Normalization of acquired QT prolongation in humans by intravenous potassium

BACKGROUND: QT interval prolongation and dispersion have been implicated in serious arrhythmias in congestive heart failure (CHF) and the congenital and drug-induced long-QT syndromes (LQTS). In a subset of the congenital LQTS, infusion of potassium can correct QT abnormalities, consistent with in vitro increases in outward currents such as I(Kr) or I(Kl) when extracellular potassium concentration ([K+]o) is increased. Furthermore, increasing [K+]o decreases the potency of I(Kr)-blocking drugs in vitro. The purpose of this study was to test the hypothesis that increasing [K+]o corrects QT abnormalities in CHF and in subjects treated with quinidine. METHODS AND RESULTS: KCl (maximum, 40 mEq) was infused into (1) 12 healthy subjects treated with quinidine sulfate (5 doses of 300 mg/5 h) or placebo and (2) 8 CHF patients and age-matched normal control subjects. Mean [K+] increased from 4 to 4.2 mEq/L to 4.7 to 5.2 mEq/L. Potassium infusion significantly reversed QTUc prolongation, especially in the precordial leads (quinidine, 590+/-79 to 479+/-35 [+/-SD] ms(1/2), P<.001; CHF, 521+/-110 to 431+/-47 ms(1/2), P<.05). There was no effect in either control group. Similarly, potassium decreased QTUc dispersion (quinidine, 210+/-62 to 130+/-75 ms(1/2), P<.01; CHF, 132+/-68 to 84+/-35 ms(1/2), P=.07) and was without effect in the control subjects. QT morphological abnormalities, including U waves and bifid T waves, were reversed by potassium. CONCLUSIONS: Potentially arrhythmogenic QT abnormalities during quinidine treatment and in CHF can be nearly normalized by modest elevation of serum potassium.     

QT prolongation and near fatal cardiac arrhythmia after intravenous tacrolimus administration: a case report

We have developed a technique of staining the anterior capsule with a solution of indocyanine green that facilitates performance of the circular continuous capsulorrhexis in eyes with a mature cataract. We compared the results of phacoemulsification and intraocular lens implantation in 10 eyes with the capsule stained with results of 10 eyes having the same procedure with standard circular continuous capsulorrhexis. The results of specular microscopy and laser flare-cell photometry showed no statistically significant differences between the 2 groups. Although the safety of intraocular indocyanine green dye has not yet been definitively established, the findings of this pilot study suggest that it is safe and useful in visualizing the anterior capsule of a mature cataract during cataract surgery.     

Measurement of the QT interval and the risk associated with QTc interval prolongation: a review

The accurate measurement of the QT interval and its correction or adjustment for cycle length, age, and gender have been topics of increasing interest over the course of the past 70 years. The availability of digitized electrocardiographic recordings on large normal populations together with statistical adjustment for pertinent covariates has provided useful data for defining QT interval prolongation. Data from the International Long QT Syndrome Registry indicate that the probabilistic risk of developing malignant arrhythmias in patients with QT prolongation is exponentially related to the length of the QTc interval. The risk is further accentuated by the development of T-wave alternans, particularly at very prolonged QTc intervals.     

The pre-clinical assessment of QT interval prolongation: a comparison of in vitro and in vivo methods

The literature was searched for in vivo dog studies reporting QT prolongation and in vitro studies reporting increased myocardial action potential duration, which indicates the potential to prolong QT interval, for nine non-cardiac drugs that have been reported to produce QT prolongation in man. The drugs were: astemizole; terfenadine; erythromycin; sparfloxacin; cisapride; probucol; terodiline; risperidone and sertindole. 1. There were reports of the appropriate finding with in vitro methods for six of the drugs and with in vivo methods for seven of the drugs. No reports were found concerning the remaining drugs with each method. This indicates that both methods are effective and each method would have correctly identified the drugs in question as having the potential to prolong the QT interval in man in all cases for which studies were reported. 2. This suggests that, if properly conducted, either method alone is sufficient for the pre-clinical assessment of QT interval prolongation. This does not support the routine use of both methods before the administration of new drugs to man.     

