bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective Evaluation of the Effect of Biphasic Waveform Defibrillation on Ventricular Pacing Thresholds
Authors: KUDENCHUK PETER J. , POOLE JEANNE E. , DOLACK G. LEE , GLEVA MARYE J. , ANDERSON JILL , TROUTMAN CHARLES , BARDY GUST H.
Published: April 2007

Effect of Defibrillation on Pacing Thresholds. Introduction: Significant increases in ventricular pacing threshold have been observed following monophasic waveform ventricular defibrillation shocks. High‐output pacing is recommended to ensure consistent capture, particularly in pacemaker‐dependent patients who are likely to be defibrillated. Whether biphasic waveform defibrillation compounds this problem is not known. The purpose of this prospective study was to examine serial changes in ventricular pacing thresholds following single, multiple, low‐ and high‐energy biphasic defibrillation sbocks from an implanted defibrillator.

Methods and Results: Bipolar pacing thresholds before and after defibrillation, and the adequacy of pacing capture at three times preshock threshold in the immediate aftermath of ventricular defibrillation, were prospectively evaluated in 67 consecutively tested recipients of a biphasic implanted cardioverter defibrillator. Overall, serial pacing thresholds following successful defibrillation were completely unchanged after 141 of 177 (80%) ventricular fibrillation inductions. In no case did the threshold pulse width increment > 0.06 msec from its baseline value after shock, nor did pacing at a pulse width of three times preshock threshold from dedicated bipolar pacing electrodes fail to result in successful ventricular capture. Changes in threshold were not related to when measured from the time of shock, defibrillation energy, number of shocks, electrode system, chronicity of leads, shock orientation, or to clinical factors.

Conclusions: No clinically important changes in pacing threshold were observed after biphasic waveform defibrillation. Bradycardia pacing at conventional pacemaker outputs of three times baseline pulse width threshold from bipolar electrodes dedicated exclusively to pacing or sensing (but not defibrillation) consistently allowed for an adequate safety margin following defibrillation.
Effect of Waveform Tilt on Defibrillation Thresholds in Humans
Authors: SHOROFSKY STEPHEN R. , FOSTER ANDREW H. , GOLD MICHAEL R.
Published: April 2007

Effect of Tilt on Defibrillation Threshold. Introduction: Despite the common use of the implantable cardioverter defibrillator to treat patients with life‐threatening ventricular arrhythmias, the mechanism of defibrillation and the optimal waveform for implanted devices are poorly understood. All of the currently available pulse generators deliver exponentially declining pulses that are either automatically or manually truncated to achieve tilts of about 50% to 65%. Although this value was chosen based on experimental animal data, several theoretical models have been developed to describe defibrillation, which raise into question this choice of waveform shape. Accordingly, the present study was designed to test the effect of waveform tilt on defibrillation efficacy in humans.

Methods and Results: Twenty‐three patients undergoing cardioverter defibrillator implantation were studied. Monophasic defibrillation thresholds (DFTs) were measured using a single reversal protocol at 35%, 50%, 65%, and 80% tilts by altering the pulse width of the shock. Mean defibrillation impedance was 41 ± 6 Ω. The DFT, measured by either leading‐edge voltage or stored energy, was insensitive to altering the waveform tilt from 50% to 80%, only increasing when the tilt was reduced to 35%. A tilt of 65% yielded the lowest DFT voltage in only 8 of 23 patients. Significantly lower DFTs (≥ 40 V) were obtained using other tilts in seven patients. When the relationship between average current and pulse width was fit with a Weiss‐Lapicque model, the data yielded a mean chronaxie of 4.6 ± 3.0 msec and a rheobase of 4.2 ± 1.7 A, but considerable patient variability was observed.

Conclusion: On average, DFTs in humans are insensitive to altering monophasic waveform tilts between 50% and 80%. There is, however, considerable patient variability, raising into question the premise that a single defibrillator waveform tilt is best for all patients.
Transhepatic Access to the Atrioventricular Ring for Delivery of Radiofrequency Energy
Authors: FISCHBACH PETER , CAMPBELL ROBERT M. , HULSE EDWARD , MOSCA RALPH , ARMSTRONG BRIAN , LLOYD THOMAS R. , DICK MACDONALD
Published: April 2007

Transhepatic Ablation. Introduction: Transcatheter radiofrequency ablation is an effective, safe treatment of arrhythmias in children. However, despite technical advances, patients with obstructed venous access to the heart have not been candidates for this treatment.

Methods and Results: Two children (8.2 and 10.9 kg) with complex congenital heart disease, supraventricular tachycardia, and obstructed venous access underwent successful radiofrequency ablation of either a right (one patient) or left (one patient) accessory pathway using the transhepatic route to the heart.

Conclusion: This experience underscores the usefulness of the transhepatic approach in small patients, in patients with limited venous access, and in patients with complex congenital heart disease.
Sawtooth First Phase Biphasic Defibrillation Waveform
Authors: YAMANOUCHI YOSHIO , BREWER JAMES E. , MOWREY KENT A. , KROLL MARK W. , DONOHOO ANN M. , WILKOFF BRUCE L. , TCHOU PATRICK J.
Published: April 2007

“Sawtooth First Phase” Biphasic Waveform. Introduction: A major limitation in a conventional truncated exponential waveform is the rapid drop in current that results in short duration of high current or longer duration with a lower average current. We hypothesized that increasing the first phase average current by boosting the decaying waveform prior to phase reversal may improve defibrillation efficacy.

