bluuebunny/crossref_metadata_2025 huggingface dataset:
Conduction Defects and Arrhythmias in Chagas' Disease:
Authors: DE CARVALHO ANTONIO C. CAMPOS , MASUDA MASAKI O. , TANOWITZ HERBERT B. , WITTNER MURRAY , GOLDENBERG REGINA C.S. , SPRAY DAVID C.
Published: May 2007

Gap Junctions and Humoral Factors in Chagas’ Disease. The protozoan parasite Trypanosoma cruzi causes Chagas’ disease, a major cause of cardiac dysfunction in Latin Americans. Chagas’ disease exhibits both acute and chronic phases, and each may be characterized by cardiac conduction disturbances. In acutely infected cultures of rodent heart cells, synchronized spontaneous beating becomes less regular, and coupling between cells is reduced. The basis of this decreased conduction is apparently in localization of the gap junction protein (Cx43) inside infected cells. Although total Cx43 is normal in infected cells, little is recognizable at appositional membranes. Electrophysiological properties are also altered by this infection. Action potentials are shortened, resting Ca2+ levels are elevated, and response to α‐adrenergic agonists was altered, compared to controls. Humoral factors may contribute to the conduction defects in chronic Chagas’ disease. Sera from chronically infected rabbits produced KC(J abnormalities in Langendorff‐perfused rabbit hearts. These findings indicate that chagasic infection may modify ion channel function in the heart, and we suggest that these changes may be manifested in the conduction disturbances that characterize this disease.
Impulse Formation and Conduction of Excitation in the Atrioventricular Node
Authors: WATANABE YOSHIO , WATANABE MARI
Published: May 2007

AV Nodal Conduction. Meijler et al. have recently challenged the classical concept of AV nodal conduction (the conduction hypothesis) and suggest that the AV node might he controlling ventricular rhythmicity through its automaticity electrotonically modulated In atrial excitation (the modulated pacemaker hypothesis). This article critically evaluates the three major arguments of Meijler: (1) the absence of convincing evidence for conduction of excitation in the AV node; (2) the prevalence of disproportionately short AV intervals in larger animals; and (3) elimination of KR intervals shorter than the cycle length of ventricular pacing during atrial fibrillation, to judge which of these two hypotheses would more satisfactorily explain various experimental and clinical findings accumulated in the past. Previous observations including microelectrode mapping of the rabbit AV junction during regular sinus rhythm as well as second–degree AV block, clinical and experimental studies on concealed conduction, and studies on the ventricular response to atrial fibrillation appear to he compatible with the conduction hypothesis, whereas clearcut evidence for automatic impulse formation in the AV node has not been presented, except in a small number of hearts showing spontaneous AV junctional rhythms. In view of these observations and theoretical considerations based on comparative anatomy of the AV node–His–Purkinje system and on the latest experimental study on the equine AV node, the authors conclude that the conduction hypothesis appears to better explain all the available data, except perhaps in a few cases with second–degree intra–AV nodal block.
Radiofrequency Catheter Ablation of Accessory Pathways:
Authors: HAÏSSAGUERRE MICHEL , GAÏTA FIORENZO , MARCUS FRANK I. , CLÉMENTY JACQUES
Published: May 2007

RF Catheter Ablation of APs. Catheter ablation techniques are now advocated as the first line of therapy for arrhythmias caused by accessory pathways (APs). The most common energy source is radiofrequency current, but technical characteristics vary. Several parameters can be used to determine the optimal target site: AP potential, AV time, atrial or ventricular insertion site, or unipolar morphology. Specific considerations are needed depending on AP location. Despite the different approaches described, there is no significant difference in the reported success rate, which is over 90%. However, the number of radiofrequency applications needed to achieve ablation appears to differ significantly, with median values from 3 to 8 reported. A combination of criteria related to both timing and direction of the activation wave‐front or use of subthreshold stimulation could improve the accuracy of mapping. In patients with “resistant” APs, different changes in ablation technique must be considered during the procedure to achieve elimination of AP conduction. The incidence of complications in multi‐center reports is close to 4%, with a recurrence rate of 8%. The long‐term safety of catheter ablation requires further study.
Clinical and Electrophysiologic Features of Syncope in Chronic Chagasic Heart Disease
Authors: FILHO MARTINO MARTINELLI , SOSA EDUARDO , NISHIOKA SILVANA , SCANAVACCA MAURÍCIO , BELLOTTI GIOVANNI , PILEGGI FÜLVIO
Published: May 2007

Syncope in CCHD. Introduction: Syncope in patients with chronic Chagasic heart disease (CCHD) is a frequent hut poorly studied problem.

Methods and Results: Fifty‐three patients with CCHD and recurrent syncope were followed for 2 to 127 months. They were classified into the following groups: G‐I (n = 15) without inducible ventricular tachycardia (VT) and normal HV interval; G‐II (n = 17) with only inducible VT; G‐III (n = 11) with only an abnormal HV interval; and G‐IV (n = 10) with both an inducible VT and an abnormal HV interval. Empiric pharmacologic therapy was given in G‐I; pharmacologic therapy guided by electrophysiologic: study in G‐II; atrioventricular pacing in G‐III; and empiric pharmacologic with atrioventricular pacing in G‐IV. Age and sex were similar among groups; New York Heart Association Functional Class I symptoms were more prevalent (P = 0.0001) in G‐I. The ejection fraction by echocardiography was higher in G‐I (P = 0.01221. The density of premature ventricular complexes by Duller monitoring was similar among groups. The complexity of premature ventricular complexes by Holler was significantly higher in G‐II (P = 0.0270); this variable, analyzed from the exercise electrocardiogram, was not different among groups. All deaths were sudden, prevalence was higher in G‐II and absent in G‐III, and recurrence of syncope was similar among groups.

