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Increased proinflammatory interleukin-6 (IL-6) levels are associated with acquired long QT-syndrome (LQTS) in patients with systemic inflammation, leading to higher risks for life-threatening polymorphic ventricular tachycardia such as Torsades de Pointes. However, the functional and molecular mechanisms of this association are not known. In most cases of acquired LQTS, the target ion channel is the human ether-á-go-go-related gene (hERG) encoding the rapid component of the delayed rectifier K current, IKr, which plays a critical role in cardiac repolarization. Here, we tested the hypothesis that IL-6 may cause QT prolongation by suppressing IKr. Electrophysiological and biochemical assays were used to assess the impact of IL-6 on the functional expression of IKr in HEK293 cells and adult guinea-pig ventricular myocytes (AGPVM). In HEK293 cells, IL-6 alone or in combination with the soluble IL-6 receptor (IL-6R), produced a significant depression of IKr peak and tail current densities. Block of IL-6R or Janus kinase (JAK) reversed the inhibitory effects of IL-6 on IKr. In AGPVM, IL-6 prolonged action potential duration (APD) which was further prolonged in the presence of IL-6R. Similar to heterologous cells, IL-6 reduced endogenous guinea pig ERG channel mRNA and protein expression. The data are first to demonstrate that IL-6 inhibition of IKr and the resulting prolongation of APD is mediated via IL-6R and JAK pathway activation and forms the basis for the observed clinical QT interval prolongation. These novel findings may guide the development of targeted anti-arrhythmic therapeutic interventions in patients with LQTS and inflammatory disorders. [ABSTRACT FROM AUTHOR]

Aims: To compare patients with atrial flutter (AFl) and 1:1 atrioventricular conduction (AVC) with patients with AFl and higher AVC. Methods: The characteristics of 19 patients with AFl and 1:1 AVC (group A) were compared with those of 116 consecutive patients with AFl and 2:1 AVC or higher degree AV block (group B). Results: Age, gender, and left ventricular function were similar in the two groups. In group A versus group B, more patients had no structural heart disease (42% vs 17%, P < 0.05) and syncope/presyncope (90% vs 12%, P < 0.05). The AFl cycle length (CL) in group A was longer than in group B (265 ± 24 ms vs 241 ± 26 ms, P < 0.01). The transition from AFl with 1:1 to 2:1 AVC or vice versa was associated with small but definite changes in AFl CL, which showed larger variations in response to sympathetic stimulation. In group A patients who were studied off drugs, the atrial-His interval was not different from group B, but maximal atrial pacing rate with 1:1 AVC was faster. In group A, five patients were misdiagnosed as ventricular tachyarrhythmias, and three with a defibrillator received inappropriate shocks. Four patients had ablation of AVC and six had ablation of AFl circuit. Conclusions: The main difference between groups A and B may be an inherent capacity of the AV node for faster conduction, especially in response to increased sympathetic tone. The latter affects not only AVC but also the AFl CL. One should be aware of the different presentations of AFl with 1:1 AVC to avoid misdiagnosis/mismanagement and to consider the diagnosis in patients with narrow or wide QRS tachycardia and rates above 220/min. [ABSTRACT FROM AUTHOR]

Introduction: Atrial standstill is a rare heterogeneous arrhythmia characterized by electrical and mechanical standstill and electrical inexcitability. A long-lasting progressive form is seen with cardiac and neuromuscular diseases, and a familial or idiopathic form may have a genetic basis. A transient form was described secondary to drug intoxication, electrolyte imbalance, cardiac inflammation, and ischemia. Methods: We investigated three patients with long-standing atrial tachyarrhythmia (AT) (atrial flutter in two, and focal atrial tachycardia in one). All patients underwent a complete electrophysiological study with mapping of right and left atrial activity and radiofrequency ablation (RF Abl) of AT. Results: Following RF Abl of AT, all three patients manifested transient atrial electrical silence in the absence of known reversible causes. Atrial electrical silence was observed when, following AT termination, an escape atrioventricular (AV) junctional rhythm (in two patients) and an escape VVI pacemaker rhythm (in one patient) showed transient ventriculo-atrial (VA) conduction block (up to 30 seconds). A dominant sinus rhythm was observed to return 30 minutes, 90 minutes, and 12 hours, respectively, in the three patients. Two patients received a dual chamber pacemaker and a decision was made not to upgrade the patient with VVI pacemaker. Discussion and Conclusions: The present report expands the spectrum of the syndrome of atrial standstill and raises interesting questions regarding possible electrophysiologic mechanism(s) of prolonged post overdrive atrial standstill. The report suggests that chronic overdrive of sinus and subsidiary atrial pacemakers may result in calcium overloading of cardiac cells, which is known to cause suppression of pacemaker activity as well as increased intracellular resistance. These mechanisms can possibly result in either prolonged suppression of sinus and atrial pacemaker activity and/or pacemaker exit block. [ABSTRACT FROM AUTHOR]

