bluuebunny/crossref_metadata_2025 huggingface dataset:
Discrimination of Sinus Rhythm, Atrial Flutter, and Atrial Fibrillation Using Bipolar Endocardial Signals
Authors: JUNG JENS , HOHENBERG GREGOR , HEISEL ARMIN , STRAUSS DANIEL , SCHIEFFER HERMANN , ERIES ROLAND
Published: April 2007

Discrimination of NSR, AFL, and AF. Introduction: Analysis of endocardial signals obtained from an electrode located in the right atrium as realized in newly designed dual chamber, implantable cardioverter defibrillators might be used to provide additional therapeutic options, such as overdrive pacing or low‐energy atrial cardioversion for the treatment of concomitant atrial flutter (AFL) or atrial fibrillation (AF). Therefore, we developed a computer algorithm for discrimination of normal sinus rhythm (NSR), AFL, and AF that may lead to adequate differential therapy of atrial tachyarrhythmias in an automated mode.

Methods and Results: During an electrophysiologic study, bipolar endocardial signals from the high right atrium were obtained in 28 patients during sustained AFL or AF and after restoration of NSR. A total of 286 data segments of 5‐second duration were recorded (NSR: 96, AFL: 86, AF: 104). Mean atrial cycle length (MCL), standard deviation of mean atrial cycle length (SDCK), and index of irregularity (IR). defined as the ratio between MCL and SDCL, were calculated for each data segment. A cutoff of 315 msec for MCL allowed discrimination of NSR from atrial tachyarrhythmias with 100% sensitivity and specificity. For discrimination of AF from AFI‐ by using SDCL, a cutoff value of 11.5 msec led to a sensitivity of 99% and a specificity of 90%. Best discrimination of AF from AFL was found for the criterion IR ≥ 7.5%, resulting in a sensitivity of 100% with a specificity of 95% for AF detection.

Conclusion: The investigated algorithm provides discrimination of NSR, AFL, and AF with high sensitivity and specificity. Incorporation of this algorithm in an implantable automated antitachycardia device may lead to adequate differential therapy in patients suffering from spontaneous episodes of AF and AFL.
Organized Activation During Atrial Fibrillation in Man
Authors: ROITHINGER FRANZ X. , Groenewegen ARNE Sippens , KARCH MARTIN R. , STEINER PAUL R. , ELLIS WILLARD S. , LESH MICHAEL D.
Published: April 2007

Atrial Fibrillation Organization. Introduction: Atrial fibrillation is not entirely random, but little is known about the spatiotemporal endocardial organization and its surface ECG manifestations.

Methods and Results: In 16 patients with atrial fibrillation (chronic, n = 14), endocardial mapping of the trabeculated, the posteroseptal smooth right atrium, and the coronary sinus was performed using multipolar catheters. The surface ECG was analyzed by determining “fibrillation wave” (F wave) amplitude, rate, and polarity. During 50 minutes of atrial fibrillation, an organized activation was present 72%± 32% of the analyzed time on the trabeculated, 19%± 15% on the smooth right atrium (P < 0.01), and 51%± 33% along the coronary sinus (P < 0.05). The direction of organized activation was craniocaudal in 72%± 16%. caudocranial in 10%± 9% (P < 0.01), and indeterminable in 18%± 11%. The mean surface F wave amplitude in lead V1 was 0.128 ± 0.06 mV during 28 seconds of atrial fibrillation with a craniocaudal direction of activation and 0.065 ± 0.02 mV during a disorganized activation (P < 0.01). A stable relation between surface F waves and organized trabeculated right atrial activation was observed, and the mean F wave cycle length (190 ± 27 msec) was highly comparable to the simultaneously measured endocardial cycle length (191 ± 27 msec, correlation coefficient 0.97). F wave polarity in V1 was positive in 12 of 14 patients during craniocaudal and negative in 11 of 14 patients during caudocranial rigbt atrial free‐wall activation.

Conclusion: An organized activation during atrial fibrillation with a predominant craniocaudal direction on the trabeculated right atrium is frequently present and influences the appearance of “coarse” or “fine” atrial fibrillation as well as F wave polarity on the surface ECG.
Hybrid Pharmacologic and Ablative Therapy: A Novel and Effective Approach for the Management of Atrial Fibrillation
Authors: HUANG DAVID T. , MONAHAN KEVIN M. , ZIMETBAUM PETER , PAPAGEORGIOU PANOGIOTIS , MEPSTEIN LAURENCE , JOSEPHSON MARK E.
Published: April 2007

Hybrid Therapy for Atrial Fibrillation. Introduction: Maintenance of sinus rhythm in patients with recurrent atrial fibrillation is often difficult to achieve with pharmacologic therapy. Complex catheter ablative procedures are being developed, but efficacy and safety issues remain to be clarified. We hypothesized that combined pharmacologic and simple ablative therapies in a targeted subset of patients will improve success in the treatment of atrial fibrillation.

Methods and Results: We identified 13 patients (mean age 61.5 ± 16.2 years) with atrial fibrillation who converted to electrocardiographic atrial flutter during antiarrhythmic drug treatment. Surface ECG suggested “typical” atrial flutter in 11 patients and “atypical” atrial flutter in 2. Intracardiac mapping and entrainment studies revealed 9 patients had counter‐clockwise isthmus‐dependent atrial flutter, and the remaining 4 had complex activation patterns, suggesting the presence of multiple wavefronts. All 9 patients with typical atrial flutter underwent successful ablation. None of the 4 patients with complex activation patterns had successful ablation. Patients were followed for recurrences of atrial arrhythmias via clinic visits, record review, and interviews. In patients who underwent successful ablation and continued on antiarrhythmic drugs, 88.9% remain in sinus rhythm after a mean follow‐up of 14.3 ± 6.9 months (range 1 to 28).