Methods and Results: To better simulate a “rectangular” waveform during the first phase, a “sawtooth” defibrillation waveform was constructed using “parallel‐series” switching of capacitances (each 30 μF) during the first phase. This permitted a boost in the voltage late in the first phase. This sawtooth hiphasic waveform (sawtooth) was compared to two clinical waveforms: a 135‐μF capacitance (control‐1) and a 90‐μF capacitance (control‐2) waveform. Defibrillation threshold (DFT) parameters were evaluated in 13 anesthetized pig models using a system consisting of a transvenous right ventricular apex lead (anode) and a left pectoral ldquo;hot can” electrode (cathode) system. DFT was determined by a “down‐up down‐up” protocol. The stored energy for sawtooth, control‐1, and control‐2 was 10.5 ± 2.8 J, 12.3 ± 3.7 J*, and 12.2 ± 2.8 J*, respectively (*P < 0.01 vs sawtooth). The average current of the first phase for sawtooth, control‐1, and control‐2 was 7.6 ± 1.3 A, 4.7 ± 0.9 A*, and 6.2 ± 0.9 A*, respectively (*P = 0.0001 vs sawtooth).

Conclusion: A sawtooth biphasic waveform utilizing a “parallel‐series” switching system of smaller capacitors can improve defibrillation efficacy. A higher average current in the first phase generated by such a waveform may contribute to more efficient defibrillation by facilitating myocyte capture.
Simulated Internal Defibrillation in Humans Using an Anatomically Realistic Three‐Dimensional Finite Element Model of the Thorax
Authors: KINST THOMAS F. , SWEENEY MICHAEL O. , LEHR JOHN L. , EISENBERG SOLOMON R.
Published: April 2007

Finite Element Modeling of Defibrillation. Introduction: Determination of the optima) electrode configuration during implantable cardioverter defibrillator (ICD) implantation remains largely an empirical process. This study investigated the feasibility of using a finite element model of the thorax to predict clinical defibrillation metrics for internal defibrillation in humans. Computed defibrillation metrics from simulations of three common electrode configurations with a monophasic waveform were compared to pooled metrics for similar electrode and waveform configurations reported in humans.

Methods and Results: A three‐dimensional finite element model was constructed from CT cross‐sections of a human thorax. Myocardial current density distributions for three electrode configurations (epicardial patches, right ventricular [RV] coil/superior vena cava [SVC] coil, RV coil/SVC coil/subcutaneous patch) and a truncated monophasic pulse with a 65% tilt were simulated. Assuming an inexcitability threshold of 25 mA/cm2 (10 V/cm) and a 75% critical mass criterion for successful defibrillation, defibrillation metrics (interelectrode impedance, defibrillation threshold current, voltage, and energy) were calculated for each electrode simulation. Values of these metrics were within 1 SD of sample‐size weighted means for the corresponding metrics determined for similar electrode configurations and waveforms reported in human clinical studies. Simulated myocardial current density distributions suggest that variations in current distribution and uniformity partially explain differences in defibrillation energy requirements between electrode configurations.

Conclusion: Anatomically realistic three‐dimensional finite element modeling can closely simulate internal defibrillation in humans. This may prove useful for characterizing patient‐specific factors that influence clinically relevant properties of current density distributions and defibrillation energy requirements of various ICD electrode configurations.
Regional Gradation of L‐Type Calcium Currents in the Feline Heart with a Healed Myocardial Infarct
Authors: PINTO JUDITH M.B. , YUAN FENG , WASSERLAUE BERNARD J. , BASSETT ARTHUR L. , MYERBURG ROBERT J.
Published: April 2007

ICa in Healed Myocardial Infarction. Introduction: Abnormal action potentials in myocytes adjacent to > 2‐month‐uld feline LV myocardial infarcts (MI) may reflect alterations in Ca2+ currents (ICa).

Methods and Results: We compared ICa, at 36°C, in subendocardial myocytes isolated from areas adjacent to MI and to ICa in cells from remote areas (> 4 mm away; REM) and control cells from similar regions in normal hearts. Control (CON) myocytes had membrane capacitance of 234 ± 10 pF (n = 81 cells) compared to 305 ± 14 pF in REM (71 cells; P < 0.05 from CON) and 237 ± 11 pF (n = 55 cells) in MI (not different from CON). From Vh=−40 mV, peak ICa elicited by test potentials (−35 to +70 mV) were significantly larger in CON (−1746 ± 123 pA) and REM (−1795 ± 142 pA) compared to Ml (−1352 ± 129 pA) (P < 0.05). Peak 1(11 density was significantly reduced in REM (−6.0 ± 0.4 pA/pF) or MI (−5.7 ± 0.4 pA/pF, P < 0.05) compared to CON (−7.5 ± 0.4 pA/pF). Double exponential ICa decay was similar among groups. Half‐inactivation potential (V0.5) was significantly shifted (hyperpolarizing direction) for MI (−29.1 ± 2.6 mV) and REM (−24.6 ± 1.2 mV) myocytes compared to −20.3 ± 1.0 mV in CON. MI slope factor (k; 9.0 ± 0.5) was significantly different from CON (6.8 ± 0.3) and RKM (7.3 ± 0.4). No differences in time course of recovery from inactivation were noted. Five millimolar Ba2+0 produced significant increases in ICa in CON and REM but an attenuated response in MI. Bay k8644 (1 μM) produced similar ICa increase in all groups. ICa increase due to isoproterenol (1 ICaM) in MI and REM was half that in CON, but there were no differences in increased ICa responses among groups following phenylephrine (10 μM).