Case report: reversible QT prolongation with torsades de pointes in a patient with pimozide intoxication

Pimozide is a diphenylpiperidine neuroleptic with well characterized cardiovascular side effects including QT prolongation. So far, life-threatening cardiac arrhythmias, in particular torsades de pointes, have not been described in patients treated with pimozide. The authors describe a patient in whom torsades de pointes developed after the ingestion of 800 mg pimozide as a suicide attempt. After intravenous treatment with lidocaine and magnesium, the patient recovered completely and the QT interval had normalized 5 days after the intoxication. Potential mechanisms leading to torsades de pointes in patients treated with pimozide are discussed.     

Electrophysiologic effects and arrhythmogenic potential of diphemanil methylsulfate on rabbit purkinje fibers. Correlations with clinical observations of QT prolongation in pediatrics

Serious undesirable cardiac side effects have been reported with treatment with diphemanil methylsulfate (Prantal) in premature babies or neonates. To understand the origin of this problem, the authors undertook an electrophysiological study of the effects of this product in vitro on rabbit Purkinje fibres. In three separate series (N = 5 to N = 8), the effects of increasing concentrations (0.1 microM-30 microM) of diphemanil methylsulfate, different frequencies of stimulation (0.2 Hz, 1 Hz, 2 Hz) and duration of exposition (60 min followed by 120 min washout) were observed on the properties of the action potential. The results show a clearcut antiarrhythmic Class III type action characterised by a concentration-dependent prolongation of the action potential duration with an inverse frequency dependency without significant changes of the other parameters. During stimulation at 0.2 Hz, early post-depolarizations and induced activity were observed in 3/8 of the fibres exposed to 10 microM and 8/8 fibres exposed to 30 microM. The effect did not attain a steady state after 60 min of exposition. It was not reversed by 120 min of washout of the preparation. These results were compatible with the reported cardiac arrhythmic effects of prolongation of the QT interval and torsades de pointe.     

Micturition syncope

The micturition syncope is a special manifestation of the so called "situational syncopes". These reflex syncopes share efferent mechanisms with the neurocardiogenic, or vasovagal syncope. A case of a patient is reported, who presented with micturition syncope. The patient's tendency for vasovagal syncope was documented by a positive tilt table test. The uniform premonitory symptoms preceding the two fainting attacks indicated the relation between the episodes. The authors review the literature of the micturition syncope, and discuss the potential pathomechanisms.     

Bradycardia-induced syncope

Vascular surgeons well versed in peritoneal dialysis applications understand the importance of this modality among the limited options afforded to patients in renal failure. Peritoneal and hemodialysis strategies are interdependent and should be considered in concert. Careful assessment often shows that patients with diminishing vascular access have been overlooked as viable peritoneal dialysis candidates. This chapter summarizes peritoneal dialysis in terms of its history, physiological principles, indications, contraindications, catheter placement, types of administration, and the identification and management of complications.     

Vasovagal syncope and unexplained syncope: Concepts, treatments, and future perspectives.

Syncope (transient loss of consciousness) can lead to significant psychosocial and physical impairment and have a profound impact on the quality of life of the sufferer. While infrequently attended to, a psychological perspective may have much to offer within a comprehensive treatment plan. The present article reviews 26 articles that evaluate conventional (education, medication, cardiac pacemakers) and to a greater extent, complementary treatments (orthostatic training, applied tension, psychologically oriented interventions) designed to reduce the frequency and negative consequences of vasovagal and unexplained syncope. Applied tension demonstrated the greatest efficacy in reducing the frequency of vasovagal syncope. However, this intervention applies only to patients who experience a prodrome prior to fainting. Currently, no clinically proven treatment exists for patients with unexplained syncope or with vasovagal syncope without a prodromal phase. Suggestions regarding appropriate cognitive and/or behavioural interventions are provided based on the characteristics of the patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acceleration-induced action potential prolongation and early afterdepolarizations

