bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Atrial Fibrillation and Appropriate Implantable Cardioverter Defibrillator Therapy:Results from a Prospective Study
Authors: GRÖNEFELD GERIAN C. , MAUSS OLIVER , LI YI‐GANG , KLINGENHEBEN THOMAS , HOHNLOSER STEFAN H.
Published: August 2003

Atrial Fibrillation and Appropriate ICD Therapy. Introduction: Atrial fibrillation(AF) is associated with significant morbidity and mortality that may be related to heniodynamic Impairment, thromboembolic events, or enhanced electrical instability of the ventricular myocardium. There is, however, a lack of data concerning the association of AF and ventricular tachyarrhythmias.

Methods and Results: Consecutive patients with indication for an implantable cardioverter defibrillator (ICD) were classified for the presence or absence of persistent AF at the time of device implantation. Incidence of device therapy, stored electrograms, and clinical events during follow‐up were evaluated prospectively. Two hundred fifty patients were included. During follow‐up (20 ± 14 months), patients in AF experienced appropriate device therapy for recurrent ventricular arrhythmias more frequently compared with patients in sinus rhythm (SR) (63% vs 38%, P = 0.01). On multivariate analysis, AF was an independent predictor of appropriate ICD therapy (relative risk 1.8; 95% confidence interval [CI] 1.2 to 2.9) and in appropriate device therapy (relative risk 2,3; 95% CI 1,2 to 4.5). Predefined clinical events (cluster endpoint: death, syncope, and hospitalizations) were observed more frequently in AF than in SR patients (55% vs 31%. P = 0.01). Analysis of device‐stored electrograms revealed a higher incidence of short‐long‐short cycles preceding ventricular arrhythmias in AF compared with SR patients (50% vs 16%, P = 0.002), Baseline heart rate preceding ventricular arrhythmias did not differ between the two groups.

Conclusion: AF is an independent predictor of recurrent ventricular arrhythmias in ICD recipients. The underlying electrophysiologic mechanism seems to be irregular rather than rapid ventricular activation, with a high incidence of short‐long‐short sequences preceding ventricular tachyarrhythmias in AF patients.
Estimation of Atrial Response to Entrainment Pacing Using Electrograms Recorded from Remote Sites
Authors: TRIEDMAN JOHN K. , ALEXANDER MARK E. , BERUL CHARLES L , BEVILACQUA LAURA M. , WALSH EDWARD P.
Published: August 2003

Determination of Entrainment Response. Introduction: Assessing the entrainment response by measuring pustpacing intervals (PPIs) at the pacing site facilitates localization of reentrant circuits, but may be technically difficult.

Methods and Results: There were 269 right atrial sites entrained in 21 circuits in congenital heart patients left atrial (LA) electrograms were recorded. Entrainment response was measured by two methods: (1) PPI‐tachycardia cycle length, and (2) the difference in latencies between the stimulus artifact and the pacing site electrogram, referenced to the LA electrogram. PPI also was measured from the LA as an index of antidromic activation. Among 43 pacing sites with antidromic LA activation, half showed a discrepancy ≥25 msec between methods 1 and 2. At the other 226 sites, agreement between the two methods was high (mean discrepancy ‐3 ± 8 msec, r = 0.975, 0 sites with discrepancy ≥25 msec). Correcting all sites by LA antidromicity reduced the mean discrepancy to +1 ± 6 msec and improved correlation (r = 0.988).

Conclusion: LA electrograms can be used to estimate right atrial entrainment response, if antidromic activation of the LA is recognized and taken into account.
Catheter Ablation of Atrial Flutter Guided by Electroanatomic Mapping (CARTO): A Randomized Comparison to the Conventional Approach
Authors: WILLEMS STEPHAN , WEISS CHRISTIAN , VENTURA RODOLFO , RÜPPEL RUDOLF , RISIUS TIM , HOFFMANN MATTHIAS , MEINERTZ THOMAS
Published: August 2003

Electroanatomic vs Conventional Mapping for Atrial Flutter Ablation. Introduction: Three‐dimensional electroanatomic (CARTO) activation mapping of the cavotricuspid isthmus can be helpful to guide atrial flutter ablation, but to date has not heen investigated in comparison to conventional strategies. The aim of the present study was to assess the efficacy of the CARTO navigation system, especially with respect to the fluoroscopy time required for successful atrial flutter ablation.

Methods and Results: Eighty patients with recurrent common‐type atrial flutter were randomly assigned to temperature‐controlled radiofrequency (RF) catheter ablation, either guided by conventional criteria (group 1) or additionally oriented on electroanatomic mapping (group 2). In all patients, similar multipolar catheters were inserted into the coronary sinus and placed at the tricuspid annulus. respectively. In group 2, positioning of the mapping electrode and delivery of RF pulses within the cavotricuspid isthmus was mainly oriented on the CARTO map to achieve the most linear and continuous RF lesions. Abolition of intra‐atrial conduction verified by conventional criteria (group 1) and electroanatomic mapping (group 2) could be verified in all patients. The overall number of RF pulses (group 1: 16.7 ± 6.5; group 2: 13.2 ± 5.3) and mean procedure duration (group 1: 172.5 ± 47.4 min; group 2: 169.3 ± 47.3 min) were not different between the two groups, but mean fluoroscopy time was significantly shorter when the CARTO tecbnology was used (group 1: 29.2 ± 9.4 min; group 2: 7.7 ± 2.8 min; F = 0.0001). Recurrence of atrial flutter was observed in 3 (9%) patients in each group after a mean follow‐up of 8.5 ± 2.months.

Conclusion: Atrial flutter can be abolished effectively using the conventional technique as well as oriented on electroanatomic mapping. However, overall X‐ray exposure can he significantly reduced by the CARTO‐guided approach without prolongation of procedure duration.
Effect of Verapamil on Immediate Recurrence of Atrial Fibrillation
Authors: DAOUD EMILE G. , HUMMEL JOHN D. , AUGOSTINI RALPH , WILLIAMS STACY , KALBFLEISCH STEVEN J.
Published: August 2003

Immediate Recurrence of AF. Introduction: The purpose of this study was to assess the effect of verapamil on immediate recurrences of atrial fibrillation occurring after successful electrical cardioversion.

