bluuebunny/crossref_metadata_2025 huggingface dataset:
The Architecture of the Atrial Musculature Between the Orifice of the Inferior Caval Vein and the Tricuspid Valve: The Anatomy of the Isthmus
Authors: CABRERA JOSE ANGEL , SANCHEZ‐QUINTANA DAMIAN , YEN HO SIEW , MEDINA ALEONSO , ANDERSON ROBERT H.
Published: April 2007

Anatomy of Electrophysiologic Isthmus. Introduction: Electrophysiologists recognize a so‐called “isthmus” in the right atrium through which passes the reentrant circuit of common atrial flutter. Ablative lesions placed in this narrow channel have proved effective in breaking the circuit. To the best of our knowledge, however, no study has been performed to establish the arrangement and orientation of the atrial myocardial fibers in this crucial area.

Methods and Results: We examined 28 normal heart specimens, identifying a quadrilateral area composed of three morphologic sectors between the inferior caval vein and the tricuspid valve confluent superiorly with the triangle of Koch. Within this quadrilateral, there are constant recesses, or sinuses, inferior and lateral to the orifice of the coronary sinus. The inferior isthmus measured an average of 31 ± 4 mm (range 19 to 40). Gross examination identified marked differences in the atrial wall forming the quadrilateral. A smooth anterior component forming the vestibule of the tricuspid valve was found in all the hearts, but variations in the remaining sectors were seen in ten specimens. The usually membranous posterior sector was noticeably muscular in three specimens, while the middle, trabecular sector was more membranous in five specimens. We demonstrated the orientation of the subendocardial atrial fibers by dissection in 14 specimens, revealing a relatively constant overall pattern in eight specimens and variations in fiber orientation in the remaining specimens.

Conclusion: There are considerable anatomic variations in the atrial wall that comprises the so‐called isthmus. The presence of recesses and membranous areas in some hearts and the variations in arrangement of the subendocardial fibers are relevant in improving understanding of conduction in this area.
Comparison of Standard and Irrigated Radiofrequency Ablation in the Canine Ventricle
Authors: SKRUMEDA LISA L. , MEHRA RAHUL
Published: April 2007

Standard and Irrigated RF Ablation Lesions. Introduction: radiofrequency ablation is successful for treating some arrhythmias but not for CAD‐VT, possibly due to insufficient lesion size. Irrigated electrodes were developed to apply higher power for longer duration to create larger lesions. Our objective was to characterize and compare irrigated and standard ablation in terms of lesion size, crater, and coagulum formation. Additionally, a method is proposed for creating large irrigated lesions without craters.

Methods and Results: Three ablation protocols were conducted in canine ventricles. Protocol I: standard ablation was performed in power mode at 10, 20, 30, and 50 W, and electrode‐temperature mode at 70° and 90°C (120 sec). Protocol II: irrigated ablation was conducted with 30 and 50 W (30 and 120 sec). Protocol III: to create large lesions without craters, irrigated ablation was performed at 20 W (5 and 10 min). With a standard electrode, the largest lesions were created using 20 W (358 ± 194 mm3) and using 90°C (301 ± 130 mm2). Ablation duration decreased with power for the power mode standard ablations. The largest irrigated lesions were formed using 50 W (986 ± 357 mm2). Large lesions without craters were created with irrigation using 20 W for 10 minutes (602 ± 175 mm2). Coagulum was seen for most standard ablations but infrequently for irrigated ablations. Craters were observed with 30 and 50 W irrigated ablation but were not observed with 20 W irrigated ablation.

Conclusion: Irrigated ablation created larger lesions than standard; large lesions may be created without craters using moderate power and long duration.
Tridimensional Mapping: Guided Modification of the Sinus Node
Authors: LEONELLI FABIO , RICHEY MARK , BEHEIRY SALWA , RAJKOVICH KATHLEEN , NATALE ANDREA
Published: April 2007

Tridimensional Mapping: Guided Modification of the Sinus Node. Radiofrequency (RF) catheter modification of the sinus node appears to he a promising therapeutic modality for the treatment of inappropriate sinus tachyeardia Modification, as opposed to total obliteration, of the atrial pacemaker requires precise localization of the sinus node. This has been successfully achieved with a multicatheter approach guided by intracardiac echocardiography. This article describes the first clinical use of a tridimensional nonfluoroscopic mapping system to guide successful RF modification of the sinus node in two cases of inappropriate sinus tachycardia. This system simplifies the current approach and greatly reduces the fluoroscopy time.
The Long QT Syndrome with Impaired Atrioventricular Conduction: A Malignant Variant in Infants
Authors: GORGELS ANTON P.M. , EADLEY FADEL AL , ZAMAN LIAQAT , KANTOCH MICHAL J. , HALEES ZOHAIR AL
Published: April 2007

Distal Conduction Disease in the Long QT Syndrome. Introduction: The long QT syndrome (LQTS) is occasionally complicated by impaired AV conduction, mostly 2:1 AV block. This form of LQTS can manifest before birth or during neonatal life, and it is more sporadic than familial. It is usually an isolated disorder, although it can be accompanied by a variety of cardiovascular and other anomalies. In spite of different treatment modes, mortality is high.

Methods and Results: The reported case presented not only with 2:1 AV conduction, but also with Wenckebach episodes with impaired right and left bundle branch conduction, and decremental conduction in the His‐Purkinje axis. We also observed sinus pauses and accelerated AV junctional escape beats.