Describes the case of a 76-year-old man diagnosed with drug-induced Torsades de Pointes. Presenting signs and symptoms including acute asthmatic episode and premature ventricular contractions; Past medical history; Diagnostic procedures; Results of laboratory tests; Treatment with the insertion of two bipolar catheters; Outcome.

The effects of a single intravenous infusion of 750 mg of procainamide was studied in 12 patients with symptomatic chronic recurrent venlricular tachycardia in whom arrhythmias could reproducibly be initiated and terminated by programmed electrical stimulation of the heart. Sustained ventricular tachycardia was induced in 6 patients and non-sustained tachycardia was induced in the remaining 6 patients during control studies. Following procainamide (plasma level 10.3 ± 3.7 mcg/ml], ventricular tachycardia could be induced in 10/12 patients, sustained in 4 patients and non-sustained in the remaining 6 patients. In 8/12 patients (66%). induction of ventricular tachycardia was facilitated as demonstrated by: (1) tachycardia zone was widened in 4 patients and was unchanged in another 3 patients; (2) non-sustained ventricular tachycardia was changed to sustained ventricular tachycardia in one patient. The ventricular tachycardia had a faster rate and a different QRS morphology; [3] in 4 patients tachycardia was inducible with a lesser number of extrastimuli and/ or by spontaneously occurring ventricular premature depolarization and; (4) increase of the number of induced ventricular responses of non-sustained ventricular tachycardia. In 4/12 patients )(33%), procainamide abolished or modified the induction of ventricular tachycardia as demonstrated by: (1) inability to induce ventricular tachycardia in 2 patients; (2) narrowing of the tachycardia zone and conversion from sustained into non-sustained ventricular tachycardia (one patient) and; (3) decrease in the number of induced ventricular responses in one patient. The response to procainamide could not be predicted from rates of spontaneous ventricular tachycardia, induced ventricular tachycardia during control studies, degree of slowing of ventricular tachycardia or from prolongation of the coupling interval after procainamide. These results suggest that instead of abolishing the arrhythmia, procainamide in frequently employed doses in patients with chronic recurrent ventricular tachycardia can facilitate its initiation sometimes at even faster rates. Patients not responsive to the usual doses of procainamide should undergo acute drug testing trials to determine the optimal dose/drug levels. [ABSTRACT FROM AUTHOR]

The value of signal-averaged P-wave electrocardiogram and echocardiography for predicting recurrent atrial tachyarrhythmias was prospectively investigated in 60 patients presenting with paroxysmal atrial fibrillation or flutter. All patients were followed up for 1 year after restoration of sinus rhythm. A stepwise discriminant function analysis sac used to identify variables predicting recurrent atrial tachyarrhythmias. Analyzed variables included signal-averaged P-wave duration in 3 bipolar orthogonal leads (X,Y,Z) and their vector magnitude as well as left and right atrial dimensions and volumes. During follow-up, 25 patients had recurrent curial tachyarrhythmias, while 35 did not. Using discriminant function analysis, the left atrial antero-superior dimension was found to be the only variable predicting the recurrence of atrial tachyarrhythmias (P< 0.0038) and was able to correctly classify 65% of the study patients. It was concluded that, in patients with paroxysmal atrial fibrillation or flutter, the traditionally used determination of left atrial dimension was the variable most closely associated with a high risk for recurrent tacharrhythmias. The signal-averaged P-wave duration did plot improve tachyarrhythmia prediction. [ABSTRACT FROM AUTHOR]

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 heat 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 u 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. [ABSTRACT FROM AUTHOR]