Methods and Results: The effect of verapamil on the recurrence of atrial fibrillation within 5 minutes after successful transthoracic cardioversion was assessed in 19 (5%) of 364 patients undergoing electrical cardioversion. The mean duration of atrial fibrillation was 4.44 ± 3.0 months. In the 19 patients, cardioversion was successful after each of three consecutive cardioversion attempts per patient; however, atrial fibrillation recurred 0.4 ± 0.3 minutes after cardioversion. Verapamil 10 mg was administered intravenously and fourth cardioversion was performed. Cardioversion after verapamil was successful in each patient, and atrial fibrillation did not recur in 9 (47%) of 19 patients (P < 0.001 vs before verapamil). In the remaining 10 patients in whom atrial fibrillation recurred, the duration of sinus rhythm was significantly longer compared with before verapamil (3,6 ± 2.4 min, P < 0.001). The density of atrial ectopy occurring after cardioversion was significantly less after verapamil (21 ± 14 ectopic beats per min) compared with before verapamil (123 ± 52 ectopic beats per min, P < 0.001).

Conclusion: Among patients with immediate recurrence of atrial fibrillation after electrical cardioversion, acute calcium channel blockade by verapamil reduces recurrence of atrial fibrillation and extends the duration of sinus rhythm.
Electrophysiologic Endocardial Mapping from a Noncontact Nonexpandable Catheter: A Validation Study of a Geometry‐Based Concept
Authors: JIA PING , PUNSKE BONNIE , TACCARDI BRUNO , RUDY YORAM
Published: August 2003

Electrophysiologic Noncontact Endocardial Mapping. Introduction: The need for high‐resulution simultaneous mapping of cardiac excitation and arrhythmias on a heat‐hy‐heat basis is widely recognized. Here we validate a noncontact mapping approach that combines a spiral catheter design with mathematical reconstruction to generate potential maps, electrograms, and activation maps (isochrones) on the entire left ventricular endocardial surface during a single beat. The approach is applicable to any heart chamher.

Methods and Results: The catheter is 3 mm (9 French) in diameter and carries 96 electrodes. Reconstruction accuracy is evaluated through direct comparison with endocardial data measured with 95 needle electrodes. Results show that endocardial potentials, electrograms, and isochrones are reconstructed with good accuracy during pacing from single or multiple sites (simulating ectopic activity). Pacing sites can be located to within 5 mm of their actual position, and intersite distances of 17 mm can be resolved during dual pacing. The reconstructed potential pattern reflects the intramural depth of pacing. The reconstructions are robust in the presence of geometric errors, and the accuracy is minimally reduced when only 62 catheter electrodes are used (32 are sufficient for pacing site localization).

Conclusion: The study demonstrates that simultaneous endocardial mapping can be accomplished during a single beat from a spiral‐shaped noncontact catheter with good accuracy.
Early Down‐Regulation of K+ Channel Genes and Currents in the Postinfarction Heart
Authors: HUANG BOYU , QIN DAYl , EL‐SHERIF NABIL
Published: August 2003

Down‐Regulation oi K+ Channel Genes and Currents. Introduction: Down‐regulaticn of key K+ channel subunit gene expression and K+ currents is a universal response to cardiac hypertrophy, whatever the cause, including the postmyocdardial infarction (post‐Ml) remodeled heart.

Methods and Results: We investigated the hypothesis that down‐regulation of K+ channel genes and currents post‐MI occurs early and before significant remodeled hypertrophy of the noninfarcted myocardium could be detected. We investigated (1) the incidence of induced ventricular tachyar‐rhythmias (VT) in 3‐day post‐MI rat heart; (2) action potential (AP) characteristics of isolated left ventricular (LV) myocytes from sham‐operated and 3‐day post‐MI heart; (3) time course of changes in outward K+ currents Ito‐fast(f) Ikin isolated myocytes from 3‐day and 4‐week post‐MI noninfarcted LV and compared the changes with sham‐operated animals; and (4) changes in the messenger and protein levels of Kv2.1, Kv4.2. and Kv4.3 in the LV and right ventricle of 3‐day post‐MI heart. Sustained VT was induced in 6 of 10 3‐day post‐MI rats and in none of 8 sham rats. The membrane capacitance of myocytes isolated from 3‐day post‐MI noninfarcted LV was not significantly different from control, whereas membrane capacitance 4‐week post‐MI was significantly higher, reflecting the development of hypertrophy. AP duration was increased and the density of Ito‐f and Ik were significantly decreased in 3‐day post‐MI LV myocytes compared with sham. The reduced density of Ito, did not significantly differ in 4‐week post‐MI LV myocytes, whereas the density of Ik was decreased further at 4 weeks post‐MI. The changes in Ito‐f and Ik correlated with decreased messenger and protein levels of Kv4.2/Kv4.3 and Kv2.l, respectively.

Conclusion: These results support the hypothesis that down‐regulation of K+ channel gene expression and current in the post‐MI LV occurs early and may be dissociated from the slower time course of post‐MI remodeled hypertrophy. These changes may contribute to early arrhythmogenesis of the post‐MI heart.
Atrial Fibrillation in the Goat Induces Changes in Monophasic Action Potential and mRNA Expression of Ion Channels Involved in Repolarization
Authors: VAN DER VELDEN HUUB M.W. , VAN DER ZEE LUCIE , WIJFFELS MAURITS C.E.F. , VAN LEUVEN CARLO , DORLAND RICK , VOS MARC A. , JONGSMA HABO J. , ALLESSIE MAURITS A.
Published: August 2003

MAP Changes and Ion Channel Expression in Goat AF. Introduction: Sustained atrial fibrillation (AF) is characterized by a marked shortening of the atrial effective refractory period (AKRP) and a decrease or reversal of its physiolonic adaptation to heart rate. The aim of the present study was to investigate whether the AF‐induced changes in AKKP in the goat are associated with changes in the atrial monophasic action potential (MAP) and whether an abnormal expression of specific ion channels underlies such changes.