Conclusion: Our findings, and similar observations by others., suggest involvement of the sinus node and the distal conduction system in this form of the LQTS. Several histologic studies have documented abnormalities within the conduction system, including apoptosis. Because of the rare occurrence and poor prognosis of the LQTS with impaired AV conduction, international guidelines for diagnosis and treatment are needed. Development of an internal cardiac defibrillator for this young age group is necessary.
The Architecture of the Sinus Node, the Atrioventricular Conduction Axis, and the Internodal Atrial Myocardium
Authors: ANDERSON ROBERT H. , HO SIEW YEN
Published: April 2007

Anatomy of Cardiac Nodes. Concomitant with the development of catheter ablation techniques for the treatment of atrial arrhythmias, there is renewed interest in the morphologic arrangement of the cardiac conduction system. In this article, we revisit the anatomy of the specialized tissues, making special reference to the descriptions given at the time of their discovery. According to criteria for histologic distinction of morphologically specialized tracts set nearly 100 years ago, the penetrating bundle (of His) and the ventricular bundle branches are tracts of specialized cells encased by insulating sheaths of fibrous tissue. In contrast, the sinus and AV nodes are recognized histologically but are not insulated from the working atrial myocardium. At its distal extent, the AV node is distinguished from the penetrating bundle not so much by cellular characteristics, but by the presence of a fibrous collar that surrounds the specialized cells. At the atrial part, a zone of histologically transitional cells interposes between the compact node and the working atrial myocardium. Transitional cells enter the triangle of Koch to join the compact node from superiorly, inferiorly, posteriorly, and from the left. Transitional cells of the sinus node, in contrast, are limited to short tongues that interdigitate with musculature of the terminal crest. Apart from a variable extension of its tail, there are no prominent histologically discrete extensions from the sinus node into the working atrial musculature. The internodal myocardium does not contain discrete conducting tracts comparable with the ventricular bundle branches. Preferential conduction more likely reflects the arrangement of the working internodal cells and their related cellular properties.
T Wave Alternans as a Predictor of Recurrent Ventricular Tachyarrhythmias in ICD Recipients: Prospective Comparison with Conventional Risk Markers
Authors: HOHNLOSER STEFAN H. , KLINGENHEBEN THOMAS , LI YI‐GANG , ZABEL MARKUS , PEETERMANS JOY , COHEN RICHARD J.
Published: April 2007

T Wave Alternans for Risk Stratification. Introduction: The current standard for arrhythmic risk stratification is electrophysiologic (EP) testing, which, due to its invasive nature, is limited to patients already known to be at high risk. A number of noninvasive tests, such as determination of left ventricular ejection fraction (LVEF) or heart rate variability, have been evaluated as additional risk stratifiers. Microvolt T wave alternans (TWA) is a promising new risk marker. Prospective evaluation of noninvasive risk markers in low‐ or moderate‐risk populations requires studies involving very large numbers of patients, and in such studies, documentation of the occurrence of ventricular tachyarrhythmias is difficult. In the present study, we identified a high‐risk population, recipients of an implantable cardioverter defibrillator (ICD), and prospectively compared microvolt TWA with invasive EP testing and other risk markers with respect to their ability to predict recurrence of ventricular tachyarrhythmias as documented by ICD electrograms.

Methods and Results: Ninety‐five patients with a history of ventricular tachyarrhythmias undergoing implantation of an ICD underwent EP testing, assessment of TWA, as well as determination of LVEF, baroreflex sensitivity, signal‐averaged ECG, analysis of 24‐hour Holter monitoring, and QT dispersion from the 12‐lead surface ECG. The endpoint of the study was first appropriate ICD therapy for electrogram‐documented ventricular fibrillation or tachycardia during follow‐up. Kaplan‐Meier survival analysis revealed that TWA (P < 0.006) and LVEF (P < 0.04) were the only significant univariate risk stratifiers. EP testing was not statistically significant (P < 0.2). Multivariate Cox regression analysis revealed that TWA was the only statistically significant independent risk factor.

Conclusions: Measurement of microvolt TWA compared favorably with both invasive EP testing and other currently used noninvasive risk assessment methods in predicting recurrence of ventricular tachyarrhythmias in ICD recipients. This study suggests that TWA might also be a powerful tool for risk stratification in low‐ or moderate‐risk patients, and needs to he prospectively evaluated in such populations.
Comparison of ECG Variables of Dispersion of Ventricular Repolarization with Direct Myocardial Repolarization Measurements in the Human Heart
Authors: ZABEL MARKUS , LICHTLEN PAUL R. , HAVERICH AXEL , FRANZ MICHAEL R.
Published: April 2007

Validation of ECG Variables of Dispersion. Introduction: QT dispersion (QTD) from the 12‐tead ECG has been widely adopted as a noninvasive index of dispersion of ventricular repolarization (DVR). QTD, however, has never been validated by direct comparison with myocardial DVR in the human heart.

Methods and Results: Monophasic action potential (MAP) recordings obtained in an earlier study were retrospectively matched with 12‐lead ECGs available from within 24 hours of the invasive procedure. MAPs were available from an average of 8 ± 3 left endocardial sites in 4 patients with left ventricular hypertrophy (LVH) and 7 patients with normal ECGs, and 6 ± 2 epicardial sites in 3 patients of each group during normal ventricular activation. Local repolarization time (RT) was determined as MAP duration at 90% repolarization plus the local activation time. Dispersion of RT was calculated as the difference between the earliest and latest RT. ECGs were digitized and analyzed with recently described interactive QTD analysis software. In addition to standard QTD (defined as QTmax– QTmin), all currently proposed ECG dispersion variables were compared and correlated with the invasive measurements of DVR. QTD exhibited a reasonable correlation with dispersion of RT (R = 0.67; P < 0.01). Several other variables designed to measure DVR exhibited a similar, but not better, correlation. Among them, the QT peak/QT end ratio in V3 (R =−0.72; P < 0.01) and averaged over all analyzableleads (R =−0.59; P < 0.01) exhibited a good correlation with dispersion of RT, which was further improved when endocardial measurements were considered alone. T area measures did not correlate with dispersion of RT, but discriminated LVH.