Conclusion: The most probable causes of recurrent syncope were VT (43%) with poor prognosis, and paroxysmal atrioventricular block (21%) with a favorable prognosis. Absence of congestive heart failure, complexity of premature ventricular complexes by Holler, and absence of intraventricular heart block showed statistical correlation with normal electrophysiologic study, inducible VT, and normal HV interval, respectively.
The Effects of Lidocaine on the Vulnerable Period During Ventricular Fibrillation
Authors: CHA YONG‐MEI , PETERS BARRY B. , CHEN PENG‐SHENG
Published: May 2007

Vulnerability in Ventricular Fibrillation. Introduction: It was postulated that a subthreshold defibrillation shock failed to halt ventricular fibrillation because the shock itself reinitiated Ventricular fibrillation by falling into the vulnerable period of the wave fronts. Whether or not the timing of the vulnerable period is determined by the ventricular fibrillation cycle length is unknown.

Methods and Results: We determined the patterns of epicardial activation in ten dogs by computerized mapping techniques during unsuccessful defibrillation. Lidocaine was then given to prolong the ventricular fibrillation cycle length, and the computerized mapping studies were repeated. The results showed that lidocaine increased the ventricular fibrillation cycle length from 110 ± 13 msec to 156 ± 5 msec (P < (0.001). Among 55 episodes of unsuccessful defibrillation, the site of the earliest postshock activation occurred in the center of the mapped tissue 12 times at baseline and 14 times during lidocaine infusion. At electrodes that registered as post‐shock early sites, the preshock intervals clustered within a narrow range both before (58 ± 14 msec) and during (10l ± 18 msec, P < 0.001) lidocaine infusion. The correlation between the preshock intervals and the ventricular fibrillation cycle length was significant for these 26 sites (r = 0.87, P< 0.001.).

Conclusion: We conclude that a vulnerable period is present during ventricular fibrillation, and the timing of the vulnerable period is determined by the ventricular fibrillation cycle length.
Characterization of Shock‐Induced Action Potential Extension During Acute Regional Ischemia in Rabbit Hearts
Authors: KNISLEY STEPHEN B. , HOLLEY LORAINE K.
Published: May 2007

Shock Effects During Ischemia. Introduction: Defibrillation shocks produce extension of the myocardial action potential repolarization time (AP extension) in nonischemic myocardium. AP extension may synchronize repolarization in the heart because the extension increases when shock timing is increased. We tested whether AP extension occurs and whether it increases when shock timing is increased in regionally ischemic isolated perfused rabbit hearts stained with the transmembrane voltage sensitive fluorescent dye, di‐4‐ANEPPS and given diacetyl monoxime to eliminate motion artifacts.

Methods and Results: Before and after left anterior descending (LAD) coronary artery occlusion, APs were recorded on the anterior left ventricular epicardium with an epifluorescence measurement system. Hearts were paced with a train of 10 stimuli (SI) and then during the 10th AP were given a defibrillation shock (S2) from epicardial electrodes on either side of the recording region. Before LAD occlusion, duration of the 9th SI‐induced AP measured at full repolarization was 171 ± 11 msec (mean ± SD). Within 15 minutes after LAD occlusion, the AP duration became shorter (P < 0.05) and more variable (137 ± 42 msec), and APs with negligible plateaus were observed. Extension of the 10th AP by S2 was significant both before (mean extension of 59 to 65 msec for three S2 waveforms tested) and after LAD occlusion (mean extension of 35 to 41 msec). Unlike the results before LAD occlusion, AP extension after occlusion was independent of absolute shock timing expressed in msec. When timing was expressed as a fraction of individual AP durations, AP extension after occlusion increased with increases in shock timing.

Conclusions: Shocks extend Aps during ischemia; however, absolute time dependence of AP extension is not constant among cells that have different AP durations during Ischemia. This may influence postshock repolarization synchrony when different AP durations exist in different parts of regionally ischemic hearts.
Slowly Recovering Cardiac Sodium Current in Rat Ventricular Myocytes: Effects of Conditioning Duration and Recovery Potential
Authors: SHANDER GREGG S. , FAN ZHENG , MAKIELSKI JONATHAN C.
Published: May 2007

Slow Recovery of INa. introduction: Recovery of the Na channel from inactivation is essential to the normal conduction and refractoriness of the myocardium. In addition to fast recovery, occurring within several milliseconds at hyperpolarized potentials, a component of the current exhibits slow recovery occurring over hundreds of milliseconds. Long conditioning depolarizations potentiate slow recovery.

Methods and Results: This study was designed to test conditioning durations (tc) between 0.25 and 4 seconds (s) as to whether recovery was slowed by an effect on the fast (τt) and slow (τs) time constants of recovery, the relative amplitude of the slow component (As), or both. We studied Na channel recovery at ‐150 mV from inactivation using whole cell voltage clamp of rat ventricular cells at 23°C using a two‐pulse recovery protocol. Longer conditioning durations dramatically increased As, (from 12% for tc= 500 msec to 37% for tc= 4(MM) msec, P < 0.01). Neither τt (6 vs 5 msec) nor τs, (115 vs 140 msec) were significantly affected. In a second set of experiments, the recovery potential was depolarized to a potential at which the sodium current was 70% available (≅‐105 mV). This recovery potential had no significant effect on As, but both τf and τs were significantly slower (e.g., at tc= 2s, τs= 147 msec and As, = 28% at Vr= ‐150 mV, and τs, = 456 msec and As, = 29% at Vr, ≅ ‐105 mV). In addition, a 1‐ to 2‐msec lag in the onset of recovery was prominent at the depolarized recovery potentials.