Conclusion: In patients who experience conversion of atrial fibrillation to atrial flutter during antiarrhythmic drug treatment, ablation and continuation of pharmacologic therapy is a safe and effective means of achieving and maintaining sinus rhythm.
Atrioventricular Nodal Reentry Tachycardia in Patients with Sinus Node Dysfunction: Electrophysiologic Characteristics, Clinical Presentation, and Results of Slow Pathway Ablation
Authors: KREINER GERHARD , FREY BERNHARD , GÖSSINGER HEINZ DAVID
Published: April 2007

AVNRT and Sinus Node Dysfunction. Introduction: Sinus node dysfunction (SND) is frequently associated with impaired AV conduction. This study investigated the electrophysiologic properties of dual AV nodal pathways in patients suffering from both SND and AV nodal reentrant tachycardia (AVNRT).

Methods and Results: Two groups of patients with slow‐fast AVNRT underwent invasive electrophysiologic testing and catheter ablation of the slow pathway. Group A comprised 10 patients with SND (age 70 ± 8 years), (Group B included 10 age‐matched patients without SND (age 69 ± 7 years; P = NS) who served as controls. Patients of group A exhibited prolongation of the anterograde Wenckebach cycle lengths (WBCLs) of both the fast pathway (559 ± 96 vs 361 ± 38 msec; P < 0.01) and the slow pathway (409 ± 57 vs 339 ± 32 ms; P < 0.01). However, the delta between the WBCLs of the fast and the slow pathways was larger in patients of group A (150 ± 80 vs 22 ± 20 msec; P < 0.01). Retrograde fast pathway conduction was well preserved with no difference in WBCLs (356 ± 42 vs 330 ± 47 msec; P = NS). Cycle lengths of AVNRT were longer in group A (468 ± 46 vs 363 ± 37 msec; P < 0.01). Clinically, all patients of group A suffered from multiple episodes of AVNRT per week, which was not the case in any patient of group B (P < 0.01). Catheter ablation of the slow pathway eliminated AVNRT in all patients without complications.

Conclusions: Patients with AVNRT and SND exhibit characteristic electrophysiologic alterations of both AV nodal pathways. Clinically, this results in significantly more frequent episodes of tachycardia. Slow pathway ablation appears to be safe and effective in these patients.
Dual Morphology of Idiopathic Ventricular Tachycardia
Authors: LOKHANDWALA YASH Y. , VORA AMIT M. , NAIK AJAY M. , NABAR ASHISH , KAVTHALE SANTOSH
Published: April 2007

Dual Morphology of Idiopathic VT. Introduction: Idiopathic ventricular tachycardia (VT) typically has a single morphology originating either in the right ventricular outflow tract (RVOT)or near the posterior fascicle of the left ventricle (LV) in most instances. We present our observations in six patients with idiopathic VT in whom two morphologies were present.

Methods and Results: Of 55 patients with idiopathic VT who underwent radiofrequency (RF) ablation. 44 had LV “fascicular” tachycardia, whereas 11 had RVOT tachycardia. During RF energy delivery, there was a change in VT morphology in two patients with idiopathic LV tachycardia. This second morphology was not ablated initially, recurred at follow‐up, and was reablated successfully. In two additional patients with idiopathic LV tachycardia, a second VT was inducible after ablation of the “clinical” VT. This second morphology recurred at follow‐up and was ablated successfully in one patient. The site where the second VT was ablated in all the three patients was remote from that of the first VT. In two patients with RVOT tachycardia, a second VT, originating from a different area of the RVOT, was induced after RF ablation of the “clinical” VT. This second VT recurred at follow‐up and was reablated successfully in one patient.

Conclusion: Idiopathic VT is a more heterogenous entity than hitherto believed. A second VT was seen in 11% of patients during or after RF ablation of the “clinical” VT. The appearance of a second VT suggests either a different exit site of the same circuit or another site of origin.
Amiodarone Reduces the Prevalence of T Wave Alternans in a Population with Ventricular Tachyarrhythmias
Authors: GROH WILLIAM J , SHINN TIMOTHY S. , ENGELSTEIN ERICA E. , ZIPES DOUGLAS P.
Published: April 2007

Amiodarone and the Presence of TWA. Introduction: Testing for the presence of microvolt T wave alternans (TWA) is useful for arrhythmic risk stratification. Whether antiarrhythmic pharmacotherapy affects the presence of TWA is unknown. We tested whether patients with known ventricular tachyarrhythmias who were receiving amiodarone were less likely to manifest TWA as compared with those not receiving amiodarone.

Methods and Results: Forty‐four patients with a history of ventricular tachyarrhythmias and an implantable cardioverter defibrillator (ICD) implanted at least 1 month earlier underwent TWA testing. In this group, 14 patients were receiving amiodarone and 30 were not. Indeterminate test results occurred in 13 patients without a significant difference in those receiving or not receiving amiodarone. In the 31 patients with determinate TWA testing, a positive test was less likely in those receiving amiodarone (1 of 9 [11%]) as compared with those not receiving amiodarone (14 of 22 [64%]; P = 0.04). During a follow‐up period averaging 0.9 ± 0.2 years, the presence of TWA (P = 0.04) and decreased left ventricular ejection fraction (P = 0.05) predicted appropriate ICD therapy for ventricular tachyarrhythmias.