Conclusion: Reduced ICa density in REM reflects cell hypertrophy, whereas altered ICa of MI may reflect altered channel structure and/or function.
The Effects of Isoproterenol on the Cardiac Conduction System
Authors: COSSÚ SERGIO F. , ROTHMAN STEVEN A. , CHMIELEWSKI I. LISA , HSIA HENRY H. , VOGEL R. LEE , MILLER JOHN M. , BUXTON ALFRED E.
Published: April 2007

Dose‐Dependent Effects of Isoproterenol. Introduction: Isoproterenol is used to assess and facilitate AV nodal conduction, and thus potentiate the induction of supraventricular arrhythmias. It is commonly administered in increasing doses until a predetermined decrease in sinus cycle length, usually 20% to 30%, occurs. This regimen may result in undesirable side effects. We have observed that effects of isoproterenol on the AV node may occur prior to achieving the target sinus cycle length. The purpose of this study was to determine whether the sinus and AV nodes have equal sensitivity to isoproterenol.

Methods and Results: Thirty‐eight consecutive patients, who underwent electrophysiologic evaluation for a variety of indications, were given incremental doses of isoproterenol at 0.007, 0.014, 0.021, and 0.028 μ/g/kg per minute. Sinus cycle length and AV node function were assessed at baseline and after 5 minutes at each dose. The percent change from baseline in AV node function was compared with the change in sinus cycle length at each dose interval. Significantly greater decreases were observed in the anterograde and retrograde AV nodal Wenckebach cycle length (P < 0.0001) than in the sinus cycle length at the lowest isoproterenol dose (0.007 fig/kg per min). These differences were not apparent at higher doses. A sustained supraventricular tachycardia was inducible in 15 of 38 patients in the presence of isoproterenol, of which 40% occurred at the lowest dose.

Conclusions: The AV node is more sensitive than the sinus node to the effects of isoproterenol. Lower doses of isoproterenol than those commonly used may often facilitate the induction of a supraventricular tachyarrhythmia, thus reducing side effects.
Adenosine‐Sensitive Atrial Reentrant Tachycardia Originating from the Atrioventricular Nodal Transitional Area
Authors: IESAKA YOSHITO , TAKAHASHI ATSUSHI , GOYA MASAHIKO , SOEJIMA YOHKOH , OKAMOTO YOSHIHIRO , FUJIWARA HIDEOMI , AONUMA KAZUTAKA , NOGAMI AKIHTKO , HIROE MICHIAKI , MARUMO FUMIAKI , HIRAOKA MASAYASU
Published: April 2007

Adenosine‐Sensitive AT from AVN Area. Introduction: Atrial tachycardia shows wide variations in its electrophysiologic properties and sites of origin. We report an atrial tachycardia with ECG manifestations and electrophysiologic characteristics similar to an atypical form of AV nodal reentrant tachycardia (AVNRT).

Methods and Results: This supraventricular tachycardia was observed in 11 patients. It was initiated by atrial extrastimulation with an inverse relationship between the coupling interval of an extrastimulus and the postextrastimulus interval. Its induction was not related to a jump in the AH interval, and its perpetuation was independent of conduction block in the AV node. Ventricular pacing during tachycardia demonstrated AV dissociation without affecting the atrial cycle length. A very small dose of adenosine triphosphate (mean 3.9 ± 1.2 mg) could terminate the tachycardia. The earliest atrial activation during tachycardia was recorded at the low anteroseptal right atrium with a different intra‐atrial activation sequence from that recorded during ventricular pacing, where the tachycardia was successfully ablated in 9 of 10 attempted patients. Bidirectional AV nodal conduction remained unatttched after successful ablation.

Conclusion: There may he an entity of adenosine‐sensitive atrial tachycardia probably due to focal reentry within the AV node or its transitional tissues without involvement of the AV nodal pathways. This tachycardia can he ablated without disturbing AV nodal conduction from the right atrial septum.
Developmental Changes in Modulation of Cardiac Repolarization by Sympathetic Stimulation: The Role of Beta‐ and Alpha‐Adrenergic Receptors
Authors: CUA MARK , SHVILKIN ALEXEI , DANILO PETER , ROSEN MICHAEL R.
Published: April 2007

Sympathetic Modulation of Cardiac Repolarization. Introduction: Our goals were to study the role of development in determining the cardiac effects of sympathetic neural activation, and to identify the roles of α‐ and β‐adrenergic receptor‐mediated pathways in modulating the effects of sympathetic stimulation.

Methods and Results: We compared responses of young and adult canine hearts in situ to right, left, and bilateral stellate ganglion stimulation. We focused on changes in heart rate, rhythm, QT interval, rate‐corrected QT interval (QT), and T wave amplitude. Right stellate stimulation (RSS) induced more pronounced sinus tachycardia in adult than young animals. Left stellate stimulation (LSS) Induced junctional tachycardia in adult more than young animals. In adults, LSS and RSS prolonged QTc (LSS > RSS). whereas 1‐week‐olds manifested QTc shortening with RSS. LSS also increased T wave amplitude, most markedly in adults. In all studies, bilateral stellate stimulation induced responses intermediate between those seen with RSS and LSS. β‐Adrenergic blockade (propranolol) aholished all responses to LSS in adult hearts, but α‐blockade (prazosin) attenuated only the LSS‐induced prolongation in QTc.