Methods and Results: Following thoracotomy, MAPs were recorded from the free wall of the right atrium hoth before induction of AF (control) and after cardioversion of sustained AF (>2 months) in chronically instrumented goats. In control goats. MAP duration at 80% repolarization (MAPD80) shortened (P < 0.01) from 132 ± 4 msec during slow pacing (400‐msec interval) to 86 ± 10 msec during fast pacing (180 msec). After cardioversion of sustained AF, the MAPD80, during slow pacing was as short as 67 ± 5 msec (electrical remodeling). Increasing the pacing rate resulted in prolongation (P = 0.02) of the MAPD80 to 91 ± 6 msec. Also. MAPD20 (20% repolarization) shortened (P = 0.05) from 32 ± 4 msec (400 msec) to 14 ± 7 msec (180 msec) in the control goats, whereas it prolonged (P = 0.03) from 20 ± 3 msec (400 msec) to 33 ± 5 msec (180 msec) in sustained AF, mRNA expression of the L‐type Ca2+ channel α1c gene and Kv1.5 potassium channel gene, which underlie Ica, and Ikur respectively, was reduced in sustained.AF compared with sinus rhythm hy 32% (P = 0.01) and 45% (P < 0.01). respectively. No significant changes were found in the mRNA levels of the rapid Na+ channel, the Na+/Ca2+ exchanger, or the Kv4.2/4.3 channels responsible for I10.

Conclusion: AF‐induced electrical remodeling in the goat comprises shortening of MAPD and reversal of its physiologic rate adaptation. Changes in the time course of reploarization of the action potential are associated with changes in mRNA expression of the α subunit genes of the L.‐type Ca2+ channel and the Kvl.5 potassium channel.
Connexin40‐Deficient Mice Exhibit Atrioventricular Nodal and Infra‐Hisian Conduction Abnormalities
Authors: VANDERBRINK BRIAN A. , SELLITTO CATERINA , SABA SAMIR , LINK MARK S. , ZHU WEI , HOMOUD MUNTHER K. , ESTES N.A. MARK , PAUL DAVID L. , WANG PAUL J.
Published: August 2003

AV Nodal and Infra‐Hisian Conduction in Cx40 Mice. Introduction: Previous electrophysiologic investigations have described AV conduction disturbances in connexin4(Cx40)‐deficient mice. Because expression or(Cx40 occurs predominantly in the atria and His‐Purkinje system of the mouse heart, the AV conduction disturbances were thought to be secondary to disruption in His‐Pnrkinje function. However, the lack of a His‐bundle electrogram recording in the mouse has limited further investigation of the importance of Cx40. Using a novel technique to record His‐bundle recordings in Cx40‐deficient mice, we define the physiologic importance of defciencies in Cx40.

Methods and Results: Ten Cx40‐/‐ mice and 11 Cx40+/+ controls underwent a blinded, in vivo, closed chest electrophysiology study at 9 to 12 weeks of age. In the Cx40+/+ mice, the PR interval was significantly longer compared with Cx40+/+ mice (44.6 ± 6.4 msec vs 36.0 ± 4.1 msec, P = 0.002). Not only the HV interval (14.0 ± 3.0 msec vs 10.4 ± 1.2 msec, P = 0.003) but also the AH interval (33.2 ± 4.8 msec vs 27.1 ± 3.7 msec, P = 0.006), AV Wenckebach cycle lengths, and AV nodal effective and functional refractory periods were prolonged in Cx40‐/‐ compared with Cx40+/+ mice.

Conclusion: Cx40‐deficient mice exhibit significant delay not only in infra‐Hisian conduction, as would be expected from the expression of Cx40 in the His‐Purkinje system but also in the electrophysiologic parameters that reflect AV nodal conduction. Our data suggest a significant role of Cx40 in atrionodal conduction and/or in proximal His‐bundle conduction,
Infant Case with a Malignant Form of Brugada Syndrome
Authors: SUZUKI HIROSHI , TORIGOE KATSUMI , NUMATA OSAMU , YAZAKI SATOSHI
Published: August 2003

Infant with Brugada Syndrome.We report a 6‐nionth‐old Japanese infant with a malignant form of Brugada syndrome, who had frequent episodes of ventricular fibriitation (VF) and nonsustained polymorphic ventricular tachycardia (VT). To the best of our knowledge, this infant is the youngest patient reported to have Brugada syndrome. Continuous infusion of a β‐adrenergic agonist and intravenous injection of a parasympathetic antagonist suppressed the electrical storm of polymorphic VT and VF. Combined oral administration of a β1‐adrenergic agonist, a parasympathetic antagonist, and quinidine has successfully suppressed recurrences of VT or VF for 6 months, and the combination may have the potential to decrease the incidence of VT or VF as an adjunctive therapy with prophylactic placement of an implantable cardioverter defibrillator.
Atrioventricular Nodal Reentrant Tachycardia Requiring Ablation on the Mitral Annulus
Authors: ALTEMOSE GREGORY T. , SCOTT LUIS R. , MILLER JOHN M.
Published: August 2003

Mitral Ablation for AV Nodal Reentry. We report a case of initial transient success during ablation for typical AV nodal reentrant tachycardia utilizing traditional right‐sided approaches, followed by recurrence of the same tachycardia and an ultimately successful ablation on the posteromedial mitral annulus.
Intradevice Interaction in a Dual Chamber Implantable Cardioverter Defibrillator Preventing Ventricular Tachyarrhythmia Detection
Authors: SHIVKUMAR KALYANAM , FELICIANO ZENAIDA , BOYLE NOEL G. , WIENER ISAAC
Published: August 2003