Conclusion: The prevalence of TWA was decreased in a chronic ventricular tachyarrhythmic population receiving amiodarone as compared with a population not receiving amiodarone.
Accuracy and Limitations of Published Algorithms Using the Twelve‐Lead Electrocardiogram to Localize Overt Atrioventricular Accessory Pathways
Authors: BASIOUNY TAREK , DE CHILLOU CHRISTIAN , FAREH SAMIR , KIRKORIAN GILBERT , MESSIER MARC , SADOUL NICOLAS , CHEVALIER PHILLIPE , MAGNIN‐POULL ISABELLE , BLANKOFF IVAN , CHEN JIAN , TOUBOUL PAUL , ALIOT ETIENNE
Published: April 2007

Accessory Pathway Localization. Introduction: The purpose of this study was to evaluate the accuracy and limitations of published algorithms using the 12‐lead ECG to localize AV accessary pathways (APs).

Methods and Results: The 11 relevant algorithms found in the literature (MEDLINE database and major scientific sessions) were tested on a series of 266 consecutive patients who successfully underwent radiofrequency catheter ablation of a single overt AV AP. The positive predictive values (PPV) of the algorithms in applicable patients were significantly lower for algorithms with > 6 accessory location sites (40.6%± 10.9% vs 61.2%± 8.0%; P < 0.03) and show a tendency for algorithms not relying on delta wave polarity but on QRS polarity only (36.6%± 11.2% vs 52.3%± 13.1%; P = 0.09). The PPV in applicable patients is related to the AP location (P < 0.001) and ranked from the highest to the lowest as follows: left lateral (mean PPV = 86.3%), posteroseptal (mean PPV = 65.2%), right anteroseptal (mean PPV = 45.2%), and right posterolateral (mean PPV = 23.4%).

Conclusion: Our study suggests that the accuracy of algorithms relying on the 12‐lead ECG depends on AP locations as defined in the algorithms and on the number of AP sites. The accuracy tends to be lower when delta wave polarity is not included in the algorithm's architecture. This should be considered when using these algorithms or when building new ones.
Cardiac Conduction Abnormalities in Mice Lacking the Gap Junction Protein Connexin40
Authors: VERHEULE SANDER , Van BATENBURG CHRISTEL A.J.A.C. , COENJAERTS FRANK E.J. , KIRCHHOFE SUSANNE , WILLECKE KLAUS , JONGSMA HABO J.
Published: April 2007

Cardiac Conduction in C×40−/− Mice. Introduction: The gap junction protein connexin40 (C×40) normally is expressed in the murine atrial myocardium and ventricular conduction system. In mice lacking C×40, several changes in the surface ECG have been described. In this study, we analyzed cardiac conduction in more detail.

Methods and Results: In open chest mice under urethane anesthesia, epicardial electrodes were used to determine a number of atrial and ventricular pacing parameters. The corrected sinus node recovery time was significantly longer in C×40−/− mice than in C×40+/+ mice (44.4 ± 7.2 msec vs 35.5 ± 8.0 msec). In addition, the Wenckebach period was longer in C×40−/− mice compared with the wild type (84.6 ± 5.4 msec vs 78.8 ± 3.6 msec), with the AV node probably limiting AV conduction in both cases. Whereas arrhythmias could not be induced by ventricular burst pacing in any of the mice, atrial burst pacing induced atrial tachyarrhythmias in 5 of 10 C×40−/− mice, but not in any of 9 Cx40−/− mice. Conduction velocities were measured in vivo using an array of unipolar recording electrodes. Ventricular conduction velocity did not differ between the groups, but atrial conduction velocity was reduced by 30% in C×40−/− mice compared with the wild type. Heterozygous C×40+/− mice did not differ significantly from the wild type in any respect.

Conclusion: These findings indicate that in the atria and the AV conduction system, C×40 is an important determinant of conduction.
Evidence of Three‐Dimensional Scroll Waves with Ribbon‐Shaped Filament as a Mechanism of Ventricular Tachycardia in the Isolated Rabbit Heart
Authors: EFIMOV IGOR R. , SIDOROV VENIAMIN , CHENG YUANNA , WOLLENZIER BRIAN
Published: April 2007

Scroll Waves in the Heart. Introduction: Rotating vortices have been observed in excitable media of different nature. Vortices may sustain life or kill in different species, by underlining morphogenesis in Dictiostelium discoideum during starvation, or arrhythmias during sudden cardiac death in mammals. Investigation of vortices in the heart has been limited by two‐dimensional experimental techniques. In contrast, three‐dimensional (3D) Belousov‐Zhabotinsky excitable medium and mathematical models have been shown to sustain scroll‐shaped waves. The heart is a 3D structure; therefore, scroll waves may underlie cardiac arrhythmias.

Methods and Results: We used potentiometric dye and optical mapping techniques to study vortices during ventricular arrhythmias. The core of all observed vortices were linearly shaped and ≥ 9 mm (48 episodes, six hearts). As shown by Allessie et al. in the rabbit atrium, ventricular signals recorded within 1 to 2 mm from the line of block were dual humped, suggesting there is electrotonic interaction across the line of block. We hypothesized that the line of block represents epicardial intersection of ribbon‐shaped filaments, which in some cases may be oriented under an angle or parallel to the epicardium. In 14 episodes we observed dualhumped optical recordings at one side of the line of block at a distance up to 12 mm. The two humps may represent the signatures of two activation wave fronts propagating above and below the filament, which in this area is close to the epicardial surface. The activation sequence of the two waves is consistent with the idea of a scroll wave with ribbon‐like filament.

Conclusion: Our data provide new insights into the shape and dynamics of the filament of the 3D scroll wave, which underlies the mechanism of ventricular tachycardia in the rabbit heart. The filament of the scroll wave may be ribbon shaped, with a significant width ≥ 9 mm and a thickness of 1 to 2 mm. No evidence of fully excitable cells in the core of vortex was observed.
High‐Resolution Mapping and Histologic Examination of Long Radiofrequency Lesions in Canine Atria
Authors: TAYLOR GREGG W. , WALCOTT GREGORY P. , HALL JEFFREY A. , BISHOP SANFORD , KAY G. NEAL , IDEKER RAYMOND E.
Published: April 2007

High‐Resolution Mapping and Histologic Examination. Introduction: Catheter ablation may prevent conduction of multiple atrial wavefronts and/or reduce the critical mass of atrial myocardium required to sustain fibrillation. The purpose of this study was to examine the effect of radiofrequency (RF) energy application on conduction in canine atria by performing high‐density epicardial mapping and careful histologic examination of the ablation zone.