Conclusion: In the postnatal modulation of cardiac rhythm, rate, and repolarization by the sympathetic nervous system, β‐adrenergic receptors play a major role at all ages, whereas α‐adrenergic receptors play a lesser role, which is manifested only in adults. Moreover, expression of junctional tachycardias, which are β‐adrenergically modulated, is seen only in the adults.
Decreased Density of Ito in Left Ventricular Myocytes from German Shepherd Dogs with Inherited Arrhythmias
Authors: FREEMAN LISA C. , PACIORETTY LINDA M. , MOISE N. SYDNEY , KASS ROBERT S. , GILMOUR ROBERT F.
Published: April 2007

Decreased Ito in Dogs with Inherited Arrhythmias.
Introduction: A colony of inbred German shepherd dogs with inherited ventricular arrhythmias has been established.

Methods and Results: The inward rectifier (IKI), the slow delayed rectifier (IKs), and the transient outward current (IKI) were recorded from epicardial myocytes, and IKI, was recorded from Purkinje myocytes isolated from the left ventricles of dogs mildly or severely affected with arrhythmias, and unaffected relatives. There were no differences between unaffected and severely affected dogs in the densities of either IKI or IKI. Peak Ito density at +1–40 mV was reduced by 49% in epicardial myocytes from severely affected dogs. Ito density was also reduced in a subset of Purkinje myocytes. Boltzmann analysis of steady‐state inactivation showed no differences between groups in slope factor. V1/2 the half‐inactivation voltage, was shifted by +6.2 mV in epicardial cells from severely affected versus unaffected dogs. In addition, the time constant for Ito decay was reduced in mildly and severely affected dogs compared to unaffected dogs.

Conclusion: Altered density and inactivation of Ito are associated with the presence of severe ventricular arrhythmias in inbred dogs at risk for sudden death.
The Ventricular Defibrillation and Upper Limit of Vulnerability Dose‐Response Curves
Authors: MALKIN ROBERT A. , SOUZA JOSEPH J. , IDEKER RAYMOND E.
Published: April 2007

DF and ULV Dose‐Response Curves. Introduction: A stimulus delivered in the T wave of a paced cardiac cycle can induce ventricular fibrillation (VF). If the stimulus strength is increased, the probability of inducing VF decreases. This study determines an ideal mathematical model (a dose‐response curve) for the relationship between the shock strength and the probability of inducing VF or defibrillating.

Methods and Results: Defibrillating electrodes were implanted in the right ventricle and superior vena cava in 16 pigs. The electrode in the vena cava was electrically connected to a cutaneous patch. The same electrodes were used for both VF induction and defibrillation. T wave stimuli were given at the peak of the T wave according to a modified up‐down protocol (40 V up, 20 V down). When a T wave stimulus induced VF, a defibrillation stimulus was delivered 10 seconds later, also according to the modified up‐down protocol. Exponential, logistic, log‐dose logistic, piecewise linear, and Box‐Tiao dose‐response curves were fit to the resulting data using the maximum likelihood method. For the defibrillation data, it was found that only the logistic and Box‐Tiao curves fit all of the animals (P < 0.05). For VF induction, only the Box‐Tiao curve fit all of the animals (P < 0.05). Extrapolating along a dose‐response curve that did not fit to a shock strength with a very low probability of inducing VF or a very high probability of defibrillating yielded errors as great as 610 V.

Conclusion: The Box‐Tiao dose‐response curve is the best single choice for fitting VF induction or defibrillation datasets
Transcoronary Venous Radiofrequency Catheter Ablation of Ventricular Tachycardia
Authors: STELLBRINK CHRISTOPH , DIEM BJÖRN , SCHAUERTE PATRICK , ZIEGERT KATHRIN , HANRATH PETER
Published: April 2007

Coronary Venous Ablation of VT. Ventricular tachycardias in coronary artery disease arise mostly from endocardial sites. However, little is known about the site of origin in other diseases. We present the case of an incessant, adenosine‐sensitive ventricular tachycardia arising from the lateral wall of the left ventricle in a patient with mildly reduced left ventricular function. Intracardiac mapping suggested an epicardial origin, and the tachycardia was successfully ablated from a coronary sinus branch. After ablation, left ventricular function returned to normal. Transcoronary venous radiofrequency catheter ablation is a new approach for the treatment of ventricular tachycardia. Its value in the management of other types of ventricular tachycardia has yet to he determined.
Implantable Cardioverter Defibrillator Utilization Among Device Recipients Presenting Exclusively with Syncope or Near‐Syncope
Authors: MILITIANU ARIE , SALACATA ABRAHAM , SEIBERT KAREN , KEHOE RICHARD , BAGA JOHN J. , MEISSNER MARC D. , PIRES LUIS A. , SCHUGER CLAUDIO D. , STEINMAN RUSSELL T. , MOSTELLER ROBERT D. , PALTI AMOS J. , BEN DAVID JOSEPH , LESSMEIER TIMOTHY J. , LEHMANN MICHAEL H.
Published: April 2007

ICD Use in Syncope. Introduction: Implantable cardioverter defibrillators (ICDs) are occasionally used in presumed high‐risk patients with electrocardiographically undocumented syncope, although the incidence of ventricular tachyarrhythmias in this population is not well defined.