Intradevice Interaction in Dual Chamber ICD. Failure to detect ventricular tachycardia and/or ventricular fibrillation by implantable cardioverter defibrillators (ICDs) is a rare but serious problem. We report a case of failure to detect an episode of indueed ventricular tachycardia by a dual cbamber ICD, due to abbreviation of ventricular detection window secondary to programmed pacing parameters and a rate‐smoothing algorithm. In this patient, the intradevice interaction was corrected by programming rate‐smoothing off. This report highlights the potentially lethal consequences of critical timing relationships among the pacing function, arrhythmia detection, and the characteristics of the arrhythmia when using a modern dual chamber ICD. Physicians responsible for patients with ICDs must be aware of such interactions.
Localization of Arrhythmogenic Triggers of Atrial Fibrillation
Authors: ASHAR MANISHA S. , PENNINGTON JOSEPH , CALLANS DAVID J. , MARCHLINSKI FRANCIS E.
Published: August 2003

Arrhythmogenic Triggers of Atrial Fibrillation. Introduction: Mapping procedures to identify triggers of atrial fibrillation from pulmonary veins (PVs) are not well established. We sought to determine the value of multipolar recordings from the coronary sinus (CS) and crista terminalis (CT) for identifying the origin of paced and atrial premature depolarizations (APDs) initiating atrial fibrillation from left versus right PVs.

Methods and Results: Fifteen patients with paroxysmal atrial fibrillation refractory to medications had decapolar catheters (5‐mm electrode, 2‐nmi interelectrode spacing) placed in the CS and posterior medial to the CT. Bipolar electrograms were recorded at each site. Electroanatomic left atrial endocardial maps were created in sinus rhythm, and each PV was identified and paced. During spontaneous APDs initiating atrial fibrillation and PV pace maps, the atrial activation and the earliest electrogram at CS and CT were compared. PV sites were designated as sites of origin of APDs when (1) intracardiac electrograms in the CS and CT during arrhythmogenic APDs matched those of Pv pace maps, (2) local activation preceded CS and CT recordings by at least 40 msec (all sites), and (3) atrial depolarizations were eliminated by application of radiofrequency energy (24/26 sites). Pacing from each of the 30 right PV sites resulted in proximal to distal CS activation and later recordings at the CS than the CT (earliest CS‐CT activation range: ‐15 to ‐ 58 msec, mean ‐32 ± 12). In contrast, pacing from the left PV sites typically (28/30 sites) activated the CS from the distal to proximal poles and demonstrated simultaneous or earlier (CS‐CT range: ‐14 to +54 msec, mean 13 ± 17) recordings of the CS than the CT (P < 0.0001). For 13 APDs mapped to the right PVs, CS minus CT activation was ‐17 to ‐49 msec (mean ‐ 31 ± 8). For 13 APDs localized to the left PVs, the CS minus CT activation time ranged from ‐8 to +28 msec (mean 14 ± 15).

Conclusion: Activation sequence mapping from multipolar catheters placed in the CS and along the posterior medial CT rapidly differentiates right and left PV sites of origin of atrial depolarization.
Importance of the Atrial Channel for Ventricular Arrhythmia Therapy in the Dual Chamber Implantable Cardioverter Defibrillator
Authors: DIJKMAN BARBARA , WELLENS HEIN J.J.
Published: August 2003

Atrial Channel and VT Therapy in ICD. Introduction: Performance of dual chamber implantable cardioverter defibrillator (ICD) systems bas been judged based on functioning of the ventricular tachycardia:supraventricular tachycardia (VT:SVT) discrimination criteria and DDD pacing. The purpose of this study was to evaluate the use of dual chamber diagnostics to improve the electrical and antiarrhythmic therapy of ventricular arrhythmias.

Methods and Results: Information about atrial and ventricular rhythm in relation to ventricular arrhythmia occurrence and therapy was evaluated in 724 spontaneous arrhythmia episodes detected and treated by three types of dual chamber K Ds in 41 patients with structural heart disease. Device programming was based on clinically documented and induced ventricular arrhythmias. In ambulatory patients, sinus tachycardia preceded ventricular arrhythmias more often than in the hospital during exercise testing. The incidence of these VTs could be reduced by increasing the dose of a beta‐blocking agent in only two patients. In five patients in whom sinus tachycardia developed after onset of hemodynamic stable VT, propranolol was more effective than Class III antiarrhythmics combined with another beta‐blocking agent with regard to the incidence of VT and pace termination. In all but three cases, atrial arrhythmias were present for a longer time before the onset of ventricular arrhythmias. During atrial arrhythmias, fast ventricular rates before the onset of ventricular rate were observed more often than RR irregularities and short‐long RR sequences. Dual chamber diagnostics allowed proper interpretation of detection and therapy outcome in patients with different types of ventricular arrhythmia.

Conclusion: The advantages of the dual chamber ICD system go further than avoiding the shortcomings of the single chamber system. Information from the atrial chamber allows better device programming and individualization of drug therapy for ventricular arrhythmia.
Effect of Sodium Channel Blockers on ST Segment, QRS Duration, and Corrected QT Interval in Patients with Brugada Syndrome
Authors: SHIMIZU WATARU , ANTZELEVITCH CHARLES , SUYAMA KAZUHIRO , KURITA TAKASHI , TAGUCHI ATSUSHI , AIHARA NAOHIKO , TAKAKI HIROSHI , SUNAGAWA KENJI , KAMAKURA SHIRO
Published: August 2003

ST Elevation in Brugada Syndrome. Introduction: Brugada syndrome is characterized by an ST segment elevation in leads V1‐V3 and a high incidence of ventricular fibrillation (VF). A mutation in a cardiac Na+ channel gene, SCN5A, has been linked to Brugada syndrome, and sodium channel blockers have been shown to be effective in unmasking the syndrome when concealed. The aim of this study was to examine the effects of Na+ channel blockers on ST segment elevation, QRS, corrected QT (QTc) interval, and ventricular arrhythmias in patients with Brugada syndrome.