Methods and Results: RF energy was applied to the right atrial endocardium in nine anesthetized mongrel dogs in an attempt to create a line of conduction block spanning; the vertical length of a 504‐cbannel epicardial mapping plaque. The mean length and width of the histologically determined ablation zone was 34 ± 4 and 7.3 ± 2.6 mm, respectively. No thrombus was present. Conduction block that spanned the mapping plaque in 6 of 9 animals was matched histologically by continuous transmural necrosis in five. In one, only a portion of the ablation zone was transmural; the remainder was wide but nontransmural. In 2 of 3 animals with conduction, a narrow region was present where continuous transmural necrosis was absent. In the other animal, conduction was present despite continuous transmural necrosis.

Conclusion: Conduction block usually occurred when continuous transmural necrosis was present, and conduction usually persisted when continuous transmural necrosis was absent. However, important exceptions were observed, including block when the ablation zone was wide but nontransmural, and conduction despite a thin line of continuous transmural necrosis.
Anatomy of the Left Atrium:
Authors: YEN HO SIEW , SANCHEZ‐QUINTANA DAMIAN , CABRERA JOSE ANGEL , ANDERSON ROBERT H.
Published: April 2007

Anatomy of the Left Atrium. Introduction: The feasibility of treating atrial fibrillation with radiofrequency ablation has revived interest in the structure of the left atrium, a chamber that has been neglected in many textbooks of anatomy.

Methods and Results: We reviewed the gross structure of the left atrium by examining the septum, the appendage, and insertions of the pulmonary veins in normal hearts. The limited extent of the true septal component is relevant to procedures using the transseptal approach. On gross examination, the musculature of the atrial wall is composed of overlapping bundles of aligned fibers that, in the majority of hearts, are arranged in characteristic patterns with only minor individual variations. Muscular sleeves extend into the walls of the pulmonary veins to varying distances. The longest sleeves are in the left upper veins. Bachmann's bundle anteriorly, and other smaller bundles superiorly and posteriorly, bridge the septal raphe to blend with musculature of the right atrium. Tongues of left atrial musculature from the posterior wall also extend into the wall of the coronary sinus.

Conclusion: The left atrium is more complex than usually conceived. Understanding its structure, and the arrangement of its musculature, will help in improving strategies for linear lesions when attempting to compartmentalize the chamber, or when placing focal lesions for ablating ectopic sources.
Sinusoidal Stimulation of Myocardial Tissue:
Authors: MEUNIER JASON M. , TRAYANOVA NATALIA A. , GRAY RICHARD A.
Published: April 2007

Sinusoidal Stimulation of Cardiac Cells. Introduction: Cardiac tissue subjected to sinasoidal stimulus Is characterized by action potentials (APs) that have extended plateau phases, sustained for the duration of the stimulus. Extended action potential durations (APDs) are beneficial because they disrupt wandering wavelets in the fibrillating heart. To investigate the mechanisms by which periodic stimulus affects cardiac tissue, particularly the development of sustained depolarization, computer simulations of single cardiac cells exposed to alternating current (AC) are performed.

Methods and Results: Two modes of stimulation of the cell are examined: external field stimulation and transmembrane current injection. Several membrane models, including Luo‐Rudy I and II, are used in the simulations. External AC field stimuli increase the APD of the single cell. The extended plateau of the cellular AP is characterized by periodic oscillations that are 1:2 phase locked with the applied stimulus. This specific behavior is due to the variations in stimulus magnitude and polarity along the cell border, which elicit opposite electrical responses from the cell sides. These pointwise responses are averaged in the macroscopic cellular response and result in sustained oscillatory depolarization that lasts for the duration of the stimulus. In contrast, the cell undergoing current injection does not develop an extended APD.

Conclusion: The simulations demonstrate that variation of membrane potential within a cell is of paramount importance to the formation of an extended AP plateau in response to AC stimulation.
Epicardial Mapping and Radiofrequency Catheter Ablation of Ischemic Ventricular Tachycardia Using a Three‐Dimensional Nonfluoroscopic Mapping System
Authors: TOMASSONI GERY , STANTON MIKE , RICHEY MARK , LEONELLI FABIO M. , BEHEIRY SALWA , NATALE ANDREA
Published: April 2007

Electroanatomic Mapping and Epicardial Ablation of VT. Endocardial radiofrequency catheter ablation of ischemic left ventricular tachycardia has been of variable success due to multiple factors. Two such factors include the location of the reentrant circuit in the deep myocardium or on the epicardial surface and the inherent limitations of fluoroscopy as a guide for target localization. We report a patient in whom successful epicardial mapping and radiofrequency catheter ablation of an ischemic left ventricular tachycardia was performed using pericardial access and the CARTO electroanatomic mapping system.
Connexins and Impulse Propagation in the Mouse Heart
Authors: JALIFE JOSÉ , MORLEY GREGORY E. , VAIDYA DHANANJAY
Published: April 2007