Methods and Results: We studied 33 consecutive patients receiving; an ICD (67% nonthoracotomy and 70% tiered therapy) after electrophysiologic testing for unmonitored “syncope” (n = 29) or “near‐syncope” (n = 4). Atherosclerotic heart disease was present in 24 (73%); mean left ventricular ejection fraction (LVEF) was 0.39 ± 0.15; and sustained monomorphic ventricular tacycardia (SMVT) was inducible in 18 (55%). Over a median follow‐up of 17 months (range 4 to 61), 12 patients (36%) received ≥ 1 appropriate ICD discharge triggered by SMVT (cycle length 230 lo 375 msec) in 10 and ventricular Mutter or fibrillation in 2—without concomitant antiarrhythmic medication in 8 of 12 cases, Inducible SMVT and LAEF ≤ 0.35 were statistically significant, independent predictors of an appropriate ICD discharge (P < 0.02 and P < 0.03, respectively). Estimated 1‐year cumulative survival free of appropriate discharge was 34% versus 87%, respectively, in patients with versus without inducible SMVT (P < 0.02), and 18% versus 56%, respectively, in patients with LVEF ≤ 0.35 versus LVEF > 0.35 (P < 0.03).

Conclusion: In this highly select, multicenter population of ICD recipients with electrocardiographically undocumented syncope, a substantial incidence of appropriate device discharges was observed, particularly in patients with inducible SMVT and LVEF ≤ 0.35. These findings support the notion that, in patients with LV dysfunction and inducible SMVT, ventricular tachyarrhythmias are likely to account for episodes of syncope or near‐syncope.
Influence of Epinephrine, Propranolol, and Atrial Pacing on Spatial Distribution of Recovery Time Measured by Body Surface Mapping in Congenital Long QT Syndrome
Authors: SHIMIZU WATARU , KAMAKURA SHIRO , KURITA TAKASHI , SUYAMA KAZUHIRO , AIHARA NAOHIKO , SHIMOMURA KATSURO
Published: April 2007

Recovery Time in Congenital LQTS. Introduction: Sympathetic stimulation plays an important role in the genesis of QT(U) prolongation and ventricular arrhythmias in congenital long QT syndrome (LQTS). Permanent pacemaker as well as β blockers are reported to be effective in the management of this syndrome. The purpose of this study was to examine influence of epinephrine (α and β‐adrenergic stimulation), propranolol (β blocker), and atrial pacing on the spatial distribution of repolarization using body surface recovery time (RT) in congenital LQTS.

Methods and Results: Body surface mapping was recorded in 16 patients with congenital LQTS and 20 control patients before and after epinephrine infusion (0.1 μg/kg per min), oral propranolol (1 to 2 mg/kg per day), addition of epinephrine during oral propranolol, atrial pacing at a cycle length of 600 or 750 msec, and addition of epinephrine during atrial pacing. The RT, that is, the interval between the QRS onset and the maximum dV/dt point in the ST‐T segment, was measured automatically by a computer from each of the 87 mapping leads, and the corrected RT (RTc) was calculated using Bazett's method. In patients with congenital LQTS, epinephrine markedly changed the T(U) wave morphology and spatial distribution of RT, especially the distribution of maximum RT of the left anterior chest and back, Epinephrine prolonged the maximum RTc and the minimum RTc in 87 leads and increased the RTc dispersion (difference between maximum and minimum RTc in each patient). Neither propranolol nor atrial pacing changed the T(U) wave morphology, spatial distribution of RT, or any RT, parameters at rest. Propranolol prevented the influences of epinephrine on the T(U) wave morphology, spatial distribution of RT, and Rc parameters, whereas atrial pacing did not. In control patients, marked changes of the T(U) wave morphology and RT, parameters were not recognized during the entire protocol.

Conclusions: Our results indicate that epinephrine markedly changes the spatial distribution of repolarization and increases the dispersion of repolarization, which probably are linked to arrhythmogenesis in congenital LQTS. The data suggest that propranolol but not atrial pacing are effective to suppress repolarization abnormalities during sympathetic stimulation.
Relation of the Atrial Input Sites to the Dual Atrioventricular Nodal Pathways:
Authors: TCHOU PATRICK J. , CHENG YUANNA N. , MOWREY KENT , EFIMOV IGOR R. , VAN WAGONER DAVID R. , MAZGALEV TODOR N.
Published: April 2007

Dual AV Nodal Pathways. Introduction: The usually accepted definition of the dual pathway electrophysiology requires the presence of conduction curves with a discontinuity (“Jump”). However, AV nodal reentrant tachycardia has been ohserved in patients with “smooth” conduction curves, whereas discontinuity of the conduction curve does not guarantee induction of stable reentry. We hypothesize that the duality of AV nodal conduction can be revealed by careful choice of stimulation sites during the generation of AV nodal conduction curves.

Methods and Results: In 21 rabbit heart atrial‐AV nodal preparations, programmed electrical stimulation with S1‐S2‐S3 pacing protocol was applied eitber posteriorly at the crista terminalis input site (CrT) or anteriorly at the lower interatrial septum input site (IAS), or (in 8 preparations with surgically divided input sites) at both. We found tbat in intact preparations with “smooth” conduction curves, pacing at long coupling intervals produced shorter AV nodal conductiim times from the IAS (56 ± 9.8 msec vs 69 ± I 0.1 msec; P < 0.01). At short coupling intervals, in contrast, shorter conduction times were obtained from the CrT (173 ± 21.8 msec vs 188 ± 22.8 msec; P < 0.01). This resulted in a characteristic crossing of the superimposed IAS and CrT conduction curves. After division of the inputs, the IAS site had rapid conduction to the His bundle but a longer refractory period, whereas the CrT site bad long conduction times and sborter refractory periods. Wavefronts entering the AV node from these two inputs can summate, resulting in improved conduction.