Methods and Results: We examined the effects of three different Na+ channel blockers (flecainide, disopyramide, and mexiletine) on the amplitude of the ST segment 20 msec after the end of QRS (ST20), QRS duration, QTc interval measured from 12‐lead ECG, and ventricular arrhythmias in 12 Brugada and 10 control patients. Maximum ST20 observed in the V2 or V3 leads under baseline conditions was greater in the Brugada patients than in control patients, whereas QRS duration and maximum QTc interval were no different between the two groups. Flecainide and disopyramide, but not mexiletine, significantly increased maximum ST20 and QRS duration in both groups, although these effects were much more pronounced in the Brugada patients. The increases in ST20 and QRS duration with flecainide were significantly larger than those with disopyramide. An increase of 0.15 mV in ST20 with flecainide separated the two groups without overlap. Ventricular premature complexes developed only with flecainide in Brugada patients (3/12) displaying a marked ST elevation but not widening of QRS.

Conclusion: Our findings suggest that Na+ channel blockers amplify existing INa and possibly other ion channel defects, with a potency inversely proportional to the rate of dissociation of the drug from the Na+ channel, thus causing a prominent elevation of the ST segment and, in some cases, prolongation of QRS duration in patients with Brugada syndrome.
Continuous Telemetry from a Chronic Canine Model of Sudden Cardiac Death
Authors: KILLINGSWORTH CHERYL R. , RITSCHER DAVID E. , WALCOTT GREGORY P. , ROLLINS DENNIS L. , IDEKER RAYMOND E. , SMITH WILLIAM M.
Published: August 2003

Continuous Telemetry in a Dog Model of Sudden Death. Introduction: We sought to develop a continuously telemetered animal model of sudden cardiac death (SCD) to study the role of existing infarcts and acute ischemia in fatal arrhythmias.

Methods and Results: A telemetry system capable of recording eight channels of electrophysiologic data continuously and chronically has been developed. To demonstrate the use of this technology in an animal model of sudden death. 12 anesthetized dogs were instrumented with eight electrodes located in endocardium of the right side of the heart, epicardium of the left ventricle (LV), or in the subcutaneous tissues. The left anterior descending (LAD) coronary artery was occluded for 90 minutes and reperfused to produce LV infarction. A copper wire was placed in the left circumflex (LCX) coronary artery to cause intimal injury in a second arterial bed. The telemetry unit recorded deaths in seven animals between 19 to 64 hours after surgery. Five animals that did not experience SCD by the fifth postoperative day served as controls. There were three modes of SCD: complex ventricular ectopy that degenerated into ventricular fibrillation VF (n = 4); normal sinus rhythm that suddenly degenerated into VF (n = 1); and bradycardia (RK intervals > 1.000 msec) that lasted >3 minutes and preceded VF (n = 2). ST segment changes were significantly greater in the LCX‐bed electrograms for tachyarrhythmic compared to bradyarrhythmic deaths (mean ± SD; 4.0 ± 3.4 mV and 0.2 ± 0.8 mV, respectively). Fast Fourier transform showed the peak frequency of VF 10 seconds after onset was significantly higher in the five dogs with initial tachyarrhythmic compared with the VF that followed profound bradycardia (6.5 ± 3.1 Hz and 3.7 ± 0.6 Hz. respectively). Computer‐assisted planimetry of postmortem heart slices revealed that infarcts in the two dogs with bradycardie events were larger (19.7%± 2.2% of the LV and septal mass) than in the five dogs with tachyarrhythmias (7.7%± 2.4%) or in the five control dogs (11.9%± 8.1%).

Conclusion: It is possible to record via telemetry the events leading to SCD in an animal model. Continuous telemetry monitoring demoastrated that both tachyarrhythmias and bradyarrhythmias ultimately resulted in VF in an animal model of SCD. Animals with tachyarrhythmic deaths had greater ischemia in the LCX bed, smaller preexisting infarcts, and higher VF peak frequency than animals with bradyarrhythmic deaths.
Colocalization of Tenascin and Sympathetic Nerves in a Canine Model of Nerve Sprouting and Sudden Cardiac Death
Authors: LAI ANGELA C. , WALLNER KURT , CAO JI‐MIN , CHEN LAN S. , KARAGUEUZIAN HRAYR S. , EISHBEIN MICHAEL C. , CHEN PENG‐SHENG , SHARIFI BEHROOZ G.
Published: August 2003

Tenascin and Cardiac Nerve Sprouting. Introduction: Sympathetic nerve sprouting after myocardial infarction (MI) may contribute significantly to the occurrence of ventricular arrhythmia and sudden cardiac death. Tenascin‐X (TnX), a matrix protein known to be associated with nerve growth in central and peripheral nerves, also may play a role in cardiac nerve sprouting after MI.

Methods and Results: Immunocytochemical staining techniques were used to identify nerves in 5‐μm serial sections from 6 normal dogs and 11 dogs with MI. Among the dogs with MI, 4 also received nerve growth factor infusion to the left stellate ganglion. The time between MI to tissue harvest averaged 35.7 ± 14.4 days. Tyrosine hydroxylase (TH) stain was used to identify sympathetic nerves, and growth‐associated protein‐43 (GAP‐43) was used to identify growing nerves. Polyclonal antibody was obtained for use in identifying TnX. Nerves were evident in both the infarcted and noninfarcted areas. Many nerves were found around blood vessels. A total of 181 nerves in 69 slides were examined: 89 were from noninfarcted myocardium, 4 from infarct, 13 from infarct horder zone, and 75 from perivascular regions. Except in normal dogs, all nerves stained positive for TH also stained positive for GAP‐43, indicating sympathetic nerve sprouting after MI. In all dogs, the nerves that stained positive for TH also stained positive for TnX.