Connexins and Propagation. Gap junction channels are essential for normal cardiac impulse propagation. Three gap Junction proteins, known as connexins, are expressed in the heart: Cx40, Cx43, and Cx45. Each of these proteins forms channels with unique biophysical and electrophysiologic properties, as well as spatial distribution of expression throughout the heart. However, the specific functional role of the individual connexins in normal and abnormal propagation is unknown. The availability of genetically engineered mouse models, together with new developments in optical mapping technology, makes it possible to integrate knowledge about molecular mechanisms of intercellular communication and its regulation with our growing understanding of the microscopic and global dynamics of electrical impulse propagation during normal and abnormal cardiac rhythms. This article reviews knowledge on the mechanisms of cardiac impulse propagation, with particular focus on the role of cardiac connexins in electrical communication between cells. It summarizes results of recent studies on the electrophysiologic consequences of defects in the functional expression of specific gap junction channels in mice lacking either the Cx43 or Cx40 gene. It also reviews data obtained in a transgenic mouse model in which cell loss and remodeling of gap junction distribution leads to increased susceptibility to arrhythmias and sudden cardiac death. Overall, the results demonstrate that these are potentially powerful strategies for studying fundamental mechanisms of cardiac electrical activity and for testing the hypothesis that certain cardiac arrhythmias involve gap junction or other membrane channel dysfunction. These new approaches, which permit one to manipulate electrical wave propagation at the molecular level, should provide new insight into the detailed mechanisms of initiation, maintenance, and termination of cardiac arrhythmias, and may lead to more effective means to treat arrhythmias and prevent sudden cardiac death.
The Effect of Procainamide on T Wave Alternans
Authors: KAVESH NEAL G. , SHOROFSKY STEPHEN R. , SARANG SAMANTHA B. , GOLD MICHAEL R.
Published: April 2007

Procainamide and T‐Wave Alternans. Introduction: The measurement of microvolt level T wave alternans (TWA) is a technique for detecting arrhythmia vulnerability. Previous studies demonstrated that the magnitude of TWA is dependent on heart rate. However, the effects of antiarrhythmic drugs on TWA are unknown.

Methods and Results: This was a prospective evaluation of intravenous procainamide on TWA in 24 subjects with inducible sustained ventricular tachycardia (VT). Measurements of TWA were performed at baseline in the drug‐free state and after procainamide loading (1,204 ± 278 mg). Recordings were made in normal sinus rhythm, and during atrial pacing at 100 heats/min and 120 heats/min. The magnitude of TWA in the vector magnitude lead was decreased by procainamide at all heart rates: 0.6 ± 0.8 to 0.3 ± 0.4 μV in sinus rhythm, 2.0 ± 1.6 to 0.7 ± 0.7 μV at 100 beats/min, and 3.0 ± 2.0 to 1.7 ± 1.8 μV at 120 beats/min (P < 0.001 by analysis of variance). The sensitivity of TWA for the induction of VT at baseline was 5% in sinus, 60% at 100 beats/min, and 87% at 120 beats/min, while it decreased with procainamide to 5%, 19%, and 60%, respectively. Decreases in TWA in response to procainamide were independent of the antiarrhythmic effects on VT inducibility.

Conclusions: These results indicate that the magnitude of TWA decreases with acute procainamide loading and this effect decreases the sensitivity of TWA for the induction of sustained VT.
Separation Between Virtual Sources Modifies the Response of Cardiac Tissue to Field Stimulation
Authors: SUSIL ROBERT C. , A ERIC , TUNG LESLIE
Published: April 2007

Source Separation and Field Stimulation. Introduction: While it is now understood that the tissue geometry and the electric field distribution are important in generating virtual electrodes, the effects of interaction between a collection of electrodes have not been examined. To develop a basis for understanding such interactions, we have studied a single pair of oppositely polarized virtual sources. Although such oppositely polarized pairs of virtual electrodes can be generated by a variety of field distributions and tissue geometries, we examine one simple system that incorporates the salient features of source interaction.

Methods and Results: Our model system is a homogeneous tissue strip stimulated by a uniform extracellular field. To clarify virtual source interaction, we show that field stimulated tissue can be equivalently polarized by a set of intracellular current sources with magnitude and distribution defined by the generalized activating function. In our model system, an intracellular current source is produced at one edge of the tissue and an Intracellular current sink at the other. Therefore, the tissue length acts to modulate the overlap, or interaction, between the polarizations arising from each source. To quantify the effects of source interaction, the chronaxie and rheobase values of the strength‐duration relation were determined for source separations varying between 1.0 cm and 100 μm (active membrane dynamics were modeled with the Luo‐Rudy phase I formulation). At all separations > 3.0 mm, the chronaxie was constant at 3.09 msec and the rheobase was 0.38 V/cm. Under 0.2 mm, the chronaxie decreased to 0.55 msec while the rheobase increased linearly with the inverse of source separation. The dependence of these parameters on separation primarily reflects passive electrotonic interactions between the two virtual electrodes. However, the exact values are strongly dependent upon active tissue properties—largely the inward rectifier potassium channel and activation of the sodium current.

Conclusion: Tissue excitation in response to field stimulation is strongly modulated by the proximity of, and therefore the interaction between, oppositely polarized virtual electrode sources.
Electrophysiologic Study and Radiofrequency Catheter Ablation of Isthmus‐Independent Atrial Flutter
Authors: LAI LING‐PING , LIN JIUNN‐LEE , TSENG CHUEN‐DEN , STEPHEN HUANG SHOEI K.
Published: April 2007

Isthmus‐Independent Atrial Flutter. Introduction: We report the electrophysiologic study and radiofrequency catheter ablation of isthmus‐independent atrial flutter in 2 patients. The isthmus‐independent atrial flutter in these 2 patients had similar ECG and electrophysiologic findings. Both were reproducibly induced by rapid atrial pacing. The atrial activation sequence and entrainment study proved that these atrial flutters were not isthmus‐dependent. A high‐right atrial site was identified as the critical site of the slow conduction zone of the tachycardia in both. This site showed double potentials and mid‐diastolic potentials. Radiofrequency catheter ablation at this site successfully eliminated the isthmus‐independent atrial flutter in both patients.
Intraoperative Radiofrequency Ablation of Chronic Atrial Fibrillation: A Left Atrial Curative Approach by Elimination of Anatomic “Anchor” Reentrant Circuits
Authors: KOTTKAMP HANS , HINDRICKS GERHARD , HAMMEL DIETER , AUTSCHBACH RÜDIGER , MERGENTHALER JÖRG , BORGGREFE MARTIN , BREITHARDT GÜNTER , MOHR FRIEDRICH‐WILHELM , SCHELD HANS H.
Published: April 2007

Intraoperative Ablation of Atrial Fibrillation. Introduction: The percutaneous approach to radiofrequency (RF) catheter ablation for curative treatment of atrial fibrillation (AF) is an investigational technique, and the optimal composition of lesion lines is unknown. We tested an intraoperative RF ablation concept with elimination of left atrial anatomic “anchor” reentrant circuits.