Conclusions: Our results support a model for slow recovery where conditioning duration determines entry into an inactivated state from which Na channels recover slowly, and recovery potential determines the rate of recovery from this state. A kinetic scheme with at least three inactivated states is proposed. These results also have implications for cardiac excitability under conditions, such as ischemia, where membranes are depolarized.
Intermittent Preexcitation and Mesothelioma of the Atrioventricular Node: A Hitherto Undescribed Entity
Authors: BHARATI SAROJA , BAUERNFEIND ROBERT , JOSEPHSON MARK
Published: May 2007

Mesothelioma of AV Node with WPW. This is the first documented case of spontaneous intermittent preexcitation associated with mesothelioma of the atrioventricular (AV) node. A 66‐year‐old male with recurrent atrial arrhythmias, palpitations, heart failure, and marked intra‐atrial conduction defect that required a pacemaker died during sleep. Electrophysiologic study revealed left free‐wall bypass tract with marked intra‐atrial conduction defect and prolonged conduction across the bypass tract. With atrial pacing, high degrees of block were noted in the bypass tract. Serial section of the conduction system and both AV rims revealed two left posterior and lateral bypass pathways with patchy areas of fibrosis. A large mesothelioma (benign AV nodal tumor) almost completely replaced the AV node. In addition, there was marked fatty infiltration of the atria. In summary: (1) the intermittent preexcitation with prolonged conduction across the bypass tract and block with atrial pacing were probably related to the incomplete patchy degenerative changes in the bypass tract, and/or almost complete replacement of the AV node by the tumor; (2) the intra‐atrial conduction defect was probably related to the replacement of the AV node by mesothelioma and/or the fatty infiltration of the atria: and (3) the paroxysmal atrial arrhythmias probably reflect the marked atrial pathology.
Future Ablation Concepts of Tachyarrhythmias
Authors: CHEN SHIH‐ANN , CHIANG CHERN‐EN , TAI CHING‐TAI , LEE SHIH‐HUANG , CHANG MAU‐SONG
Published: May 2007

Catheter Ablation. Application of radiofrequency energy to arrhythmogenic substrates after careful cardiac mapping could ensure a high success rate in eliminating certain types of tachyarrhythmias. Future studies of catheter ablation will focus on how to improve ablation efficacy and achieve a better result in various types of tachyarrhythmias. More information about the arrhythmogenic mechanisms will be provided to improve the knowledge of diagnostic and interventional electrophysiology.
Cardiac Arrhythmias and Antiarrhythmic Drugs: Recent Advances in Our Understanding of Mechanism
Authors: ROSEN MICHAEL R.
Published: May 2007

Cardiac Arrhythmia Therapy. The purpose of this review is to consider our understanding of the mechanisms of action of cardiac antiarrhythmic drugs, as well as the status of our comprehension of arrhythmias and their therapy. The approach will be to review the basis for normal electrical activity of the heart, the mechanisms for cardiac arrhythmias, and our understanding of the mechanisms of drug action, and to distill from these strategies for the future. Immediate strategies in the prevention and treatment of life‐threatening arrhythmias will most likely continue to make use of catheter and electrically based therapy, but the longterm treatment of large populations of individuals will still require the search for, and testing and administration of, pharmacologic therapy. It is emphasized that simplistic approaches to the solution of the complex problem of arrhythmias and their management will probably continue to cause problems, and that only by mastering the complexities of pathophysiology may success be best assured.
Parenteral Antiarrhythmics for Life‐Threatening Ventricular Arrhythmias
Authors: FILART ROLAND A. , RIALS SETH J. , MARINCHAK ROGER A. , KOWEY PETER R.
Published: May 2007

Parenteral Antiarrhythmics for Ventricular Arrhythmias. The acute management of life‐threatening ventricular tachyarrhythmias often includes the use of parenteral antiarrhythmics. There are a number of agents currently available for this purpose. They are used to suppress inducible monomorphic ventricular tachycardia during programmed electrical stimulation, they terminate spontaneous sustained ventricular tachycardia, and prevent ventricular fibrillation in the setting of an acute myocardial infarction. Serious adverse reactions include proarrhythmia, hypotension, severe bradyarrhythmias, and precipitation of congestive heart failure. A comparative evaluation of intravenous antiarrhythmics is difficult due to inherent differences in the choice of agents for study, protocol design, patient population, defined endpoints, and serum drug levels. Likewise, the reported adverse reaction rates vary from 0.4% to 75%. To understand the difficulties in clinical decision‐making in this problem area, particularly drug selection, we present here a review of pertinent clinical trials evaluating parenteral drug efficacy and adverse effects.
Parenteral Antiarrhythmic Drug Therapy in Ventricular Tachycardia/Ventricular Fibrillation: Evolving Role of Class III Agents—Focus on Amiodarone
Authors: SCHEINMAN MELVIN M.
Published: May 2007

Intravenous Amiodarone. More effective intravenous antiarrhythmic agents are required for treatment of patients with refractory malignant ventricular arrhythmias. More recently, a great deal of interest has been focused on use of intravenous amiodarone for these patients. Uncontrolled early studies showed that intravenous amiodarone was effective in 42% to 81% of treated patients. Recent large cooperative trials have documented the efficacy of intravenous amiodarone in these patients and have shown an efficacy comparable to bretylium in patients with refractory sustained ventricular tachycardia or fibrillation.
Proarrhythmia with Class III Antiarrhythmic Drugs: Definition, Electrophysiologic Mechanisms, Incidence, Predisposing Factors, and Clinical Implications
Authors: HOHNLOSER STEFAN H. , SINGH BRAMAH N.
Published: May 2007