Conclusion: There is a colocalization of TnX, GAP‐43, and TH in sprouted cardiac nerves. These results suggest that TnX is important not only in the existing normal myocardial nerve cells but also in cardiac sympathetic nerve sprouting after MI.
Is all Ventricular Fibrillation the Same?
Authors: TANEJA TARESH , GOLDBERGER JEFFREY , JOHNSON DAVID , KADISH ALAN
Published: August 2003

Characteristics of Induced VF. Introduction: Little information is available on the relationship between the mode of induction of ventricular fibrillation (VF) to VF characteristics.

Methods and Results: VF was induced from the anterior left ventricle by programmed electrical stimulation, burst pacing, alternating current (AC), high current 82 at a site remote from SI, T wave shock, and intersecting wavefronts in seven normal dogs and seven dogs with chronic myocardial infarction. Using two electrode arrays, 112 electrograms were recorded from the anterior and lateral wall. Cycle lengths were analyzed and activation vectors were created by summing orthogonally recorded bipolar electrograms. The magnitude of the vector loops was integrated over time to produce an “ensemble vector” index (EVI) whose magnitude is high when beat‐to‐beat activation direction is consistent and low when activation direction is variable. T wave shock‐induced W had a significantly longer cycle length 1 to 5 seconds after VF onset than other modes of induction (P < 0.05). The frequency‐corrected EVI was significantly larger for AC current and T wave shock‐induced VF as opposed to all other modes of VF induction in early VF (P < 0.0001). After 10 seconds of VF, these differences persisted only on the anterior wall.

Conclusion: VF induced in animals by T wave shock and AC current had different characteristics than VF induced by other methods. These findings may have implications for our understanding of VF pathophysiology.
Fibrillation is More Complex in the Left Ventricle than in the Right Ventricle
Authors: ROGERS JACK M. , HUANG JIAN , PEDOTO RAMON W. , WALKER ROBERT G. , SMITH WILLIAM M. , IDEKER RAYMOND E.
Published: August 2003

VF Patterns in the Right and Left Ventricles.Introduction:The mechanisms that maintain ventricular fibrillation (VF) are not completely understood. It has been proposed that increased ventricular wall thickness destabilizes VF wavefronts and therefore is an important determinant of VF activation patterns. We hypothesized that if this is the case, then VF patterns on the thin‐walled right ventricle (RV) should he simpler than those on the thick‐walled left ventricle (LV).

Methods and Results: In seven open chest pigs, we mapped VF simultaneously from two epicardial recording arrays, one on the RV and one on the LV. Each array contained 504 unipolar electrodes (in a 21 × 24 grid) spaced by 2 mm. We used specialized pattern analysis methods to compute quantitative descriptors of RV and LV activation patterns. Our data show that VF is more organized in the RV than the LV, containing fewer, larger wavefronts that follow fewer distinct pathways and are less likely to fragment or collide with other wavefronts. The incidence, size, and cycle length of reentrant circuits were similar in the two ventricles, but RV reentry persisted for more cycles. These results are not predicted by the differences in electrophysiologic properties between LV and RV that have been reported in mammalian hearts.

Conclusion:The geometry of the ventricular wall, particularly wall thickness, is an important determinant of VF activation patterns.
Profibrillatory Effects of Verapamil but Not of Digoxin in the Goat Model of Atrial Fibrillation
Authors: DUYTSCHAEVER MATTIAS F. , GARRATT CLIFFORD J. , ALLESSIE MAURITS A.
Published: August 2003

Profibrillatory Effects of Verapamil. Introduction: Verapamil and digoxin have been shown to modulate tachycardia‐induced atrial electrical remodeling. The goal of the present study was to determine the direct effects of verapamil and digoxin on atrial fibrillation (AF), before and after electrical remodeling.

Methods and Results: In six goats we measured the AF cycle length (AFCL) and duration of AF (DurAF) of 50 consecutive induced paroxysms, before (t = 0) and after 24 hours (t = 24) of electrical remodeling. During AF, conduction velocity (CVAF), refractory period (RPAF), and type of AF (I, II, III) were determined. Verapamil was administered at a loading dose of 0.1 mg/kg, followed by a continuous (2‐hour) infusion of 5 μ/kg/min. Digoxin was given intravenously as a single 0–02 mg/kg bolus. At t = 0 and t = 24, digoxin and verapamil caused a significant slowing of the ventricular rate of >40%. Digoxin bad no effect on DurAF, AFCL, CVAF, or RPAF. Infusion of verapamil had a direct proarrhythmic effect. Both at t = 0 and t = 24, AFCL and RPAF were shortened by about second 15%. During acute AF, verapamil prolonged the average duration of AF paroxysms from 7 to 16 seconds. After 24 hours of AF, the proarrhythmic effect was much stronger. Shortly after starting infusion (6 ± 2 min), verapamil converted paroxysmal AF into sustained AF. As long as verapamil infusion was maintained, AF no longer terminated in any of the goats. This effect was associated with an increase in AF fragmentation from type I to type II‐III.

Conclusion: Verapamil shortens AFCL and RPAF in the presence and absence of electrical remodeling. After 24 hours, it exerted a marked proarrhythmic effect and converted paroxysmal (type I) into sustained (type III) AF. In contrast, digoxin had no effect on the rate or stability of AF.
Termination of Spiral Waves with Biphasic Shocks:
Authors: ANDERSON CORY , TRAYANOVA NATALIA , SKOUIBINE KJRILL
Published: August 2003

Virtual Electrodes in Biphasic Defibrillation. Introduction: This simulation study seeks to extend the virtual electrode polarization (VKP) theory for defibrillation to explain the success and failure of biphasic shocks. The goals of the study are to (1) provide insight into why optimal biphasic shocks have a lower voltage defibrillation threshold than monophasic shocks, (2) examine the mechanisms of biphasic shock failure and to determine whether they differ from those of monophasic and (3) study how the timing of biphasic shock delivery to a spiral wave affect voltage defibrillation threshold.