Conclusion: Pacing protocols designed to accentuate tbe asymmetry between tbe AV nodal inputs can belp to reveal tbe functional difference between tbe dual pathways and thus to better assess the properties of AV nodal conduction.
Electrophysiologic Features of Torsades de Pointes:
Authors: ZABEL MARKUS , HOHNLOSER STEFAN H. , BEHRENS STEEFEN , LI YI‐GANG , WOOSLEY RAYMOND L. , FRANZ MICHAEL R.
Published: April 2007

Torsades de Pointes in the Isolated Rabbit Heart. Introduction: The exact electrophysiologic mechanism of torsades de pointes (TdP) is under intense investigation. No isolated animal heart model of this particular arrhythmia exists.

Methods and Results: In isolated rabbit hearts, TdP was induced by means of bradyeardia in the presence of a high concentration of d‐sotalol (10−4 M) and shortly after lowering the concentration of potassium and magnesium in the perfusate. Multiple simultaneous epicardial and endocardial monophasic action potentials (MAPs) and volume‐conducted 12‐lead ECGs were recorded. d‐Sotalol prolonged repolarization and increased dispersion of ventricular repolarization compared to baseline recordings. With the onset of low potassium and magnesium concentrations, repolarization was further prolonged and dispersion of repolarization was further increased followed by the occurrence of early afterdepolariZations (EADs) in the majority of MAP recordings, i.e., at both endocardial and epicardial locations of both ventricles, upon increase of EAD amplitude, triggered arrhythmias with TdP of up to 42 heats ensued in 10 of 11 hearts studied. MAP duration at 90% repolarization (APD90), dispersion of APD90, and the incidence of EADs as well as dispersion of the QT interval and T wave area were significantly higher in heats triggering higemini, couplets, or runs of TdP.

Conclusion: TdP observed in this new isolated heart model was associated with markedly increased dispersion of ventricular repolarization and the occurrence of EADs in multiple locations of the heart. TdP is initiated when the amplitude of an EAD reaches threshold for initiation of the first beat of an episode.
Antiarrhythmic Drug Therapy in the Management of Atrial Fibrillation
Authors: GANZ LEONARD I. , ANTMAN ELLIOTT M.
Published: April 2007

Antiarrhythmic Drugs for AF. Antiarrhythmic drugs have been used for the acute conversion of atrial fibrillation to sinus rhythm, as well as for the long‐term maintenance of sinus rhythm. In recent years, concerns regarding antiarrhythmic drug efficacy as well as safety have prompted a re‐examination of the indications for antiarrhythmic therapy in patients with atrial fibrillation. This review will focus on the safety and efficacy of antiarrhythmic therapy in the acute and chronic management of patients with atrial fibrillation.
Newer Clinical Applications of Pacing
Authors: GLIKSON MICHAEL , HAYES DAVID L. , NISHIMURA RICK A.
Published: April 2007

Newer Clinical Applications of Pacing. For many years, the indications for permanent cardiac pacing consisted primarily of AV block and sinus node dysfunction. In recent years, the indications for pacing have expanded considerably. This article details recent advances in the application of permanent pacing and the use of permanent pacing for patients with hypertrophic cardiomyopathy, dilated cardiomyopathy, prevention of atrial fibrillation, and pacing in the long QT syndrome. Pacing is now an accepted therapeutic modality in hypertrophic cardiomyopathy and has rapidly gained acceptance in the United States, although there are still many unknowns about selection of patients and long‐term benefits. Even less is known about pacing for dilated cardiomyopathy. Certain patients do respond with definite subjective improvement and improved quality of life, although there are no data to date to suggest improved longevity. Pacing for long QT syndrome is now a well‐accepted indication for this relatively small subset of patients. Pacing for the prevention of atrial fibrillation is still in the very early stages of development. Multiple methods have been tried with the current method of choice being dual site atrial pacing. However, it is too early to predict the long‐term success of this modality.
Differential Effects of D‐Sotalol, Quinidine, and Amiodarone on Dispersion of Ventricular Repolarization in the Isolated Rabbit Heart
Authors: ZABEL MARKUS , HOHNLOSER STEFAN H. , BEHRENS STEEFEN , WOOSLEY RAYMOND L. , FRANZ MICHAEL R.
Published: April 2007

Drug Effects on Dispersion of Repolarization. Introduction: increased dispersion of ventricular repolarization has been suggested as a cause of proarrhythmic effects of Class IA or III antiarrhythmic drugs, such as d‐sotalol, quinidine, and amiodarone.

Methods and Results: The influence of d‐sotalol, quinidine, and amiodarone on the dispersion of monophasic action potential (MAP) durations was studied in 55 isolated Langendorff‐perfused rabbit hearts at different pacing cycle lengths (CLs). MAP dnration measured at 90% repolarization (APD90) was determined from 6 to 8 endocardial and epicardial MAP recordings with dispersion of ventricular repolarization defined as the range of APD90. The protocol was repeated 60 minutes after initiation of a perfusate containing increasing concentrations of d‐sotalol (n = 12, 10−6 M, 10−5 M, and 5 × 10−5 M) and quinidine (n = 8, 10−6 M and 10−5 M). Seventeen rabbits were fed with an aqueous solution of amiodarone (50 mg/kg per day over 4 weeks). The data of these experiments (n = 17) were compared with a series of 18 untreated control rabbits. Dispersion of ventricular repolarization was unchanged with the low concentration of d‐sotalol (10−6 M) but was increased—particularly at long CLs—with higher d‐sotalol concentrations. With both concentrations of quinidine, dispersion of ventricular repolarization was increased in a rate‐independent manner. Amiodarone did not affect dispersion of ventricular repolarization.