Proarrhythmia with Class III Antiarrhythmic Agents. Antiarrhythmic drugs can and do induce unexpected and sometimes fatal reactions by either producing new symptomatic arrhythmias or by aggravating existing arrhythmias. The definition of proarrhythmia has changed since controlled clinical studies showed a dichotomy between arrhythmia suppression and mortality. The nature of proarrhythmia reactions is linked to the electrophysiologic effects of various antiarrhythmic drugs. Whereas Class I agents without accompanying effects on repolarization generally produce ventricular tachycardia (often incessant) or fibrillation. Class III agents typically produce torsades de pointes that may deteriorate into ventricular fibrillation. The precise mechanism of torsades de pointes is not fully elucidated, although early afterdepolarization and increases in spatial or temporal dispersion of repolarization are likely possibilities. Proarrhythmic risk is lowest for amiodarone and is probably related to the drug's complex electrophysiologic profile. The incidence of torsades with sotalol increases with dose and the baseline values of the QT interval; the incidence with d‐sotalol and other pure Class III agents remains unclear. Prospective, randomized, placebo‐controlled studies to evaluate this are under way. The fact that d‐sotalol increases mortality in postinfarction patients suggests that it may possibly be a common property of most, if not all, pure Class III compounds. The ongoing clinical trials with various Class III agents are likely to provide the critical information on this important therapeutic issue.
Catheter Ablation for the Treatment of Paroxysmal Supraventricular Tachycardia
Authors: NACCARELLI GERALD V. , SHIH HUE‐TEH , JALAL SOHAIL
Published: May 2007

Catheter Ablation for PSVT. Radiofrequency catheter ablation has evolved into a front‐line curative therapy for patients who have paroxysmal supraventricular tachycardia secondary to Wolff‐Parkinson‐White syndrome, AV nodal reentrant tachycardia, and atrial tachycardia. In patients with accessory pathways, cure rates exceed 90% in almost all anatomic locations. Equally high success rates are noted in patients with atriofascicular pathways and the permanent form of junctional reciprocating tachycardia. Complications secondary to catheter ablation of accessory pathways occur in 1% to 3% of patients and include cardiac perforation, tamponade, AV block, and stroke. In patients with AV nodal reentrant tachycardia, selective slow pathway ablation is curative in over 95% of patients with a very low risk of AV block. Atrial tachycardias originating in both the left and right atria can he successfully ablated in over 80% of patients. Given the overall effectiveness of this procedure, radiofrequency catheter ablation should be considered as front‐line therapy in patients with recurrent or drug‐refractory paroxysmal supraventricular tachycardia. Although an effective therapy, the risks and benefits of this procedure need to be assessed in all patients who are candidates for this procedure.
Increased Propensity of Women to Develop Torsades de Pointes During Complete Heart Block
Authors: KAWASAKI RAYMOND , MACHADO CHRISTIAN , REINOEHL JOEL , FROMM BARBARA , BAGA JOHN J. , STEINMAN RUSSELL T. , LEHMANN MICHAEL H.
Published: May 2007

TdP and Complete Heart Block. Introduction: To determine whether an increased female gender susceptibility to torsades de pointes (TdP) may exist in a clinical model of bradycardia‐ induced long QT syndrome, we investigated reported cases of TdP associated with acquired complete heart block.

Methods and Results: Seventy‐two cases reported in the medical literature dating from 1941 through 1993 were identified, all describing TdP or “transient ventricular tachycardia/fibrillation” (to include those cases reported prior to the use of TdP terminology) in the setting of acquired complete heart block unassociated with QT prolonging drugs. Expected female prevalence in complete heart block was estimated at 52%, based on projections derived from 206,016 hospital discharges in the National Inpatient Profile (Commission on Professional and Hospital Activities, Ann Arbor, MI), over the years 1985 through 1992. During complete heart block, mean heart rate was 37 beats/min in both sexes (combined n = 43), and absolute QT interval ranged from 0.52 to 0.88 seconds, with a mean of 0.68 seconds (n = 25). Female prevalence among patients with TdP during complete heart block was greater than expected: 72% for all studied cases (P < 0.001); 70% (P < 0.04) and 74% (P < 0.02) among those reported prior to (n = 35) and during or alter (n = 37) 1980, respectively; 73% (P < 0.03) among those with documented normokalemia (n = 26); and 68% (P = 0.2) among those with a prolonged QT interval and known polymorphic VT (i.e., unequivocal TdP; n = 25).

Conclusion: Despite inherent limitations of this retrospective study, the data are consistent in suggesting a greater than expected female prevalence among patients with TdP related to complete heart block. This finding lends support to a broadening concept of increased susceptibility of women to the development of TdP in various settings of QT prolongation.
Radiofrequency Ablation of Atrial Insertion of Left‐Sided Accessory Pathways Guided by the “W Sign”
Authors: MANOLIS ANTONIS S. , WANG PAUL J. , ESTES N.A. MARK
Published: May 2007

AP Ablation and the “W Sign.”introduction: The aim of this study was to evaluate the efficacy of radiofrequency (RF) ablation of the atrial insertion of left‐sided aceessory pathways with guidance by a specific morphologic characteristic of the local electrogram, which we call the “W sign.” This represents the shortest local atrioventricular (AV) interval during sinus rhythm in patients with manifest preexcitation or the shortest local VA interval during AV reciprocating tachycardia and/or ventricular pacing in patients with concealed accessory pathways.