Methods and Results: A spiral wave is initiated in a bidomain representation of a 2‐cm × 2‐cm sheet of ventricular myocardium. The model incorporates nonuniform fiber curvature, membrane kinetics suitable for high‐strength shocks, and electroporation. A spatially uniform extracellular field is delivered by line electrodes. The shock establishes VEP that dictates the postshock activity in the tissue. Our results demonstrate that the second phase of biphasic shocks leaves the tissue with substantially smaller postshock excitable gap, thus eliminating the majority of the substrate for reinitiation of reentrant activity. Further, the occurrence of break excitations for weaker biphasic shocks indicates that the mechanisms for biphasic shock failure are more complex than for monophasic shocks. Biphasic voltage defibrillation thresholds range from S to 16 V/cm, depending on the position of the spiral wave. An increase in the amount of preshock excitable gap leads to an increase in voltage defibrillation threshold.

Conclusion: I his study demonstrates the importance of VKP and its interaction with preshock activity in the success and failure of biphasic defibrillation shocks.
Time Course of Left Atrial Mechanical Recovery After Linear Lesions:
Authors: AVITALL BOAZ , URBONAS ARVYDAS , URBONIENE DALIA , MILLARD SCOTT , HELMS RAY
Published: August 2003

LA Mechanical Function After Linear Lesions. Introduction: The extent of left atrial (LA) mechanical function recovery after creation of linear lesions using the loop catheter has not been determined.

Methods and Results: LA mechanical function was assessed before and after linear lesions using transthoracic two‐dimensional and Doppler echocardiography in two groups: (I) normal, which consisted of eight healthy dogs in normal sinus rhythm (NSR); and (2) atrial fibrillation (AF), which consisted of nine dogs in spontaneous AF for 6 months following rapid pacing‐induced AF. NSR was restored with linear lesions in all AF dogs. All animals were in NSR 5 months after linear lesions. In the normal dogs, the maximal velocity of the transmitral flow “A” wave was reduced by 42% during the first week postablation and by 24% at 5 months versus preablation. At 5 months, no differences in LA function were noted between the normal and the AF group for all measured Doppler parameters. At 5 months, the LA systolic area in AF dogs was reduced by 40% (preablation 12.9 ± 2.9 cm2, postablation 7.6 ± 1.2 cm2; P < 0.01) and in the normal dogs by 21% (preablation 10.0 ± 0.9 cm2, postablation 7.8 ± 1.2 cm2; P < 0.02), being the same in both groups within 3 months of recovery.

Conclusion: The creation of linear lesions with the loop catheter does not result in LA expansion. In normal dogs, LA mechanical activity is reduced for 3 weeks postablation. The time course of LA mechanical function recovery is the same for the AF and the NSR dogs, and it is complete at 3 months postablation. At 5 months, LA systolic function parameters in both groups are reduced by 24% versus the preablation values of the normal dogs. Linear lesions result in a significant reduction in LA size.
Endocardial Noncontact Activation Mapping of Idiopathic Left Ventricular Tachycardia
Authors: SRA JASBIR , BHATIA ATUL , KRUM DAVID , AKHTAR MASOOD
Published: August 2003

Mapping of Idiopathic Ventricular Tachycardia. Idiopathic left ventricular tachycardia with a right bundle, left‐axis deviation is thought to originate from posterior fascicles. Recently, there has been considerable interest in the anatomic and mechanistic basis of this arrhythmia. We report our experience with a 26‐year‐old man in whom new noncontact mapping technology was used to acquire detailed data from the left ventricle, identify the mid‐diastolic potential and part of the ventricular tachycardia circuit, and perform successful ablation. This information helped define the physiologic aspects of this unique tachycardia.
Long QT Syndrome:
Authors: JANUARY CRAIG T. , GONG QIUMING , ZHOU ZHENGFENG
Published: August 2003

HERG Channel Dysfunction in LQT2. LQT2 is one form of the congenital long QT syndrome, It results from mutations in the human ether‐a‐go‐go‐related gene (HERG), and more than 80 mutations, usually causing single amino acid substitutions in the HERG protein, are known, HFRG encodes the ion channel pore‐forming subunit protein for the rapidly activating delayed rectifier K+ channel (IKr) in the heart. This review summarizes current findings about mutations causing LQT2, the mechanisms by which mutations may cause the clinical phenotype of a reduction in IKr and a prolonged QT interval, and how this may be involved in the generation of ventricular arrhythmias.
Relatively Benign Clinical Course in Asymptomatic Patients with Brugada‐Type Electrocardiogram Without Family History of Sudden Death
Authors: TAKENAKA SHIHO , KUSANO KENGO FUKUSHIMA , HISAMATSU KENICHI , NAGASE SATOSHI , NAKAMURA KAZUFUMI , MORITA HIROSHI , MATSUBARA HIROMI , EMORI TETSURO , OHE TOHRU
Published: August 2003

Asymptomatic Brugada‐Type ECG.
Introduction: The incidence of sudden death or ventricular fibrillation (VF) in asymptomatic Brugada syndrome patients with a family history of sudden death is reported to be very high. However, there are few reports on the prognosis of asymptomatic Brugada syndrome patients without a family history of sudden death.

Methods and Results: Eleven patients (all male; mean age 40.5 ± 9.6 years, range 26 to 56) with asymptomatic Brugada‐type ECG who had no family history of sudden death were evaluated. The degrees of ST segment elevation and conduction delay on signal‐averaged ECG (SAECG) before and after pilsicainide were evaluated in all 11 patients. VF inducibility by ventricular electrical stimulation also was evaluated in 8 of 11 patients. Patients were followed for a period of 9 to 84 months (mean 42.5 ± 21.6). The J point level was increased (V1 :0.19 ± 0.09 mV to 0.36 ± 0.23 mV; V2: 0.31 ± 0.12 mV to 0.67 ± 0.35 mV) by pilsicainide. Conduction delay was increased (total QRS: 112.2 ± 6.3 msec to 131 7 ± 6.3 msec; under 40 μ V: 42.0 ± 8.5 msec to 52.7 ± 12.7 msec; last 40 msec: 17.4 ± 5.9 μ V to 10.4 ± 6.1 μ V) on SAECG by pilsicainide. VF was induced in only 1 of 8 patients. None of the patients had syncope or sudden death during a mean follow‐up of 42.5 ± 21.6 months.