Conclusion: DVR can he assessed by means of a 12‐lead surface ECG. Several of the variables under study exhibit a similar accuracy in determination of true myocardial dispersion of repolarization. Variables involving the terminal part of repolarization, such as the QT peak/QT ratio, even from a single lead, may add to the determination of DVR from the human heart.
New Diagnostic Finding to Assess Para‐Hisian Pacing Observed in a Patient with a Permanent Form of Junctional Reciprocating Tachycardia
Authors: HIRAO KENZO , TOSHIDA NOBUO , KAWABATA MIHOKO , MOTOKAWA KATSUHIKO , SUZUKI FUMIO , HIEJIMA KAZUMASA
Published: April 2007

Morphologic Change During Para‐Hisian Pacing. Para‐Hisian pacing, a useful method to differentiate conduction over an accessory pathway from conduction over the AV node, is assessed essentially by comparing the timing of local atrial electrograms between Hisbundle captured heats and His‐bundle noncaptured heats. We describe the case of a patient with a permanent form of junctional reciprocating tachycardia, in whom an atrial double potential was recorded only during the tachycardia at the right posterior septum. During para‐Hisian pacing, a morphologic change in the atrial electrogram at the posterior septum was also identified, as well as a change in the retrograde atrial sequence. Since the morphologic change of atrial electrograms during para‐Hisian pacing cannot be demonstrated in a patient without an accessory pathway, this new finding could he considered a new additional diagnostic criterion suggesting the presence of an accessory pathway.
The Pediatric Radiofrequency Ablation Registry's Experience with Ebstein's Anomaly
Authors: REICH JONATHAN D. , AULD DEBBIE , HULSE EDWARD , SULLIVAN KEVIN , CAMPBELL ROBERT ,   FOR THE PEDIATRIC ELECTROPHYSIOLOGY SOCIETY
Published: April 2007

Radiofrequency Ablation in Pediatric Ebstein's Anomaly. Introduction: Abnormal anatomy and complex electrophysiology in patients with Ebstein's anomaly of the tricuspid valve may confound attempts at radiofrequency ablation (RFA).

Methods and Results: Data for 65 pediatric Ebstein's patients (9.8 ± 5.4 years, 4 months to 20 years; 39 ± 25 kg, 5.1 to 108 kg) were obtained from the Pediatric Radiofrequency Ablation Registry. The degree of tricuspid regurgitation (DOTR) and the degree of Ebstein's anomaly were assessed with echocardiography/Doppler. Leading indications were drug refractoriness (24 [37%] of 65 patients) and life‐threatening arrhythmia (14 [22%] of 65 patients). For the 65 patients, 82 typical (nondecremental) accessory pathways (APs) (62% right free wall, 34% right septal, and 4% left sided), 17 other supraventricular tachycardias (1 ectopic atrial, 7 AV reentry, 5 Mahaim, and 4 intra‐atrial reentry tachycardias), and 1 ventricular mechanism were mapped. Thirty‐four (52%) of 65 patients had a single AP (21 right free wall, 10 septal, and 3 left); 19 (29%) of 65 patients multiple APs; 6 (9%) of 65 patients a single AP plus a non‐AP mechanism; and 6 (9%) of 65 patients non‐AP mechanism(s) only. REA acute success rates and recurrence rates for right free wall, right septal, and other mechanisms were 79%/32%, 89%/29%, and 75%/27%. Mild DOTR and a body surface area (BSA) ≤ 1.7 m2 independently predicted a better acute success rate. BSA ≤ 1.7 m2 also predicted long‐term success.

Conclusion: In this patient subset, life‐threatening arrhythmias and multiple electrophysiologic mechanisms are commonly encountered during REA. Mild DOTR and a BSA ≥ 1.7 m2 predict a higher acute success rate. While acute success rates are relatively high, recurrence is frequent.
Shortening of the Intraventricular Conduction Time in Premature Ventricular Beats During Ventricular Extrastimulation: Possible Role of Dimensional Shortening of the Conducting Distance During Ventricular Systole
Authors: KASAI HIROI , KAWARA TOKUHIRO , HIEJIMA KAZUMASA , SUZUKI FUMIO
Published: April 2007

Supernormal Intraventricular Conduction. Introduction: Conduction time (CT) is given by the formula: conducting distance divided by conduction velocity. Based on this formula, we hypothesized that CT shortening (i.e., supernormal conduction) may result from dimensional shortening of the distance of impulse propagation, which naturally occurs during ventricular systole.

Methods and Results: To test the above, two separate groups of patients were studied, group A (14 patients) for electrophysiologic study and group B (12 patients) for echocardiographic study. In group A patients, CT from the stimulus artifact to the basal lateral wall of the left ventricle (LV) (S‐LV interval) was measured using right ventricular (RV) apical extrastimulus testing. S‐LV interval shortening in premature RV beats was demonstrated in all 14 patients. The maximum shortening was 20 ± 9 msec (range 10 to 40), and the maximum% shortening was 16%± 6% (7% to 27%). In group B patients with implanted pacemakers, the major (long) and minor (short) axis dimensions of the LV were measured with echocardiography. The major axis dimension was used as an approximate measure of the linear length from the RV apex to the basal lateral wall of LV. The maximum% shortening of the major axis dimensions was 15%± 4%, 16%± 2%, and 11%± 4% during VVI pacing, respectively, at paced cycle lengths of 1,000 (11 patients), 800 (5 patients), and 600 msec (12 patients). The maximum% shortening of the S‐LV intervals was comparable in magnitude with that of the major axis dimensions: 20% versus 15%± 4%, 15%± 7% versus 16%± 2% and 16%± 6% versus 11%± 4%, respectively, at paced cycle lengths of 1,000, 800, and 600 msec. There was also a good temporal correlation between the electrophysiologic (CT shortening) versus echocardiographic (dimensional shortening) parameters. Thus, the intraventricular CT and the major axis dimension of the LV were shortened in a similar magnitude and also at a similar timing in the cardiac cycle.