Methods and Results: The transseptal technique was used in 31 patients (18 men, 13 women; aged 32 ± 13 years), and RF ablation of 33 accessory pathways (26 manifest and 7 concealed) was attempted. Patients presented with palpitations (n = 16), presyncope (n = 10), or syncope (n = 5). The clinical arrhythmia was AV reciprocating tachycardia (n = 24) or atrial fibrillation (n = 7). In 21 patients (68%) electrophysiologic study and RF ablation were performed at a single session. Accessory pathways were left posteroseptal (n = 5) or left free wall (n = 28). The “W sign,” formed from merging of the local atrial and ventricular electrograms, was identified at all successful sites prior to ablation. Ablation was successful in all patients. A median of 7 RF lesions were delivered per patient. The fluoroscopy time was 76 ± 48 minutes; total procedure time was 5.4 ± 1.9 hours. No significant complications occurred. Early recurrence (≤ 24 hours) occurred in I patient; during 6 ± 4 months, accessory pathway conduction recurred in another patient.

Conclusion: We conclude that RF ablation of the atrial insertion of left accessory pathways can be very successful when guided by the “W sign.”
Radiofrequency Ablation of Idiopathic Left Anterior Fascicular Tachycardia
Authors: BOGUN FRANK , El‐ATASSI RAFEL , DAOUD EMILE , MAN K. CHING , STRICKBERGER S. ADAM , MORADY FRED
Published: May 2007

Left Anterior Fascicular Tachycardia. Introduction: A 45‐year‐old man with idiopathic ventricular tachycardia (VT) having a right bundle branch block configuration with right‐axis deviation underwent au electrophysiologic test.

Methods and Results: Mapping demonstrated a site on the auterobasal wall of the left ventricle where there was an excellent pace map and an endocardial activation time of ‐20 msec, hut radiofrequency catheter ablation at this site was unsuccessful. At a nearby site, a presumed Purkinje potential preceded the QRS complex by 30 msec during VT and sinus rhythm, and catheter ablation was effective despite a poor pace map and an endocardial ventricular activation time of zero.

Conclusion: Idiopathic VT with a right bundle branch configuration and right‐axis deviation may originate in the area of the left anterior fascicle. A potential presumed to represent a Purkinje potential may he more helpful than endocardial ventricular activation mapping or pace mapping in guiding ablation of this type of VT.
Inappropriate Sinus Tachycardia: Evaluation and Therapy
Authors: KRAHN ANDREW D. , YEE RAYMOND , KLEIN GEORGE J. , MORILLO CARLOS
Published: May 2007

Inappropriate Sinus Tachycardia. Inappropriate sinus tachycardia is an ill‐defined clinical syndrome characterized by an increased resting heart rate accompanied by an exaggerated response to exercise or stress. It is not associated with underlying structural heart disease. The mechanism may involve a primary abnormality of the sinus node demonstrating enhanced automaticity or, alternatively, a primary autonomic disturbance with increase sympathetic activity and enhanced sinus node β‐adrenergic sensitivity. The diagnosis of inappropriate sinus tachycardia is one of exclusion. It is most common in young females, with a disproportionate number employed in the health care field. Autonomic and electrophysiologic testing may be required in selected individuals to clarify the mechanism and rule out sinus node reentry or right atrial tachycardia. Therapy of inappropriate sinus tachycardia is empiric. Pharmacologic approaches include beta blockers or verapamil. Radiofrequency catheter ablation of the superior portion of the sinus node shows promise as a useful alternative in patients with refractory symptoms.
Assessment of Pacing Maneuvers Used to Validate Anterograde Accessory Pathway Potentials
Authors: NIEBAUER MARK J. , DAOUD EMILE , GOYAL RAJ , HARVEY MARK , CASTELLANI MARK , BOGUN FRANK , CHAN K. KWOK , MAN K. CHING , STRICKBERGER ADAM , MORADY FRED
Published: May 2007

Validation of Accessory Pathway Potentials. Four pacing maneuvers have been proposed to validate an anterograde accessory pathway potential (APP): (1) atrial pacing to induce complete block between the atrial electrogram and the APP; (2) ventricular pacing to advance the APP without altering the timing of the atrial electrogram; (3) atrial pacing to induce complete block between the APP and the ventricular electrogram; and (4) ventricular pacing to advance the ventricular electrogram without altering the timing of the APP. The purpose of this study was to assess these validation techniques by applying them to electrograms that simulated APPs but which were known to be atrial in origin. In 32 patients undergoing an electrophysiology procedure, a split atrial electrogram containing two components separated by at least 30 msec (mean 54 ± 15 msec) was recorded. Using an atrial extrastimulus tecbnique, complete block between the two components of the atrial electrogram (criterion 1) could never be induced, but complete block between the second component of the atrial electrogram and the ventricular electrogram (criterion 3) consistently was induced. Using a ventricular extrastimulus technique, the second component of the atrial electrogram consistently could be advanced by 10 to 40 msec without altering the timing of the first component (criterion 2). In addition, with ventricular pacing, the ventricular electrogram consistently was advanced without altering the timing of the two components of the atrial electrogram (criterion 4). In conclusion, among the four pacing maneuvers used to validate an anterograde APP, the only one that may be specific for an APP is the ability to induce complete block between the atrial electrogram and the APP.
Calculation of Transmembrane Current From Extracellular Potential Recordings: A Model Study
Authors: LEON L. JOSHUA , WITKOWSKI FRANCIS X.
Published: May 2007

Transmembrane Current Estimation. Introduction: A mathematical/computer model of cardiac tissue was used to study the estimation of transmembrane current (EIm) from extracellular potential recordings.

Methods and Results: The simulated EIm of transmembrane current was compared with the simulated transmembrane current (Im), and both simulated values were compared with experimentally derived EIm obtained during sinus rhythm and ventricular fibrillation in dogs. We found that although EIm measurements slightly overestimate the duration of the Im waveform, they provide a reasonable approximation of Im during normal conduction and during decremental conduction and conduction block.