INTRODUCTION: Precipitation of torsades de pointes (TdP) has been shown to be associated with acceleration of heart rate in both experimental and clinical studies. To gain insight into the cellular mechanism(s) responsible for the initiation of acceleration-induced TdP, we studied the effect of acceleration of pacing rate in canine left ventricular epicardial, M region, endocardial, and Purkinje fiber preparations pretreated with E-4031, an IKr blocker known to induce the long QT syndrome and TdP. METHODS AND RESULTS: Standard microelectrode techniques were used. E-4031 (1 to 2 microM) induced early after depolarization (EAD) activity in 31 of 36 M cell, 0 of 10 epicardial, 0 of 10 endocardial, and 9 of 12 Purkinje fiber preparations at basic cycle lengths (BCLs) > or = 800 msec. In 30 of 36 M cells, sudden acceleration from a BCL range of 900 to 4,000 msec to a range of 500 to 1,500 msec induced transient EAD activity if none existed before or increased the amplitude of EADs if already present. Acceleration-induced augmentation of EAD activity was far less impressive and less readily demonstrable in Purkinje fibers (4/12). In M cells, appearance of EAD activity during acceleration usually was accompanied by an abbreviation of action potential duration (APD). Within discrete ranges of rates in the physiologic range, acceleration caused a transient prolongation of APD in 38% of M cells, whether or not a distinct EAD was generated. Acceleration produced still more dramatic APD prolongation and EADs in M cells after the BCL was returned to the original slow rate. Epicardium and endocardium APD showed little change immediately after acceleration. A decrease of BCL as small as 10% and, in some cases, a single premature beat could promote EAD activity and APD prolongation in some M cells. Ryanodine (1 microM, 10/10), flunarizine (10 microM, 3/6), and low Na (97 vs 129 mM, 5/5) abolished the acceleration-induced EAD activity and APD prolongation as well as the EAD activity observed at slow rates in M cells pretreated with E-4031. CONCLUSION: Our results suggest that acceleration from an initially slow rate or a single premature beat can induce or facilitate transient EAD activity and APD prolongation in canine ventricular M cell preparations pretreated with an IKr blocker via a mechanism linked to intracellular calcium loading. Our data provide evidence in support of an important contribution of electrogenic Na/Ca exchange current to this process. These acceleration-induced changes can result in the development of triggered activity as well as a marked dispersion of repolarization in ventricular myocardium and, thus, may contribute to the precipitation of TdP in patients with the congenital (HERG defect) and acquired (drug-induced) long QT syndrome.     

Recognizing syncope: pitfalls and surprises

Loss of consciousness and falling are the key features of syncope. Common accompaniments include tonic and myoclonic muscle activity, eye deviations, automatisms, vocalizations and hallucinations which may render the distinction from epileptic seizures difficult. Differential diagnosis is based on the specific features and not the mere presence of these phenomena. Recognition of syncope depends also on accurate information about precipitants, premonitory symptoms and postictal events: the absence of postictal confusion has been identified as the single most powerful factor discriminating syncope from epileptic seizures whereas incontinence and head injury are common in both conditions. Investigations such as electroencephalogram, tilt testing and postictal prolactin or creatine kinase levels may be helpful but are never diagnostic in isolation. Exceptionally, hypoxic and epileptic mechanisms interact within a single attack.     

Association of an epsilon wave and syncope

BACKGROUND: Epsilon waves, rarely observed in clinical practice, result from late potentials favoring the development of ventricular rhythm disorders by reentry. CASE REPORT: A 53-year-old man with sequellar myocardial infarction experienced a syncope. The surface ECG recorded an epsilon wave. Programmed ventricular stimulation before and after anti-arrhythmia drugs triggered ventricular tachycardia which was hemodynamically poorly tolerated. A defibrillator was implanted and confirmed retrospectively the rhythmic origin of the syncope. DISCUSSION: The association of an epsilon wave and syncope should guide the etiology search towards severe ventricular rhythm disorders such as ventricular tachycardia. An electophysiologic study is required in order to determine the appropriate therapy and thus help avoid possibly fatal recurrence.