Conclusion: These findings suggest the possibility that supernormal conduction may result, at least in part, from dimensional shortening of the pathway length of impulse propagation from the stimulating to recording electrodes, which naturally occurs during ventricular systole.
Ability of Activation Recovery Intervals to Assess Action Potential Duration During Acute No‐Flow Ischemia in the In Situ Porcine Heart
Authors: EJIMA JUNICHI , MARTIN DAVID , ENGLE CONNIE , SHERMAN ZOE , KUNIMOTO SATOSHI , GETTES LEONARD S. ,   for the EXPERIMENTAL CARDIOLOGY GROUP UNIVERSITY OE NORTH CAROLINA AT CHAPEL
Published: April 2007

Activation Recovery Intervals During No‐Flow Ischemia. Introduction: The ability to assess transmural changes in action potential duration during acute no‐flow ischemia is essential to an understanding of the tachyarrhythmias that occur in this setting. The purpose of this study was to determine if activation recovery intervals determined from unipolar electrograms would provide this information.

Methods and Results: We recorded simultaneously transmembrane action potentials and unipolar electrograms from sites located as closely together as possible in the center and at the lateral margin of the ischemic zone during acute no‐flow ischemia and correlated the changes in activation recovery intervals obtained from the unipolar electrograms to the changes in action potential duration. We found that the activation recovery intervals provided an accurate measure of the changes in action potential duration during acute no‐flow ischemia provided the electrograms had a well‐defined, single negative component to the QRS complex with a maximum negative dV/dt > 10 V/sec and a single positive component to the T wave having a maximum positive dV/dt > 1.6 V/sec. Electrograms meeting these criteria comprised 90% of the electrograms recorded at the margin of the ischemic zone throughout 60 minutes of no‐flow ischemia. In the center of the ischemic zone, 75% of the recorded electrograms met these criteria for the first 20 minutes of no‐flow ischemia. Thereafter, the percentage declined and after 40 minutes of no‐flow ischemia, none of the electrograms recorded in the center of the ischemic zone met these criteria.

Conclusion: Activation recovery intervals obtained from unipolar electrograms provide an accurate assessment of changes in action potential duration throughout the ischemic zone during acute no‐flow ischemia, provided the characteristics of the electrograms meet specific predetermined criteria.
A Decade of Clinical Trial Developments in Postmyocardial Infarction, Congestive Heart Failure, and Sustained Ventricular Tachyarrhythmia Patients: From CAST to AVID and Beyond
Authors: NACCARELLLI GERALD V. , WOLBRETTE DEBORAH L. , DELL'ORFANO JOSEPH T. , PATEL HEMANTKUMAR M. , LUCK JERRY C.
Published: April 2007

A Decade of Clinical Trials. Multiple trials using antiarrhythmic drugs, pharmacologic therapy, and implantable cardioverter defibrillators have been performed in an attempt to improve survival in patients: (1) postmyocardial infarction; (2) with congestive heart failure, with and without nonsustained ventricular tachycardia; and (3) with sustained ventricular tachycardia and those who have survived an out‐of‐hospital cardiac arrest. This article reviews some of the key findings and limitations of completed and ongoing trials. We also make recommendations for the current treatment of such patients based on the results of these trials.
Long‐Term Evaluation of the Ventricular Defibrillation Energy Requirement
Authors: TOKANO TAKASHI , PELOSI FRANK , ELEMMING MATTHEW , HORWOOD LAURA , SOUZA JOSEPH J. , ZIVIN ADAM , KNIGHT BRADLEY P. , GOYAL RAJIVA , MAN K. CHING , MORADY ERED , STRICKBERGER S. ADAM
Published: April 2007

Defibrillation Energy Requirements. Introduction: Defibrillation energy requirements in patients with nonthoracotomy defibrillators may increase within several months after implantation. However, the stability of the defibrillation energy requirement beyond 1 year has not been reported. The purpose of this study was to characterize the defibrillation energy requirement during 2 years of clinical follow‐up.

Methods and Results: Thirty‐one consecutive patients with a biphasic nonthoracotomy defibrillation system underwent defibrillation energy requirement testing using a step‐down technique (20, 15, 12, 10, 8, 6, 5, 4, 3, 2, and 1 J) during defibrillator implantation, and then 24 hours, 2 months, 1 year, and 2 years after implantation. The mean defibrillation energy requirement during these evaluations was 10.9 ± 5.5 J, 12.3 ± 7.3 J, 11.7 ± 5.6 J, 10.2 ± 4.0 J, and 11.7 ± 7.4 J, respectively (P= 0.4). The defibrillation energy requirement was noted to have increased by 10 J or more after 2 years of follow‐up in five patients. In one of these patients, the defibrillation energy requirement was no longer associated with an adequate safety margin, necessitating revision of the defibrillation system. There were no identifiable clinical characteristics that distinguished patients who did and did not develop a 10‐J or more increase in the defibrillation energy requirement.

Conclusion: The mean defibrillation energy requirement does not change significantly after 2 years of biphasic nonthoracotomy defibrillator system implantation. However, approximately 15% of patients develop a 10‐J or greater elevation in the defibrillation energy requirement, and 3% may require a defibrillation system revision. Therefore, a yearly evaluation of the defibrillation energy requirement may he appropriate.
Characteristics of Sinus Rhythm Electrograms at Sites of Ablation of Ventricular Tachycardia Relative to All Other Sites: A Noncontact Mapping Study of the Entire Left Ventricle
Authors: SCHILLING RICHARD JOHN , DAVIES D. WYN , PETERS NICHOLAS SIMON
Published: April 2007

Noncontact Mappin g of VT During Sinus Rhythm. Introduction: Regions of the diseased ventricle that activate abnormally during sinus rhythm (SR) may be the areas of slow and disorganized conduction that form the diastolic pathway through which reentry may occur during ventricular tachycardia (VT).