Conclusions: There is a very clear linear correlation between the time spent at or below 25% of the peak inward transmembrane current (Im25), its corresponding estimate (EI25), the peak inward Im and EIm and the peak ionic current, providing some evidence that EIm25 may be a suitable in vivo measure of peak ionic current.
Modulation of Connexin43 Expression:
Authors: DAVIS LLOYD M. , SAFFITZ JEFFREY E. , BEYER ERIC C.
Published: May 2007

Modulation of Cx43 Expression. Introduction: Gap junctions connect cardiac myocytes allowing propagation of action potentials. They contain intercellular channels formed by multiple different connexin proteins. The arrangement and type of gap junctions and the types, function, and interaction of connexin proteins determine intercellular resistance and can thereby influence conduction velocity and the potential for reentrant arrhythmias. Our goal was to develop genetically manipulable models to test the effects of altering expression of a major cardiac connexin (connexin43) on intercellular coupling and expression of other connexin proteins.

Methods and Results: BHK cells that are poorly coupled and BWEM ceils that are well coupled were stably transfected with plasmids containing connexin43 cDNA in antisense and sense orientations. RNA blots confirmed expression of the transfected transcripts. Immunoblots showed that connexin43 protein was reduced in the BHK antisense transfectants and increased in the BHK sense transfectants compared to the parental cells. It was not detectably changed in the BWEM antisense transfectant line compared to the BWEM parental cells. Transfection of connexin43 cDNA did not affect production of connexin45 mRNA and protein nor did transfection induce expression of other previously unexpressed connexin mRNAs. Cell coupling was assessed by intercellular diffusion of microinjected Lucifer yellow in confluent cell populations. Lucifer yellow passed to a mean of 3 ± 3 neighboring parental BHK cells, to 8 ± 8 neighbors in the sense connexin43 transfected BHK cells, and to only 2 ± 2 neighbors in the antisense connexin43 transfected BHK cells (P < 0.05). In contrast, dye transfer did not differ significantly between the parental BWEM cells (mean transfer = 19 ± 14 cells) and the BWEM connexin43 antisense transfectants (mean transfer = 15 ± 12 cells) (P = 0.20).

Conclusions: These data demonstrate that stable transfection with connexin43 cDNA constructs can result in detectable changes in connexin43 expression and cellular coupling without inducing compensatory changes in the cell's connexin phenotype and, therefore, may provide a basis for future attempts at specifically modulating connexin expression and intercellular resistance in cardiac tissues.
Wolff‐Parkinson‐White Syndrome Presenting as the Permanent Form of Junctional Reciprocating Tachycardia
Authors: ARRIBAS FERNANDO , LÓPEZ‐GIL MARÍA , NÚNEZ AMBROSIO , COSÍO FRANCISCO G.
Published: May 2007

Permanent Reciprocating Tachycardia and Preexcitation. The substrate of the permanent form of junctional reciprocating tachycardia is an accessory pathway with no spontaneous anterograde conduction, usually located in the posteroseptal area. We report a case of this type of tachycardia with overt anterograde ventricular preexcitation. Electrophysiologic study confirmed that tachycardia was due to an accessory pathway with long retrograde conduction time; electrophysiologic findings suggested longitudinal dissociation of the accessory pathway. Radiofrequency application at the coronary sinus os resulted in disappearance of preexcitation and cure of the tachycardia.
Effect of Sustained Load on Dispersion of Ventricular Repolarization and Conduction Time in the Isolated Intact Rabbit Heart
Authors: ZABEL MARKUS , PORTNOY STUART , FRANZ MICHAEL R.
Published: May 2007

Effect of Sustained Load on EP Parameters. Introduction: It is well known that myocardial stretch can elicit ventricular arrhythmias in experimental models. However, previous reports have predominantly documented stretch‐induced arrhythmias during short, pulsatile stretch. The arrhythmogenic mechanism of sustained static stretch is incompletely understood.

Methods and Results: To examine the influence of sustained load on several electrophysiologic parameters, a latex balloon was placed into the left ventricle of ten isolated Langendorffperfused rabbit hearts and filled with a neutral volume of fluid. The heart was paced from a catheter inside the right ventricle (apicoseptal endocardial position), and the following parameters were studied during steady‐state pacing with a cycle length of 500 msec (S1) and during extrastimulation (S2, base drive of 8 beats): monophasic action potential (MAP) durations at 90% repolarization (APD90) from 5 to 6 epicardial electrodes located on both ventricles and one right ventricular endocardial contact electrode; dispersion of APD90 (range of MAP durations from all electrodes); effective refractory period (ERP) and longest activation time (pacing stimulus to MAP upstroke). After baseline recordings, the balloon inside the left ventricle was filled with a volume of 1.0 mL of fluid by means of a servo‐controlled pump. The ERP was significantly shortened from 198 ± 9 msec at baseline to 183 ± 8 msec during sustained load (P < 0.03). Similarly, the average APD90 was shortened from 180 ± 5 msec at baseline to 175 ± 6 msec during sustained load (P < 0.006) with steady‐state pacing and from 178 ± 6 msec to 170 ± 8 msec during premature extrastimulation (P < 0.03). At the same time, dispersion of APD90 was increased from 27 ± 5 msec to 38 ± 6 msec (P < 0.002) during steady‐state pacing and from 28 ± 4 msec to 38 ± 6 msec (P = 0.013) during premature extrastimulation. The longest activation time among all MAP recordings was increased from 39 ± 2 msec to 43 ± 3 msec (P = 0.003) during steady‐state pacing and from 56 ± 6 msec to 69 ± 6 msec during premature extrastimulation (P < 0.003).