Asynchronous pacing during the presence of electromagnetic interference or other sources of "noise" is a protective mechanism available to prevent pacemaker output inhibition. We describe a patient with a DDD pacemaker who had asynchronous dual chamber or noise reversion pacing as a consequence of repetitive signals (QRS complexes) falling into the noise sampling period (NSP) of the pacemaker ventricular refractory period. During supraventricular tachycardi at a rate of 215 bpm, noise reversion mode pacing occurred when QRS complexes were well detected immediately after the termination of a normal pacemaker ventricular refractory period and treated as a premature ventricular depolarization, resulting in automatic refractory period extension. Recycling of this extended refractory period occurred when consecutive QRS complexes were detected during the NSP and forced asynchronous dual chamber pacing at the programmed lower rate. The mechanism is presented and was supported by subthreshold esophageal pacing simulating the tachycadia and initiating the noise reversion response. [ABSTRACT FROM AUTHOR]

Presents summaries of pertinent data on attempted ablation of the atrioventricular juntion and ventricular tachycardia foci. Catheter ablation of the atrioventricular junction; Analysis of catheter ablation of ventricular tachycardia foci.

The mechanisms of resetting, entrainment. acceleration, or termination of reentrant ventricular tachycardia by programmed electrical stimulation were studied in the canine post-infarction model. In this model, reentrant circuits were localized in the epicardial layer overlying the infarction and were accessible to detailed mapping by multiplexer techniques. The reentrant circuit has a characteristic figure-eight configuration in the form of two circulating wavefronts around arcs of functional conduction block that coalesce into a slow common reentrant wavefront. Termination of reentrant tachy-cardia occurred when a stimulated wavefront arrived earlier to a strategically located area in the proximal portion of the zone of slow conduction, before refractoriness expired distally, resulting in conduction block. The three factors that determined if the stimulated wavefront could reach this zone in time for conduction block were: (1) the cycle length of stimulation; (2) the number of stimulated beats, and (3) the site of stimulation. The most optimal situation for stimulated termination of reentry was a critically coupled single stimulus applied to the ischemic zone close to the proximal side of the zone of slow conduction that captured locally and conducted prematurely to the strategic zone for conduction block. When a single stimulated wavefront failed to terminate reentry, one or more subsequent wavefronts succeeded. However, the stimulated train had to be terminated following the beat that interrupted reentry. Otherwise, a subsequent stimulated beat could reinitiate the same reentrant circuit or induce a different circuit. The new circuit could have a shorter revolution time, resulting in tachycardia acceleration , and occasionally degeneration into ventricular fibrillation. Overdrive termination of reentry required both a critical cycle length of stimulation and a critical number of beats in a stimulated train. Otherwise, the stimulated train could establish a new.. [ABSTRACT FROM AUTHOR]

Catheter ablation of ventricular tachycardia is a procedure of last resort in critically III patients. The Percutaneous Cardiac Mapping and Ablation Registry was able to collect data on 88 patients undergoing ablation of ventricular tachycardia foci. The mean following interval for the group was 10 ± 8 months. Results were divided into three categories: Group I patients remained asymptomatic and were on no antiarrhythmic medications (33%); Group 11 remained asymptomatic and took antiarrhythmic agents (38%); Group III patients were considered unsuccessful and consisted of 29 percent of the total. More than one-third of patients received two shocks; the remainder received from one to five shocks. Overall mortality included four procedure-related deaths and total follow- up mortality was 25 percent. Catheter ablation for ventricular tachycardia should be undertaken only in highly specialized centers with an expert and experienced electrophysiologist with immediate surgical back-up available. [ABSTRACT FROM AUTHOR]

Details the evidence that early afterdepolarizations (EAD) and early afterdepolarization-induced triggered activity play a significant role in the clinical syndrome of long QTU heart wave and polymorphic ventricular tachyarrhythmias. Definition of EAD; Steps required for the manifestation of early afterdepolarization-induced triggered activity; Ionic mechanisms of repolarization;

Presents a case report of an elderly female patient who was referred for cardiac resynchronization therapy (CRT) due to refractory heart failure. Medical history; Effect of CRT on ventricular function; Discussion on transmural dispersion and intraventricular conduction disorder; Impact of CRT on the frequency of ventricular tachyarrhythmias.

Comments on a study regarding the electrophysiologic mechanism of polypleomorphic ventricular tachycardia (PVT). Definition of Torsades de pointes (TdP); Significance of the electrophysiologic mechanism for PVT to the proper management of individual patients; Emphasis on the difference of mechanism for transition of the QRS configuration of TdP in long QT syndrome.