Methods and Results: We examined features of electrograms recorded during SR that might indicate a site suitable for ablation of VT using a noncontact mapping system, which enables reconstruction of > 3,000 electrograms. Preablation SR electrogram characteristics at sites of successful radiofrequency ablation (RFA) were examined in 13 patients with 53 VTs. Timing of onset, lateness of activity, electrogram duration, and number of baseline crossing events of reconstructed electrograms at the sites of successful RFA were compared with the electrograms of latest onset, latest activity, longest duration, and most baseline crossing events of all ventricular sites. Onset of activation at sites of successful RFA were 26.9 ± 25.2 msec (mean ± SD) earlier than (and 2.9 ± 1.7 cm away from) the site of latest onset of SR activation. Electrogram duration at sites of successful RFA was 83%± 14.6% of (and 4.3 ± 1.8 cm away from) the longest electrogram. The baseline crossing events at sites of successful RFA were 53%± 22% of (and 4.9 ± 1.9 cm away from) the most fractionated electrogram. The latest activity at sites of successful RFA was 21.6 ± 24.8 msec earlier than (and 4.3 ± 1.6 cm away from) the site of latest activity.

Conclusion: Although the site of latest onset of endocardial activation during SR proved to be the most sensitive indicator, the characteristics of SR electrograms did not usefully predict successful ablation sites.
Acceleration‐Induced Action Potential Prolongation and Early Afterdepolarizations
Authors: BURASHNIKOV ALEXANDER , ANTZELEVITCH CHARLES
Published: April 2007

Acceleration‐Induced Early Afterdepolarizations. Introduction: Precipitation of torsades de pointes (TdP) has been shown to he associated with acceleration of heart rate in both experimental and clinical studies. To gain insight into the cellular mechanism(s) responsible for the initiation of acceleration‐induced TdP, we studied the effect of acceleration of pacing rate in canine left ventricular epicardial, M region, endocardial, and Purkinje fiber preparations pretreated with E‐4031, an IKr blocker known to induce the long QT syndrome and TdP.

Methods and Results: Standard microelectrode techniques were used. E‐4031 (1 to 2 μM) induced early afterdepolarization (EAD) activity in 31 of 36 M cell, 0 of 10 epicardial, 0 of 10 endocardial, and 9 of 12 Purkinje fiber preparations at basic cycle lengths (BCLs) ≥ 800 msec. In 30 of 36 M cells, sudden acceleration from a BCL range of 900 to 4,000 msec to a range of 500 to 1,500 msec induced transient EAD activity if none existed before or increased the amplitude of EADs if already present. Acceleration‐induced augmentation of EAD activity was far less impressive and less readily demonstrable in Purkinje fibers (4/12). In M cells, appearance of EAD activity during acceleration usually was accompanied by an abbreviation of action potential duration (APD). Within discrete ranges of rates in the physiologic range, acceleration caused a transient prolongation of APD in 38% of M cells, whether or not a distinct EAD was generated. Acceleration produced still more dramatic APD prolongation and EADs in M cells after the BCL was returned to the original slow rate. Epicardium and endocardium APD showed little change immediately after acceleration. A decrease of BCL as small as 10% and, in some cases, a single premature heat could promote EAD activity and APD prolongation in some M cells. Ryanodine (1 μM, 10/10), flunarizine (10 μM, 3/6), and low Na (97 vs 129 mM, 5/5) abolished the acceleration‐induced EAD activity and APD prolongation as well as the EAD activity observed at slow rates in M cells pretreated with E‐4031.

Conclusion: Our results suggest that acceleration from an initially slow rate or a single premature beat can induce or facilitate transient EAD activity and APD prolongation in canine ventricular M cell preparations pretreated with an IKr blocker via a mechanism linked to intracellular calcium loading. Our data provide evidence in support of an important contribution of electrogenic Na/Ca exchange current to this process. These acceleration‐induced changes can result in the development of triggered activity as well as a marked dispersion of repolarization in ventricular myocardium and, thus, may contribute to the precipitation of TdP in patients with the congenital (HERG defect) and acquired (drug‐induced) long QT syndrome.
Retrograde Coronary Venous Infusion of Ethanol for Ablation of Canine Ventricular Myocardium
Authors: WRIGHT KATHY N. , MORLEY TRACEY , BICKNELL JEANETTE , BISHOP SANFORD P. , WALCOTT GREGORY P. , KAY G. NEAL
Published: April 2007

Retrograde Coronary Venous Ethanol Infusion for Ablation. Introduction: Permanent cure of reentrant ventricular tachycardia (VT) associated with coronary artery disease is difficult to achieve. Retrograde coronary venous infusion of ethanol for ablation of ventricular myocardium associated with reentrant tachyarrhythmias has several potential advantages, including use of physiologic mapping techniques and production of deeper, wider necrotic zones.

Methods and Results: Nine anesthetized dogs had baseline hemodynamic measurement, left ventriculography, coronary arteriography, occlusive coronary venography, and programmed electrical stimulation of the right ventricular apex and outflow tract. A balloon‐tipped infusion catheter was advanced into a distal coronary venous branch, the balloon slowly inflated, and pure ethanol infused at volumes of 1.5, 3, or 5 cc. Hemodynamic measurements, angiography, ventriculography, and programmed electrical stimulation were repeated immediately and 1 week following ablation. Formalin‐perfused hearts were serially sectioned and lesion volumes determined. Histologic examination of ablation beds then was performed. No significant difference was found in any hemodynamic measurement before or after ablation. Coronary arteriograms and left ventriculograms were unchanged after ablation. Nonsustained VT occurred in eight dogs during ethanol infusion; however, VT was not inducible in any dog before or after ablation. Infusion volumes of 3 cc or more were required to produce transmural lesions.

