pathways are twice as frequent in men. Although atrial fibrillation is more prevalent in men of all age groups, the absolute numbers of men and women with atrial fibrillation are equal, and the associated morbidity and mortality experienced by women with atrial fibrillation appear to be worse. Women have a lower incidence of sudden cardiac death, and female survivors of sudden cardiac death have a lower frequency of spontaneous or inducible ventricular tachycardia. On the other hand, drug-induced torsade de pointes and symptomatic long QT syndrome have a female predominance. Therefore, greater caution should be used when prescribing QT-prolonging drugs in women. The incidence of arrhythmias is increased during pregnancy, and management of pregnant patients poses a significant challenge. The mechanisms of these gender differences are unclear but may be related to hormonal effects and the shorter QT interval in adult males. Pharmacologic and nonpharmacologic therapies are usually equally efficacious, but the risks of pharmacologic therapy are different in men and women. Atrial fibrillation may be more difficult to treat in women.     

Correlates of cardiac and sudden death after ambulatory monitoring in a community hospital. Importance of clinical characteristics, congestive heart failure and tachyarrhythmias

To analyze the prognostic importance of arrhythmias on routine 24-hour ambulatory monitoring, we prospectively followed 755 consecutive patients undergoing monitoring at a community hospital in the context of usual medical care. Of the 755 patients, 114 (15%) had ventricular tachycardia on monitoring. At a mean follow-up of 38 months, multivariate survival analysis indicated that congestive heart failure was the strongest correlate of death from all causes (relative risk (RR) = 2.6), cardiac death (RR = 3.5), and the sudden cardiac death (RR = 5.6); ventricular tachycardia was significantly correlated with death from all causes and with cardiac death, but had only a borderline association with sudden cardiac death (RR = 1.9, p = 0.08). While ventricular tachycardia on ambulatory monitoring is of prognostic importance, congestive heart failure, as determined by routine clinical examination, was a more powerful prognostic correlate of deaths from all causes, death from cardiac causes, and sudden cardiac death.     

早期复极综合征并反复晕厥两家系报告

目的 探讨两个早期复极综合征(early repolarization syndrome,ERS)合并反复晕厥家系的临床特点及可能机制.方法 分别对两个先证者所在家系的所有家族成员进行常规临床检查和心电图、超声心动图、动态心电图、X线胸片、直立倾斜试验、生化等检查.结果 两家系中所有成员均无器质性心脏病的临床证据.先证者1反复心原性晕厥,静息心电图表现为ERS,反复发作尖端扭转型室性心动过速及心室颤动;其弟弟、儿子及侄儿均诊断为ERS,其他家族成员均未有心脏事件(晕厥、心脏骤停和心脏性猝死).先证者2表现为反复不明原因晕厥,心电图示ERS,其中V1～V3导联ST段弓背向上抬高;其父于65岁时心脏性猝死,其一侄儿诊断为ERS,余家族成员均正常.结论 ERS可表现为反复晕厥、尖端扭转型室性心动过速和心室颤动,不一定总是良性的临床过程.ERS与Brugada综合征可以共存于同一患者,但尚不能充分证明两者有共同的发生机制.遗传性家系的研究为进一步基因研究打下了坚实的基础.     

Diastolic micropotentials in high-resolution surface ECG in QT syndrome

Patients suffering from long QT syndrome are threatened by torsade de pointes tachycardias and sudden arrhythmic cardiac death. An inhomogenic sympathetic innervation of the heart with dominance of the left cervicothoracic sympathetic nerves has been considered to be a major cause of life threatening cardiac arrhythmias. This study presents the electrocardiographic and electrophysiologic results of 7 patients with long QT syndrome. In agreement with data published earlier our results of Holter monitoring, exercise testing and programmed electrical right ventricular stimulation were of no diagnostic or prognostic significance in predicting syncopal attacks or sudden arrhythmic cardiac death. Thus, the high resolution ECG methods played an important role in this study. During noninvasive recordings of signal averaged ECGs and high resolution surface ECGs with beat to beat registration, diastolic microvolt potentials could be detected in 6/7 patients within the ST segment and in 5/7 patients after the T wave. Our results evidently show that the signal averaged ECG and the high resolution surface ECG could be of diagnostic significance in patients with long QT syndrome.     

Iatrogenic torsade de pointes induced by thioridazine]

Torsade de pointes is a form of polymorphous ventricular tachycardia in which the polarity of the QRS complex exhibits phasic alterations in both axis. Traditionally, torsade de pointes has been described in association with a congenital or acquired (including drug and metabolic) causes of QT prolongation. Clinical outcomes range from asymptomatic, self-terminating arrhythmias to ventricular fibrillation resulting in cardiac arrest. For the treatment of torsade de pointes, the conventional antiarrhythmic drugs cannot be relied on, cardiac pacing should be instituted as soon as possible; however, as this technique may not always be immediately available, isoproterenol infusion may be the first-choice treatment. Potassium and magnesium repletion appear to be essential in abolishing drug-induced torsade de pointes. This report describes a case of thioridazine-induced torsade de pointes treated efficaciously with magnesium sulphate and overdrive right ventricular pacing.     

Torsade de pointes during administration of pentamidine isethionate

Pentamidine isethionate is a diamidine compound used in the treatment of a number of parasitic diseases, notably Pneumocystis carinii pneumonia. Although cases of sudden death have been reported during the administration of pentamidine, there have been no reported cases in the literature of pentamidine-associated arrhythmias. Reported in this study are two cases of torsade de pointes occurring during the prolonged administration of pentamidine. In addition, electrocardiographic changes of marked QT interval prolongation, pronounced precordial T wave abnormalities, and ST segment changes were shown in both patients. Mild hypomagnesemia coexisted in both cases, but torsade de pointes persisted in one patient and electrocardiographic changes remained in both cases despite magnesium replacement. QT interval prolongation and electrocardiographic abnormalities resolved slowly over several days to weeks, paralleling the known elimination kinetics of pentamidine. These data suggest a proarrhythmic effect of pentamidine isethionate.