Conclusion: This study suggests that asymptomatic patients with Brugada‐type ECG who have no family history of sudden death have a relatively benign clinical course.
Sympathetic Activation Enhances QT Prolongation by Quinidine
Authors: DARBAR DAWOOD , FROMM MARTIN F. , DELL'ORTO SIMONETTA , RODEN DAN M.
Published: August 2003

Salt Restriction and QT Prolongation.
Introduction: Salt restriction results in endogenous sympathetic activation, and we previously showed that plasma concentrations of quinidine measured after oral drug administration are increased during a low‐salt diet. However, it is not known whether, independent of effects on plasma concentration, the extent to which quinidine prolongs the QT interval also is modulated by changes in endogenous sympathetic activity.

Methods and Results: In these studies, we evaluated quinidine concentration‐QT relations during low‐salt (10 mEq/day for 8 days) and high‐salt (400 mEq/day for 8 days) diets, with or without beta blockade in normal volunteers. In the absence of beta blockade, the concentration producing a fixed (15%) increase in QTc was significantly lower with salt restriction: 1.2 ± 0.4 μg/mL (low salt) versus 2.2 ± 0.4 μg/mL (high salt) (P < 0.01). With beta blockade, this difference was abolished: 1.9 ± 0.3 μg/mL (low salt + beta blockade) versus 2.1 ± 0.3 μg/mL (high salt + beta blockade). QT morphologic abnormalities including bifid T waves and U waves were abolished with beta‐adrenergic blockade.

Conclusion: Sympathetic activation by a low‐salt diet not only modulates drug disposition but also increases sensitivity to drug‐induced QT prolongation.
Electroanatomic Characterization of Conduction Barriers in Sinus/Atrially Paced Rhythm and Association with Intra‐Atrial Reentrant Tachycardia Circuits Following Congenital Heart Disease Surgery
Authors: LOVE BARRY A. , COLLINS KATHRYN K. , WALSH EDWARD P. , TRIEDMAN JOHN K.
Published: August 2003

Conduction Barriers in Sinus Rhythm and IART.
Introduction: The electrophysiologic mechanism of intra‐atrial reentrant tachycardia (IART) is generally thought to be a macroreentrant circuit revolving around a nonconductive or highly anisotropic barrier. However, the electrical and anatomic substrate that supports these circuits has been incompletely defined. Our objectives were to characterize the atria of patients with IART using electroanatomic mapping in sinus or atrially paced rhythm and to determine whether electrical barriers identified in sinus/atrially paced rhythm are associated with IART circuits.

Methods and Results: Eighteen patients with IART and a remote history of repaired or palliated congenital heart disease were studied [8 biventricular repair, 8 single ventricle palliation (7 Fontan), and 2 Mustard repair]. Thirteen patients had a right AV valve. In sinus/atrially paced rhythm, electrical evidence of a crista terminalis was identified in 11 patients, an atriotomy in 12, and ≥ 1 right atrial free‐wall scar in 11. In 26 IART circuits characterized, 12 used the right AV valve as a central obstacle, 6 used a right atrial free‐wall scar, 3 used an atriotomy, 3 used the crista terminalis, and 2 circuits used an atrial septal scar. All central obstacles used by IART circuits were identified in sinus/atrially paced rhythm.

Conclusion: The crista terminalis, atriotomy, and right atrial scars can be identified in patients with repaired congenital heart disease by electroanatomic mapping in sinus/atrially paced rhythm. These conduction barriers frequently function as the central obstacle for IART. Demonstration of such features may help focus investigational mapping without reliance on spontaneous initiation of the tachycardia.
Reversal of Deteriorated Fractal Behavior of Heart Rate Variability by Beta‐Blocker Therapy in Patients with Advanced Congestive Heart Failure
Authors: LIN LIAN‐YU , LIN JIUNN‐LEE , DU CHAO‐CHENG , LAI LING‐PING , TSENG YUNG‐ZU , HUANG SHOEI K. STEPHEN
Published: August 2003

Beta‐Blocker Therapy and Heart Rate Variability.
Introduction: The slope of the power spectrum in heart rate variability (HRV) reflects the fractal or scaling behavior in HR dynamics and recently was confirmed as an independent predictor of postmyocardial infarction survival. Whether or not the new measurement in HRV foresees the functional evolution in patients with advanced congestive heart failure treated by β blockers is unclear.

Methods and Results: Sequential 24‐hour Holter ECG recordings were obtained at baseline, and 1 and 3 months after addition of atenolol therapy for advanced congestive heart failure in 10 patients. The slope and intercept of the regression line of power‐law behavior, the short‐ and intermediate‐term of detrended fluctuated analysis (DFA), the approximate entropy (ApEn), and the standard frequency spectra of the 24‐hour HRV were compared sequentially as well as with those in 12 age‐matched normal controls. The results showed that the slope (−1.70 ± 0.45 vs −1.22 ± 0.21; P < 0.05) and the intercept (5.11 ± 0.46 vs 5.62 ± 0.24; P < 0.05) of the regression line of power‐law behavior and the short‐term DFA (for 4 to 11 beats) (0.78 ± 0.18 vs 1.13 ± 0.21; P < 0.05) increased after 3 months of atenolol treatment. However, the change in intermediate‐term DFA (> 11 beats) and ApEn was not apparent (1.24 ± 0.21 vs 1.22 ± 0.15 and 1.34 ± 0.14 vs 1.36 ± 0.11; both P > 0.05). The evolution of the slope or intercept of the regression line of the HRV power spectrum did not correlate with the echocardiographic or clinical cardiac function, or with the frequency spectral components of the HRV (P > 0.05).

Conclusion: Additional beta‐blocker therapy upregulated the fractal behavior control of the HRV in patients with advanced congestive heart failure. The improvement was independent of subjective and objective global cardiac performance.