Conclusion: Retrograde coronary venous infusions of ethanol using a balloon‐tipped infusion catheter were effective in ablating ventricular myocardium. Retrograde chemical ablation did not itself result in inducible VT or adversely affect hemodynamic measurements or coronary arteries. Transmural myocardial necrosis, necessary in the ablation of VT associated with coronary artery disease, can be produced by higher infusion volumes.
Dispersion of Ventricular Repolarization in Left Ventricular Hypertrophy: Influence of Afterload and Dofetilide
Authors: GILLIS ANNE M. , MATHISON HEATHER J. , KULISZ ELZBIETA , LESTER WANDA M.
Published: April 2007

Modulators of APD Dispersion in Hypertrophy.Introduction: Increased dispersion of ventricular repolarization is observed in cardiac hypertrophy and is associated with sudden cardiac death. At present, there is little information about the effects of cardiac hemodynamics and antiarrhythmic drugs on dispersion of repolarization in disease states. We compared the effects of increasing afterload and the Class III antiarrhythmic drug, dofetilide, on dispersion of ventricular repolarization in hypertrophied rabbit hearts to normal rabbit hearts.

Methods and Results: Cardiac hypertrophy was induced in rabbits by abdominal aortic banding. Isolated hearts were studied 49 ± 4 days postsurgery in the working heart mode using a blood‐buffer perfusate. The action potential duration (APD) was measured from eight sites on the epicardium of the heart at low (50 ± 7 mmHg) afterload and high afterload (97 ± 12 mmHg) at baseline and during dofetilide perfusion. APD dispersion, determined as the difference between the maximal and minimal APD, was greater in hypertrophied hearts (42 ± 8 msec) compared with control hearts (26 ± 8 msec,P< 0.05) at baseline and low afterload. Increasing afterload caused a decrease in APD dispersion in hypertrophied hearts (P< 0.05) but not in control hearts, and APD dispersion was similar in hypertrophied hearts (31 ± 9 msec) compared with control hearts (30 ± 9 msec,P= NS). During dofetilide perfusion, APD dispersion remained greater in hypertrophied hearts (60 ± 39 msec) compared with control hearts (30 ± 13 msec,P< 0.05) at low afterload but not high afterload. Increasing afterload caused shortening of the APD in most regions of the control hearts, whereas APD did not shorten significantly in hypertrophied hearts at baseline and tended to increase during dofetilide perfusion. During dofetilide perfusion, the maximal change in APD recorded from the posterior wall of the left ventricle following an increase in afterload was −18 ± 21 msec in control hearts and 7 ± 21 ms in hypertrophied hearts (P< 0.05).

Conclusion: Epicardial APD dispersion decreases in hypertrophied hearts following an increase in afterload, and this response is mediated in part by the absence of afterload‐induced shortening of the APD. This effect may be due in part to aftered responses of the delayed rectifying current to cardiac loading conditions in the setting of cardiac hypertrophy.
New Electrophysiologic Features and Catheter Ablation of Atrioventricular and Atriofascicular Accessory Pathways:
Authors: OKISHIGE KAORU , GOSEKI YOSHINARI , ITOH AKIO , TSUBOI NAOYA , SASANO TETSUO , AZEGAMI KOUJI , OHIRA HIROSHI , YAMASHITA KATSUHIRO , SATAKE SHUTAROU , HIEJIMA KAZUMASA
Published: April 2007

Catheter Ablation for Mahaim Pathways. Introduction: Several modalities of catheter ablation have been proposed to eliminate Mahaim pathway conduction. However, limited research has been reported on the electrophysiologic nature of this pathway in its entity.

Methods and Results: In seven patients, electrophysiologic study was performed, and radiofrequency energy was applied to investigate the electrophysiologic clues for successful ablation. In all seven patients, the Mahaim pathway was diagnosed as a right‐sided atriofascicular or atrioventricular pathway with decremental properties. In two patients, two different kinds of electrograms were recorded through the ablation catheter positioned at the Mahaim pathway location: one was suggestive of conduction over the decremental portion, demonstrating a dulled potential; and the other of nondecremental conduction, demonstrating a spiked potential. All but one of the Mahaim pathways were eliminated successfully at the atrial origin where the spiked Mahaim potential was recorded. Radiofrequency energy application was performed at the slow potential site resulting in failure to eliminate the conduction over the Mahaim pathway. Conduction block at the site between the slow and fast potential recording sites was provoked by intravenous administration of adenosine, concomitant with a decrease in the amplitude of the Mahaim potential. In one patient, the clinical arrhythmia was a sustained monomorphic ventricular tachycardia originating from the ventricular end of the Mahaim fiber.

Conclusion: The identification of Mahaim spiked potentials may be the optimal method to permit their successful ablation. Detailed electrophysiologic assessment is indispensable for successful ablation of tachycardias associated with Mahaim fibers because tachycardias unassociated with Mahaim fibers can occur despite complete elimination of the Mahaim fiber.
Phenylephrine Increases T Wave Shock Energy Required to Induce Ventricular Fibrillation
Authors: MITRANI RAUL D. , MILES WILLIAM M. , KLEIN LAWRENCE S. , ZIPES DOUGLAS P.
Published: April 2007

Phenylephrine Increases VFT. Introduction: Previous reports in experimental models have suggested that ventricular fibrillation threshold (VFT) can be changed by manipulating cardiac neural tone using agents such as phenylephrine. The purpose of this study was to determine whether phenylephrine increased the energy required to induce VF in humans undergoing such induction using DC energy applied to the T wave.