Conclusions: Sustained load shortens the ERP and the mean APD90 and at the same time increases dispersion of APD90 and prolongs activation times. These findings provide additional insight into the arrhythmogenic mechanisms of sustained mechanical load.
d‐Sotalol Decreases Defibrillation Energy Requirements in Humans:
Authors: DORIAN PAUL , NEWMAN DAVID , SHEAHAN RICHARD , TANG ANTHONY , GREEN MARTIN , MITCHELL JANET
Published: May 2007

d‐Sotalol and Defibrillation Energy. Introduction: We assessed the effect of d‐sotalol on defibrillation voltage and energy requirements in patients undergoing automatic defibrillator implantation. Drugs that primarily prolong cardiac refractoriness generally decrease the energy requirements for defibrillation in animal models. Despite the widespread use of antiarrhythmic drugs in patients with implanted cardioverter defibrillators, the effect of such drugs on defibrillation energy requirements in humans has not been well studied. Sotalol (in the d,l racemic form) is an antiarrhythmic with beta‐blocking and cardiac refractoriness prolonging effects. The d‐isomer of sotalol is largely devoid of beta‐blocking effects; both forms decrease defibrillation energy requirements in animals. We hypothesized that d‐sotalol would decrease defibrillation voltage and energy requirements in humans.

Methods and Results: Fifteen patients undergoing implanted cardioverter defibrillator implantation were studied before and 20 minutes after d‐sotalol infusion (2 mg/kg IV in 15 min, followed by 1 mg/kg per hour). The estimated energy (E50) and voltage (V50) for 50% success in defibrillation (estimated from two successive defibrillation “thresbold” measurements), ventricular effective refractory period, monopbasic action potential duration, and mean cycle length of ventricular fibrillation were measured, along with heart rate, blood pressure, and plasma concentration of d‐sotalol. There was a significant decrease in defibrillation energy (E50= 12.4 ± 5.0 J before and 8.4 ± 4.0 J after d‐sotalol, P < 0.003) and voltage (V50= 440 ± 77 V before and 354 ± 93 V after d‐sotalol, P < 0.001). Consistent with the Class III effect of d‐sotalol, ventricular effective refractory period increased from 284 ± 21 to 330 ± 24 msec (P < 0.001), and action potential duration was prolonged from 296 ± 28 to 340 ± 22 msec (P < 0.001). Following d‐sotalol, there was a tendency for induced tachyarrhythmia to self‐terminate (23/102 episodes before vs 74/150 after sotalol, P < 0.001), and ventricular fibrillation cycle length was increased from 216 ± 20 msec before to 274 ± 23 msec (P < 0.001) after d‐sotalol, despite the persistence of a rapid, disorganized rhythm of the surface ECG. No patient suffered adverse effects.

Conclusions: d‐Sotalol lowers defibrillation energy by a mean 32%± 27% at concentrations producing a 16%± 7% increase in ventricular effective refractory period. Along with its other antiarrhythmic effects, d‐sotalol may increase the safety margin for defibrillation or allow lower programmed energies in patients with implanted defibrillators.
The Signal‐Averaged Electrocardiogram:
Authors: STEINBERG JONATHAN S. , BERBARI EDWARD J.
Published: May 2007

Update on SAECG. The signal‐averaged electrocardiogram (SAECG) facilitates noninvasive recording of low‐amplitude cardiac signals such as ventricular late potentials. The SAECG has been used to accurately predict life‐threatening ventricular tachyarrhythmias in patients after acute myocardial infarction and with nonischemic dilated cardiomyopathy, and to screen for inducible ventricular tachycardia in patients with unexplained syncope and with nonsustained ventricular tachycardia. This review focuses on currently accepted methodology and clinical and research applications of the SAECG.
Bundle Branch Reentry Ventricular Tachycardia:
Authors: SARTER BRIAN H. , SCHWARTZMAN DAVID , CALLANS DAVID J. , GOTTLIEB CHARLES D. , MARCHLINSKI FRANCIS E.
Published: May 2007

Bundle Branch Reentry VT. We describe a patient with bundle branch reentry ventricular tachycardia with 1:1 VA conduction in whom resetting was performed while obtaining simultaneous recordings from the right ventricular apex (V) and His‐bundle electrogram. Both the tachycardia return cycle and the V‐His interval demonstrated an increasing reset response, while the His‐V interval demonstrated a flat reset response. These reset responses are consistent with a partially excitable gap localizing to the V‐His portion of the bundle branch reentry circuit.
Defibrillation Using a High‐Frequency Series of Monophasic Rectangular Pulses: Observations and Model Predictions
Authors: SWEENEY ROBERT J. , GILL ROBERT M. , JONES JANICE L. , REID PHILIP R.
Published: May 2007

High‐Frequency Defibrillation. Introduction: Capacitor‐discharge type waveforms are practical for defibrillation devices but may not be optimum. Discharging a capacitor as a series of high‐frequency (HF) pulses may allow effective waveform shaping by modulating the pulses. This approach could lead to improved defibrillation by allowing waveforms that would otherwise be unachievable with a capacitor‐discharge approach. However, little is known about defibrillation with HF.

Methods and Results: In open chest pentobarbital anesthetized dogs, we measured defibrillation thresholds for continuous rectangular waveforms with 5‐, 10‐, and 20‐msec durations and for 10‐ and 20‐msec long series of HF rectangular pulses. HF series bad a 50%“on‐time” duty cycle at 100 Hz to 20 kHz. At 1 kHz and above, defibrillation with HF required the same time‐averaged current but approximately twice the peak current and energy as defibrillation with continuous waveforms having the same envelope duration. At lower frequencies, defibrillation peak current and energy approached values required for the continuous waveforms. While waveforms were not actually filtered, the heart responded as though the HF series were low‐pass filtered. A filtered effective waveform model with a 3.7‐msec time constant predicts these HF data and makes reasonable predictions for various continuous waveform shapes.