Conclusions: Rate‐dependent and concentration‐dependent increases in dispersion of ventricular repolarization by d‐sotalol and quinidine in this isolated rabbit heart model may help explain their proarrhythmic effects while the absence of an increase in dispersion of ventricular repolarization with amiodarone correlates with its clinically observed lower incidence of proarrhythmia.
Chronic Amiodarone Reduces Transmural Dispersion of Repolarization in the Canine Heart
Authors: SICOURI SERGE , MORO SANDRA , LITOVSKY SILVIO , ELIZARI MARCELO V. , ANTZELEVITCH CHARLES
Published: April 2007

Amiodarone Reduces Transmural Dispersion. Introduction: Amiodarone is a potent antiarrhythmic agent used in the management of both atrial and ventricular arrhythmias. In addition to its β‐blocking properties, amiodarone is known lo block the sodium, potassium, and calcium channels in the heart. Its complex electropharmacology notwithstanding, the reasons for the high efficacy of the drug remain unclear. Also not well understood is the basis for the low incidence of proarrhythmia seen with amiodarone relative to other agents with Class III actions. The present study was designed to examine the effects of chronic amiodarone in epicardial, endocardial, and M cells of the canine left ventricle.

Methods and Results: We used standard microelectrode techniques to record transmembrane activity from endocardial, epicardial, mid‐myocardial, and transmural strips isolated from the canine left ventricle. Tissues were obtained from mongrel dogs receiving amiodarone orally (30 to 40 mg/kg per day) for 30 to 45 days or from untreated controls. Chronic amiodarone produced a greater prolongation of action potential duration in epicardium and endwardium, but less of an increase, or even a decrease at slow rates, in the M region, thereby reducing transmural dispersion of repolarization. In addition, chronic amiodarone therapy suppressed the ability of the Ikr, blocker, d‐sotalol, to induce a marked dispersion of repolarization or early afterdepolarization activity.

Conclusion: Our data demonstrate for the first time a direct effect of chronic amiodarone treatment to differentially alter the cellular electrophysiology of ventricular myocardium so as to produce an important decrease in transmural dispersion of repolarization, especially under conditions in which dispersion is exaggerated. These results may contribute to our understanding of the effectiveness of amiodarone in the treatment of life‐threatening arrhythmias as well as to our understanding of the low incidence of proarrhythmia attending therapy with chronic amiodarone in comparison with other Class III agents.
Atypical Atrioventricular Nodal Reentry Tachycardia with Atrioventricular Block Mimicking Atrial Tachycardia:
Authors: TANIGUCHI YASUHIRO , YEH SAN‐JOU , WEN MING‐SHIEN , WANG CHUN‐CHIEH , WU DELON
Published: April 2007

AVNRT Mimicking Atrial Tachycardia, Introduction: Fast‐intermediate form AV nodal reentry tachycardia (AVNRT) sometimes may mimic atrial tachycardia or atrial flutter and render the diagnosis difficult when the tachycardia rate is fast and AV block occurs during tachycardia.

Methods and Results: A 45‐year‐old woman with paroxysmal supraventricular tachycardia was referred to this institution. Initially, the tachycardia was thought to be an atrial tachycardia because of: (1) a short cycle length of the tachycardia with 2:1 and Wenckebach AV block; (2) a difference in the atrial activation sequence during tachycardia and during ventricular pacing; and (3) failure of burst ventricular pacing to affect the atrial rate and the atrial activation sequence during tachycardia. An accurate diagnosis of fast‐intermediate form AVNRT was subsequently made based on the finding that the tachycardia was induced following delivery of a third ventricular extrastimulus, which showed a sequence of V‐A‐H and a change on atrial activation sequence of the induced beat. Successful radiofrequency ablation was achieved only after accurate diagnosis of the tachycardia was made.

Conclusion: Fast‐intermediate form AVNRT sometimes may masquerade as atrial tachycardia. Accurate diagnosis is mandatory for successful ablation therapy.
Conduction Velocity in the Tricuspid Valve‐Inferior Vena Cava Isthmus is Slower in Patients With Type I Atrial Flutter Compared to Those Without a History of Atrial Flutter
Authors: FELD GREGORY K. , MOLLERUS MICHAEL , BIRGERSDOTTER‐GREEN ULRIKA , FUJIMURA OSAMU , BAHNSON TRISTRAM D. , BOYCE KER , RAHME MARC
Published: April 2007

Slower Conduction in the TV‐IVC Isthmus. Introduction: In human type I atrial flutter, the electrophysiologic substrate is unclear. In order to determine if slow conduction is mechanistically important, we evaluated conduction velocity in the tricuspid valve‐inferior vena cava (TV‐IVC) isthmus, right atriai free wall, and interatrial septum in patients with and without a history of atrial flutter undergoing electrophysiologic study.