Methods and Results: In 12 patients with an indication for valve surgery and chronic AF, a right atrial‐transseptal approach was chosen for access to the left atrium. AF had been present for 4.3 ± 3.9 years; the left atria measured 56 ± 7 mm. Under direct vision, contiguous lesion lines were placed endocardially with temperature‐guided RF energy applications for treatment of AF with a specially designed probe. The lesion lines were placed between the mitral annulus and the left lower pulmonary vein, further to the left upper pulmonary vein, from there to the right upper pulmonary vein, and finally to the right lower pulmonary vein. The antiarrhythmic ablation procedure lasted 19 ± 4 minutes. One patient died postoperatively of low cardiac output. During follow‐up of 11 ± 6 months, chronic AF was ablated successfully in 9 of 11 patients (82%). Six patients were in stable sinus rhythm or intermittent pacemaker rhythm, and three patients were in sinus rhythm with intermittent atypical atrial flutter.

Conclusions: Intraoperative RF energy application for induction of contiguous lesion lines is feasible. Elimination of anatomically defined “anchor” reentrant circuits within the left atrium prevented chronic AF in > 80% of the patients treated. Intraoperative validation of lesion line concepts for curative treatment of AF may he transferred to percutaneous ablation techniques.
Muscarinic Receptor Stimulation with Edrophonium Hydrochloride Does Not Elevate Ventricular Fibrillation Thresholds in Humans
Authors: MITRANI RAUL D. , KLOOSTERMAN E. MARTIN , HUIKURI HEIKKI , DYLEWSKI JOHN , ATAPATTU SURESH , INTERIAN ALBERTO , CASTELLANOS AGUSTIN , MYERBURG ROBERT J.
Published: April 2007

Edrophonium Hydrochloride Effect on VE Threshold. Introduction: Although decreased vagal tone, as measured by heart rate variability is a risk factor for ventricular fibrillation (VF) and sudden cardiac death, it is unknown whether increasing vagal tone has an antiarrhythmic effect. The purpose of this study was to determine whether edrophonium hydrochloride (HCl), a vagomimetic agent, increases VF threshold.

Methods and Results: Twenty‐eight consecutive patients with previously implanted defibrillators had two inductions of VF by monophasic direct‐current shocks delivered at 10 to 30 msec after the T wave peak, escalating energies (0.4, 1, then 3 J) until VF was induced. If VF was not induced, this protocol was repeated at the T wave peak and then at 10 to 30 msec before the T wave until VF was induced. Patients were randomized to receive edrophonium HCl (12 to 18 mg) or no drug before repeating the protocol for the second VF induction. The mean sinus cycle length increased from 782 to 872 msec in the group receiving edrophonium HCl (P = 0.006). In the control group, the mean sinus cycle length remained unchanged (838 vs 858 msec). The mean energy to induce VF, coupling interval relative to the T wave, and the number of attempts to induce VF were not different between VF induction attempts 1 and 2, and they were not different between the group receiving edrophonium HCl and the control group.

Conclusion: In a sedated patient population with implantable defibrillators, edrophonium HCl infusion prolongs sinus cycle length but does not change inducibility of VF using T wave shocks.
Block of HERG Potassium Channels by the Antihistamine Astemizole and its Metabolites Desmethylastemizole and Norastemizole
Authors: ZHOU ZHENGFENG , VORPERIAN VICKEN R. , GONG QIUMING , ZHANG SHETUAN , JANUARY CRAIG T.
Published: April 2007

Electrophysiologic Effects of Astemizole Metabolites.Introduction: The selective H1‐receptor antagonist astemizole (Hismanal) causes acquired long QT syndrome. Astemizole blocks the rapidly activating delayed rectifier K+current IKrand the human ether‐a go‐go‐related gene (HKRG) K+channels that underlie it. Astemizole also is rapidly metabolized. The principal metabolite is desmethylastemizole, which retains H1‐receptor antagonist properties, has a long elimination time of 9 to 13 days, and its steady‐state serum concentration exceeds that of astemizole by more than 30‐fold. A second metabolite is norastemizole, which appears in serum in low concentrations following astemizole ingestion and has undergone development as a new antihistamine drug. Our objective in the present work was to study the effects of desmethylastemizole, norastemizole, and astemizole on HERG K+channels.

Methods and Results: HERG channels were expressed in a mammalian (HEK 293) cell line and studied using the patch clamp technique. Desmethylastemizole and astemizole blocked HERG current with similar concentration dependence (half‐maximal block of 1.0 and 0.9 nM, respectively) and block was use dependent. Norastemizole also blocked HERG current; however, block was incomplete and required higher drug concentrations (half‐maximal block of 27.7 nM).