Conclusion: Defibrillation is possible using HF pulses up to 20 kHz and has a frequency response similar to a low‐pass filter. A filtered effective waveform model predicts these HF results and may help explain bow waveforms influence defibrillation efficacy. While the unmodulated HF pulsing used in this study increased defibrillation requirements, these findings support the concept that HF pulse modulation can be used to change the effective shape of a waveform, which could permit more efficacious waveform shapes and a net reduction of thresholds.
Temperature‐controlled Radiofrequency Catheter Ablation of Accessory Pathways and Atrioventricular Nodal Reentrant Tachycardia: The 5‐French Catheter Approach
Authors: KOTTKAMP HANS , CHEN XU , HINDRICKS GERHARD , WICHTER THOMAS , WILLEMS STEPHAN , YLI‐MÄYRY SINNIKA , BREITHARDT GÜNTER , BORGGREFE MARTIN
Published: May 2007

Ablation with Temperature‐Controlled 5‐French Catheters. Introduction: In the present study, we assessed the feasibility of radiofrequency (RF) ablation of accessory pathways and AV nodal reentrant tachycardias with novel 5‐French catheters with 4‐mm tip electrodes using established mapping criteria and temperature‐controlled power output control.

Methods and Results: In this prospective study, 60 consecutive adult patients (mean age 36 ± 20 years) with accessory pathways (n = 37; 24 left‐sided) or AV nodal reentrant tachycardia (n = 23) underwent RF catheter ablation. A 5‐French catheter with a 4‐mm tip electrode and an embedded thermistor was used for RF application. The surface of the tip electrodes was 26 mm2 compared to 38 mm2 of 7‐French catheters with 4‐mm tip electrodes from the same catheter series. Power output was automatically and continuously adjusted according to the preset catheter tip temperature of 60° to 70°C. Pulse duration was 90 seconds. For left‐sided accessory pathways, the retrograde route via the femoral artery was used. After removing the 5‐French sheaths, only 4 hours of bed rest were advised. For ablation of AV nodal reentrant tachycardia, the so‐called slow pathway was targeted for ablation. Acute success was achieved in 34 (92%) of 37 patients with accessory pathways and 23 (100%) of 23 patients with AV nodal reentrant tachycardia. A mean of 3 ± 4 RF pulses (median 2 pulses; range 1 to 20 pulses) was applied. The mean fluoroscopy time was 26 ± 21 minutes. No complete AV block or other procedure‐related complications were observed. Recurrences occurred in 2 patients with accessory pathways and in 2 patients with AV nodal reentrant tachycardia during a follow‐up of 9 ± 4 months.

Conclusions: Temperature‐controlled RF ablation of accessory pathways and AV nodal reentrant tachycardia in adults using 5‐French catheters is feasible, effective, and safe. Ablation with 5‐French catheters might help to reduce the complication rate of catheter ablation techniques.
Phenylephrine‐Induced Ventricular Arrhythmias in Dogs with Inherited Sudden Death
Authors: MOÏSE N. SYDNEY , MOON PAULA F. , FLAHIVE WILLIAM J. , BRITTAIN DARCY , PRIDE H. PAUL , LEWIS BETH A. , ZIPES DOUGLAS P. , LEE RANDALL J. , GILMOUR ROBERT F.
Published: May 2007

Dogs with Inherited Sudden Death.Introduction:Dogs with an inherited predisposition to sudden death display ventricular arrhythmias having certain characteristics, such as pause dependence, that are suggestive of early afterdepolarization‐induced triggered activity. We hypothesized that α‐adrenergic stimulation may facilitate the development of these arrhythmias by inducing a reflex bradycardia and by exerting a direct myocardial effect.

Methods and Results:Twenty affected dogs and 7 unaffected dogs were studied. The incidence and severity of ventricular arrhythmias were determined after administration of phenylephrine (0.01 mg/kg IV), with or without pretreatment with propranolol (0.1 to 0.3 mg/kg IV), atropine (0.04 mg/kg IV), or prazosin (0.5 mg/kg IV). Third‐degree heart block was induced by AV nodal ablation in 4 affected dogs. Phenylephrine increased ventricular arrhythmias in affected dogs, with or without pretreatment with propranolol, but did not induce ventricular arrhythmias in unaffected dogs. In dogs with intact AV nodal conduction, atropine increased sinus rate, which suppressed baseline and phenylephrine‐induced arrhythmias. In dogs with heart block, arrhythmias were increased during baseline and after phenylephrine with or without pretreatment with atropine. Prazosin and overdrive ventricular pacing suppressed phenylephrine‐induced arrhythmias.

Conclusion:Phenylephrine increases ventricular arrhythmias in dogs with inherited sudden death via both an induction of reflex bradycardia and a direct myocardial effect. Superimposition of heightened α‐adrenergic and vagal tone may facilitate the development of sudden death in these animals.
Irregular Sinus Parasystole Due to Intermittency and Modulation of Parasystolic Activity
Authors: SATULLO GAETANO , DONATO ANTONINO , BUSÁ GIUSEPPE , CAVALLARO LUCIO
Published: May 2007

Intermittent Sinus Parasystole. A case of intermittent sinus parasystole in which the parasystolic focus is protected from the dominant sinus rhythm only during the second half of its intrinsic cycle is reported. In addition, a modulating (i.e., electrotonic) effect is often clearly exerted from the dominant rhythm upon the focus during the protected period. Coexistence of both modulation and intermittency in sinus parasystole, as well as a modulating effect limited to the second part of the parasystolic cycle, have not been previously reported.