Methods and Results: In this prospective investigation, 18 consecutive patients with previously implanted cardioverter defibrillators had induction of VF by placing DC monophasic shocks into the T wave coupled 310 msec after the eighth paced ventricular complex at 400 msec. The T wave shock energy was titrated from 0.2 to 12 J until sustained VF or ventricular tachycardia was induced. Phenylephrine was infused either before the first or second VF induction in a randomized fashion to increase systolic blood pressure by more than 20 mmHg. The mean energy required to induce VF was 1.1 J at baseline and increased to 1.7 J during phenylephrine infusion (P = 0.036). The mean arterial pressure increased from 88 to 114 mmHg (P < 0.001), and the mean sinus cycle length increased from 850 to 1070 msec (P < 0.001). Ten of 13 (77%) patients with sinus cycle length prolongation bad increased energy requirements to induce VF compared with only 1 of 5 patients (20%) without sinus cycle length prolongation (P < 0.05).

Conclusion: Phenylephrine increases VFT in humans presumably by reflex activation of the baroreceptors decreasing sympathetic and/or increasing parasympathetic cardiac efferent effects.
Why a Large Tip Electrode Makes a Deeper Radiofrequency Lesion:
Authors: OTOMO KENICHIRO , YAMANASHI WILLIAM S. , TONDO CLAUDIO , ANTZ MATTHIAS , BUSSEY JONATHAN , PITHA JAN V. , ARRUDA MAURICIO , NAKAGAWA HIROSHI , WITTKAMPE FRED H.M. , LAZZARA RALPH , JACKMAN WARREN M.
Published: April 2007

Increase in RF Lesion Depth with Larger Electrode. Introduction: Increasing electrode size allows an increase in radiofrequency lesion depth. The purpose of this study was to examine the roles of added electrode cooling and electrode‐tissue interface area in producing deeper lesions.

Methods and Results: In 10 dogs, the thigh muscle was exposed and superfused with heparinized blood. An 8‐French catheter with 4‐ or 8‐mm tip electrode was positioned against the muscle with a blood flow of 350 mL/min directed around the electrode. Radiofrequency current was delivered using four methods: (1) electrode perpendicular to the muscle, using variable voltage to maintain the electrode‐tissue interface temperature at 60°C; (2) same except the surrounding blood was stationary; (3) perpendicular electrode position, maintaining tissue temperature (3.5‐mm depth) at 90°C; and (4) electrode parallel to the muscle, maintaining tissue temperature at 90°C. Electrode‐tissue interface temperature, tissue temperature (3.5‐ and 7.0‐mm depths), and lesion size were compared between the 4‐ and 8‐mm electrodes in each method. In Methods 1 and 2, the tissue temperatures and lesion depth were greater with the 8‐mm electrode. These differences were smaller without blood flow, suggesting the improved convective cooling of the larger electrode resulted in greater power delivered to the tissue at the same electrode‐tissue interface temperature. In Method 3 (same tissue current density), the electrode‐tissue interface temperature was significantly lower with the 8‐mm electrode. With parallel orientation and same tissue temperature at 3.5‐mm depth (Method 4), the tissue temperature at 7.0‐mm depth and lesion depth were greater with the 8‐mm electrode, suggesting increased conductive heating due to larger volume of resistive heating because of the larger electrode‐tissue interface area.

Conclusion: With a larger electrode, both increased cooling and increased electrode‐tissue interface area increase volume of resistive heating and lesion depth.
Differential Effects of Quinidine, Flecainide, and Cibenzoline on Anisotropic Conduction in the Isolated Porcine Heart
Authors: LACROIX DOMINIQUE , DELFAUT PHILIPPE , ADAMANTIDIS MONIQUB , CARDINAL RENÉ , KLUG DIDIER , KACET SALEM , DUPUIS BERNARD
Published: April 2007

Differential Drug Effects on Anisotropic Conduction. Introduction:Anisotropic conduction characteristics, expressed as the ratio of conduction velocities in the longitudinal (Vl) and transverse (Vt) fiber directions, may play a role in the mechanism of some ventricular tachycardias and is influenced by pharmacologic interventions. Discrepancies exist among the reported orientation‐dependent effects of available Class I antiarrhythmic drugs. The aim of this study was to assess the respective effects of quinidine (Class IA), flecainide (Class IC), and cibenzoline (not subclassifled) on the anisotropic conduction of porcine hearts, in corroboration of their effects on ventricular action potentials.

Methods and Results: We studied the actions of 3 and 10 μM quinidine, 1 and 3 μM flecainide, and 0.3 and 1 μM cibenzoline on Vl and Vt determined from 128 electrograms recorded with a plaque electrode on the anterior left ventricle of isolated perfused hearts (spacing 2.5 mm). Vl and Vt were computed from isochronal maps displaying ellipsoid activation during stimulation from the center of the plaque. The effects on the maximal rate of depolarization (V˙max) of action potentials were obtained from ventricular muscle exposed to the same drugs. Flecainide [1 μM] and cibenzoline [0.3 μM] did not alter Vl, and Vt, significantly. Quinidine [3 μM] predominantly depressed Vl at rapid pacing rates, hut the Vl/Vt ratio was not significantly altered. Quinidine [10 μM] and flecainlde [3 μM] reduced Vl and Vt in a frequency dependent fashion. Conversely, cibenzoline [1 μM] mostly decreased Vl and thus decreased the Vl/Vt ratio and increased the Vl/Vt at all pacing rates. This different effect was not related to a greater depressant effect on V˙max.