Conclusions: Desmethylastemizole and astemizole cause equipotent block of HERG channels, and these are among the most potent HERG channel antagonists yet studied. Because desmethylastemizole becomes the dominant compound in serum, these findings support the postulate that it becomes the principal cause of long QT syndrome observed in patients following astemizole ingestion. Norastemizole block of HERG channels is weaker; thus, the risk of producing ventricular arrhythmias may be lower. These findings underscore the potential roles of some H1‐receptor antagonist metabolites as K+channel antagonists.
Management of Vasovagal Syncope
Authors: ATIGA WALTER L. , ROWE PETER , CALKINS HUGH
Published: April 2007

Management of Vasovagal Syncope. Vasovagal syncope is a common disorder of autonomic cardiovascular regulation that can be very disabling and result in a significant level of psychosocial and physical limitations. The optimal approach to treatment of patients with vasovagal syncope remains uncertain. Although many different types of treatment have been proposed and appear effective based largely on small nonrandomized studies and clinical series, there is a remarkable absence of data from large prospective clinical trials. However, based on currently available data, the pharmacologic agents most likely to be effective in the treatment of patients with vasovagal syncope include beta blockers, fludrocortisone, and alpha‐adrenergic agonists. In this article, we provide a summary of the various therapeutic options that have been proposed for vasovagal syncope and review the clinical studies that form the basis of present therapy for this relatively common entity.
Sudden Death in Recipients of Transvenous Implantable Cardioverter Defibrillator Systems:
Authors: PIRES LUIS A. , HULL MICHAEL L. , NINO CHARLES L. , MAY LYNETTE M. , GANJI JAGADEESH R.
Published: April 2007

Sudden Death in ICD Recipients. Introduction: Transvenous implantable cardioverter defibrillator (ICD) systems are very effective in preventing sudden death; however, little is known about terminal events and potential causes and mechanisms of sudden death in recipients of these devices.

Methods and Results: We analyzed 74 cases of sudden death among patients enrolled in several clinical investigations of transvenous ICD systems. Eighty‐one percent were men (mean age 68 ± 10 years), 86% had coronary artery disease, mean left ventricular ejection fraction was 0.27 ± 0.11, and two thirds presented with sustained ventricular tachycardia. The final event was witnessed in 65 patients (81%). Based on reported ICD shocks, documented rhythm, and/or postmortem device data, sudden death was deemed tachyarrhythmic in 49 cases (66%), non‐tachyarrhythmic in 12 (16%), and indeterminate in the remaining 13 (18%). Multivariate analysis of several clinical and nonclinical factors found advanced age (>65 years, P = 0.03, odds ratio [OR] 1.75, 95% confidence interval [CI] 1.05 to 2.92), reduced left ventricular ejection fraction (< 0.35, P < 0.01, OR 3.51, CI 1.66 to 7.40), and having antibradycardia pacing ICDs (P = 0.02, OR 5.26, CI 1.37 to 20.0) to be independent predictors of sudden death. One or more predisposing factors and/or potential causes of sudden death were identified in 21 patients (28%).

Conclusion: In this select group of transvenous ICD recipients, (1) sudden death was associated with ventricular tachycardia/ventricular fibrillation in at least two thirds of cases, (2) nearly one third of patients had one or more factors, some device related, that could have been associated with sudden death, and (3) death ensued despite appropriate ICD therapies and, in many cases, external resuscitation, suggesting acute adverse events as common terminal factors.
ESCWGA/NASPE/P Experts Consensus Statement:
Authors: COSÍO FRANCISCO G. , ANDERSON ROBERT H. , KUCK KARL‐HEINZ , BECKER ANTON , BENDITT DAVID G. , BHARATI SAROJA , BORGGREFE MARTIN , CAMPBELL RONALD W.F. , GAITA FIORENZO , GUIRAUDON GERARD M. , HAÏSSAGUERRE MICHEL , KLEIN GEORGE , LANGBERG JONATHAN , MARCHLINSKI FRANCIS , RUFILANCHAS JUAN J. , SAKSENA SANJEEV , THIENE GAETANO , WELLENS HEIN JJ.
Published: April 2007

Anatomic Nomenclature of the AV Junctions. Current nomenclature for the AV junctions derives from a surgically distorted view, placing; the valvar rings and the triangle of Koch in a single plane with anteroposterior and right‐left lateral coordinates. Within this convention, the aorta is considered to occupy an anterior position, whereas the mouth of the coronary sinus is shown as being posterior. Although this nomenclature has served its purpose for the description and treatment of arrhythmias dependent on accessory pathways and AV nodal reentry, it is less than satisfactory for the description of atrial and ventricular mapping. To correct these deficiencies, a consensus document has been prepared by experts from the Working Group of Arrhythmias of the European Society of Cardiology and from the North American Society of Pacing and Electrophysiology. It proposes a new, anatomically sound, nomenclature that will be applicable to all chambers of the heart. In this report, we discuss its value for description of the A V junctions and establish the principles of this new nomenclature.
Effect of the Implantable Atrial Defibrillator on the Natural History of Atrial Fibrillation
Authors: TSE HUNG‐FAT , LAU CHU‐PAK , YU CHEUK‐MAN , LEE KATHY L.F. , MICHAUD GREGORY F. , KNIGHT BRADLEY P. , MORADY FRED , STRICKBERGER S. ADAM
Published: April 2007

Implantable Atrial Defibrillator. Introduction: The purpose of our study was to evaluate the effect of repeated cardioversion with an implantable atrial defibrillator on the clinical outcome of patients with atrial fibrillation.

Methods and Results: The effects of the implantable atrial defibrillator on the total duration of atrial fibrillation, number of atrial fibrillation recurrences, and left atrial size were evaluated prospectively in 16 patients with atrial fibrillation (13 men and 3 women; mean age 58 ± 11 years). Seven patients bad no cardiovascular disease, 5 patients had hypertension. 3 patients had coronary heart disease, and 1 patient bad congenital heart disease. Eight patients had paroxysmal atrial fibrillation for a mean duration of 80 ± 61 months, and eight patients had persistent atrial fibrillation for a mean duration of 68 ± 119 months. Except for one patient who received digoxin throughout the study, alt patients received the same Class I or III antiarrhythmic agent throughout the study. The implantable atrial defibrillator successfully converted 50 (93%) of 54 spontaneous episodes of atrial fibrillation in 12 patients. During the initial 3 months of clinical follow‐up, the atrial defibrillator documented 261 ± 270 hours of atrial fibrillation compared with 126 ± 172 hours (P = 0.01) during the subsequent 3 months. The left atrial size decreased from 4.4 ± 0.7 cm at the time of atrial defibrillator implantation to 4.1 ± 0.6 cm (P = 0.02) 6 months later. The number of atrial fibrillation recurrences did not change. These findings were observed in the absence of changes in drug therapy. No complications were observed.

Conclusion: Restoration and maintenance of sinus rhythm in patients with atrial fibrillation by repeated cardioversion with an implantable atrial defibrillator was associated with a reduction in the total arrhythmia duration and a reduction in left atrial size. These results suggest that maintenance of sinus rhythm with the atrial defibrillator may reverse the remodeling process associated with atrial fibrillation.
Differing Rate Dependence and Temporal Distribution of Repolarization Alternans in Patients with and without Ventricular Tachycardia
Authors: NARAYAN SANJIV M. , SMITH JOSEPH M.
Published: April 2007

Temporal Dynamics of Repolarization Alternans. Introduction: Repolarization atlternans(RPA) may reflect repolarization heterogeneities underlying VT, yet its temporal dynamics are poorly understood. We hypothesized (hat RPA occurring late, rather than early, with in repolarization reflects a temporal variation in recovery that may predispose to wave front fractionation and the initiation of reentrant VT, and that this temporal distribution may vary with heart rate.

Methods and Results: ECG leads I, aVF, and V1 were recorded in 40 patients during; electrophysiologic study. RPA across the JT interval was computed. spectrally for 64‐heatsequences at paced cycle lengths (CLs) of 600, 500, and 400 msec, and expressed as the T wave alternans ratio (TWAR) on the vector ECG lead. Significant RPA (TWAR ≥ 3) was reconstructed into the time domain, and its center of area used to represent its temporal distribution. Twenty‐two patients were inducible into VT and 18 were not. RPA was of larger magnitude in Inducible than noninducible patients (TWAR = 11.1 vs 4.42, P = 0.035; 38.3 vs 5.74, P = 0.004;and 88.8 vs 4.2S. P = 0.001 in each, respectively), and was distributed later (P < 0.02; CL 600msec). Applying TWAR ≥ 3 to the distal half of the JT segment produced greater specificity for inducible VT (88.9%, 66.7%, and 69.2% at each CL, respectively) than did RPA of the entire JT segment (77.8%. 53.3%, and 69.2%)

Conclusion: RPA is more specific for inducible VT when distributed late rather than else wherein repolarization, and this temporal distribution is heart rate sensitive. Further study is required to interpret these findings in the context of temporal dispersion of refractoriness.
Left Ventricular Ischemia due to Coronary Stenosis as an Unexpected Treatable Cause of Paroxysmal Atrial Fibrillation
Authors: SCHOONDERWOERD BAS A. , VAN GELDER ISABELLE C. , CRIJNS HARRY J.G.M.
Published: April 2007

Ischemia‐Related Paroxysmal Atrial Fibrillation. We present a patient with exercise‐induced paroxysmal atrial fibrillation who was eventually scheduled for a Cox‐maze operation due to persistence of his complaints of fatigue, impaired exercise tolerance, and predominantly exercise‐related irregular palpitations despite treatment with several antiarrhythmic drugs. A preoperative exercise stress test without antiarrhythmic or negative chronotropic drugs, however, showed clear evidence of myocardial ischemia. After coronary angioplasty of a significant stenosis in the left anterior descending artery, there was no recurrence of atrial fibrillation during a follow‐up of 7 months.
Review of Mechanisms by Which Electrical Stimulation Alters the Transmembrane Potential
Authors: NEWTON JONATHAN C. , KNISLEY STEPHEN B. , ZHOU XIAOHONG , POLLARD ANDREW E. , IDEKER RAYMOND E.
Published: April 2007

Transmembrane Potential Changes with Stimulation. Electrical stimuli pace, cardiovert, or defibrillate the heart by changing transmembrane potential (δVm). Recent simulation studies provide insights into mechanisms by which stimuli establish δVm. This review attempts a nonmathematical description of these mechanisms. We start with the cable model in which the intracellular core conductor is bounded by a highly resistive and capacitive membrane that separates the intracellular and extracellular spaces. Intracellular and extracellular resistances are assumed to vary linearly with position. Although this model predicts anodal extracellular stimuli hyperpolarize adjacent tissue and cathodal extracellular stimuli depolarize that tissue, it fails to reproduce regions of opposite δVm distant from the electrodes. We then consider the sawtooth model in which microscopic discontinuities in intracellular resistance represent gap junctions. While model studies with such discontinuities demonstrate large δVm at cell ends, experimental validation of such δVm remains elusive. Extending the analysis to the two‐ and three‐dimensional syncytium, we also consider the bidomain model in which intracellular, extracellular, and interstitial currents are explicitly characterized. Differences in resistance to these currents gives rise to virtual electrodes, which are experimentally observed regions of large δVm that arise distant from the stimulating electrode. Distant δVm regions are also evident when macroscopic discontinuities in intracellular resistance are introduced into the bidomain model. Such discontinuities are associated with clefts or scars that give rise to “secondary sources.” Albeit the cable model offers remarkable insight the bidomain model and the concept of secondary sources provide a more complete understanding of membrane excitation, especially when combined into a unifying activating function.