Conclusion: Quinidine and flecainide act similarly on the anisotropic pattern of conduction (both drugs increase the Vl/Vt ratio), whereas cibenzoline exerts opposite effects. Orientation dependent effects are different among Class I antiarrhythmic drugs and may be of importance in their therapeutic efficacy or proarrhythmic potential.
Increased Dispersion of Repolarization Time Determined by Monophasic Action Potentials in Two Patients with Familial Idiopathic Ventricular Fibrillation
Authors: MATSUO KIYOTAKA , SHIMIZU WATARU , KURITA TAKASHI , SUYAMA KAZUHIRO , AIHARA NAOHIKO , KAMAKURA SHIRO , SHIMOMURA KATSURO
Published: April 2007

Increased Dispersion of RT in Familial Idiopathic VF. Introduction: The role of increased dispersion of repolarization in the genesis of torsades de pointes in patients with long QT syndrome has been clarified, but its role in the genesis of idiopathic ventricular fibrillation (VF) is not yet known. To investigate the pathogenesis of VF, we recorded monophasic action potentials (MAPs) from two siblings (48‐ and 36‐year‐old males) with familial idiopathic VF.

Methods and Results: The elder brother (patient I) showed a late r’ wave in lead V1 and ST segment elevation in leads V1 through V3. The younger brother (patient 2) had late r’ waves and ST segment elevation in leads II, III, and aVF, and the configurations were very similar to those of patient I. MAPs were recorded from several sites in the right ventricular (RV) and left ventricular (LV) endocardium during constant right atrial pacing. The repolarization time (RT) was defined as the sum of the activation time (AT) and action potential duration (APD) at 90% repolarization. In patient 1, marked prolongation of the AT (140 msec) and the RT (380 msec) was recorded in the RV septum of the outflow tract, and the RT dispersion was markedly increased (125 msec). In contrast, patient 2 showed prolongation of the AT (80 msec) and RT (310 msec), and fractionated electrograms in the RV floor of the inflow tract. The RT dispersion was also increased (80 msec). VF and nonsustained polymorphic ventricular tachycardia were induced by double premature stimulation in patients 1 and 2, respectively. Chronic amiodarone therapy decreased the RT dispersion and suppressed the induction of ventricular tachyarrhythmias in patient 2, although late r’ waves and slight ST segment elevation were unmasked in leads V1, and V2.

Conclusion: Our data suggest that the increased dispersion of the RT, which was due mainly to a localized conduction delay in the RV, created an arrhythmogenic substrate in the two patients with familial idiopathic VF.
Molecular Genetic Basis of Hypertrophic Cardiomyopathy:
Authors: MARIAN ALI J. , ROBERTS ROBERT
Published: April 2007

Genetics of SCD in HCM. Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease caused by mutations in sarcomeric proteins. The disease is characterized by left ventricular hypertrophy in the absence of an increased external load, and myofibrillar disarray. A large number of mutations in genes coding for the β‐myosin heavy chain (β‐MyHC), cardiac troponin T (cTnT), cardiac troponin I, α‐tropomyosin, myosin binding protein C (MyBP‐C), and myosin light chain 1 and 2 in patients with HCM have been identified. Genotype‐phenotype correlation studies have shown that mutations carry prognostic significance. The Gly256Glu, Val606Met, and Leu908Val mutations in the μ‐MyHC are associated with a benign prognosis. In contrast, Arg403Gln, Arg719Trp, and Arg453Cys mutations are associated with a high incidence of sudden cardiac death (SCD). Mutations in cTnT are associated with a mild degree of hypertrophy, but a high incidence of SCD. Mutations in MyBP‐C are associated with mild hypertrophy and a benign prognosis. However, it has become evident that factors other than the underlying mutations, such as genetic background and possibly environmental factors, also modulate phenotypic expression of HCM.
Multiple Components in the Unipolar Electrogram: A Simulation Study in a Three‐Dimensional Model of Ventricular Myocardium
Authors: TACCARDI BRUNO , VERONESE SILVIA , FRANZONE PIERO COLLI , GUERRI LUCIANO
Published: April 2007

Multiple Components in the Unipolar Electrogram. Introduction: For many decades, the interpretation of unipolar electrograms (EGs) and ECGs was based on simple models of the heart as a current generator, e.g., the uniform dipole layer, and, more recently, the “oblique dipole layer.” However, a number of recent and old experimental data are inconsistent with the predictions of these models. To address this problem, we implemented a numerical model simulating the spread of excitation through a parallelepipedal myocardial slab, with a view to identifying the factors that affect the shape, amplitude, and polarity of unipolar EGs generated by the spreading wavefront.

Methods and Results: The numerical model represents a portion of the left ventricular wall as a parallelepipedal slab (6.5 × 6.5 × 1 cm); the myocardial tissue is represented as an anisotropic bidomain with epi‐endocardial rotation of fiber direction and unequal anisotropy ratio. Following point stimulation, excitation times in the entire volume are computed by using an eikonal formulation. Potential distributions are computed by assigning a fixed shape to the action potential profile. EGs at multiple sites in the volume are computed from the time varying potential distributions. The simulations show that the unipolar QRS waveforms are the sum of a “field” component, representing the effect of an approaching or receding wavefront on the potential recorded by a unipolar electrode, and a previously unrecognized “reference” component, which reflects the drift, during the spread of excitation, of the reference potential, which moves from near the positive to near the negative extreme of the potential distribution during the spread of excitation.

Conclusion: The drift of the reference potential explains the inconsistencies between the predictions of the models and the actual shapes of the EGs. The drift modifies the slopes of EG waveforms during excitation and recovery and can be expected to affect the assessment of excitation and recovery times and QRS and ST‐T areas. Removing the drift reestablishes consistency between potential distributions and electrographic waveforms.