Methods and Results: Nine patients with (group 1) and nine without a history of type I atrial flutter (group 2) were studied. Conduction time (msec) in the right atrial free wall. TV‐IVC isthmus (bidirectional), and interatrial septum was measured during pacing in sinus rhythm at cycle lengths of 600, 500, 400, and 300 msec from the low lateral right atrium and coronary sinus ostium. Conduction velocity (cm/sec) was calculated by dividing the distance between pacing electrodes and sensing electrodes (cm) by the conduction time (sec). Conduction velocity was slower in the TV‐IVC isthmus in group 1 (range 37 ± 8 to 42 ± 8 cm/sec) versus group 2 (range 50 ± 8 to 55 ± 9 msec) at all pacing cycle lengths (P < 0.05). However, conduction velocity was not different in the right atrial free wall or interatrial septum between groups 1 and 2. Conduction velocity was also slower in the TV‐IVC isthmus than in the right atrial free wall and interatrial septum in group 1 patients, at all pacing cycle lengths (P < 0.05). Atrial flutter cycle length correlated with total atrial conduction time (r ≥ 0.832, P < 0.05).

Conclusion: Slow conduction in the TV‐IVC isthmus may be mechanistically important for the development of human type I atrial flutter.
Clinical Recurrences After Successful Accessory Pathway Ablation:
Authors: SCHLÜTER MICHAEL , CAPPATO RICCARDO , OUYANG FEIFAN , ANTZ MATTHIAS , SCHLÜTER CATARINA A. , KUCK KARL‐HEINZ
Published: April 2007

Dormant Accessory Pathways. Introduction: Recurrence of clinical symptoms after radiofrequency catheter ablation of an accessory atrioventricular pathway (AP) may be due to the late manifestation of an additional AP that was not detected during the initial ablation session. It was the purpose of this study to elucidate the phenomenon of these “dormant” APs.

Methods and Results: Of 1280 consecutive patients who underwent radiofrequency catheter ablation of an AP, 54 patients (4.2 %) developed clinical symptoms postablation, necessitating a repeat ablation session. Recurrence of conduction over the AP targeted al the initial ablation session was found in 45 patients, whereas in the other 9 patients (0.7%) the manifestation of a previously unnoticed AP had caused symptom recurrence. Retrospective analysis of the data from these patients’ ablation sessions revealed that the late manifesting AP was ablated at a site clearly different from that of the initially targeted AP, and that the manifestation of conduction over a previously “dormant” AP occurred significantly later than the recovery of a presumably ablated AP. Seven (78%) of the 9 “dormant” APs were concealed, and none exhibited decremental conduction properties.

Conclusion: The incidence of clinical recurrences mediated by the late manifestation of conduction over a previously “dormant” AP is low. The lack of an anatomic vicinity of these predominantly concealed APs with the initially targeted AP and the lack of evidence for their presence during the initial ablation session suggest intermittent conduction as the most likely explanation for their late manifestation.
Low‐Energy Impedance‐Compensating Biphasic Waveforms Terminate Ventricular Fibrillation at High Rates in Victims of Out‐of‐Hospital Cardiac Arrest
Authors: POOLE JEANNE E. , WHITE ROGER D. , KANZ KARL‐GEORG , HENGSTENBERG FRIEDERIKE , JARRARD G. TRUETT , ROBINSON JACK C. , SANTANA VALERIE , McKENAS DAVID K. , RICH NATHAN , ROSAS STEVEN , MERRITT SALLY , MAGNOTTO LUKE , GALLAGHER JOHN V. , GLINER BRADFORD E. , JORGENSON DAWN B. , MORGAN CARLTON B. , DILLON STEPHEN M. , KRONMAL RICHARD A. , BARDY GUST H. ,   for the LIFE INVESTIGATORS
Published: April 2007

Biphasic Waveform Defibrillation. Introduction: New automatic external defibrillators (AEDs), which are smaller, lighter, easier to use, and less costly make the goal of widespread AED deployment and early defibrillation for out‐of‐hospital cardiac arrest feasible. The objective of this study was to observe the performance of a low‐energy impedance‐compensating biphasic waveform in the out‐of‐hospital setting on 100 consecutive victims of sudden cardiac arrest.

Methods and Results: AEDs incorporating a 150‐J impedance‐compensating biphasic waveform were used by 12 EMS systems. Data were obtained from the AED PC card reporting system. Defibrillation was defined as conversion to an organized rhythm or to asystole. Endpoints included: defibrillation efficacy for ventricular fibrillation (VE); restoration of an organized rhythm at the time of patient transfer to an advanced life support (ALS) team or to the emergency department (ED); and time from AED power‐on to first defibrillation. The AED correctly identified 44 of 100 patients presenting in VE as requiring a shock (100% sensitivity) and 56 of 100 patients not in VF as not requiring a shock (100% specificity). The time from 911 call to first shock delivery averaged 8.1 ± 3.0 minutes. A single 150‐J biphasic shock defibrillated the initial VE episode in 39 of 44 (89%) patients. The average time from power‐on to first defibrillation was 25 ± 17 seconds. At patient transfer to ALS or ED care, an organized rhythm was present in 34 of 44 (77%) patients presenting with VF. Asystole was present in 7 (16%) and VE in 3 (7%).

Conclusions: Low‐energy impedance‐compensating biphasic waveforms terminate long‐duration VE at high rates in out‐of‐hospital cardiac arrest. Use of this waveform allows AED device characteristics consistent with widespread AED deployment and early defibrillation.
The Effects of Ventricular Fibrillation Duration and a Preceding Unsuccessful Shock on the Probability of Defibrillation Success Using Biphasic Waveforms in Pigs
Authors: WINDECKER STEPHAN , KAY G. NEAL , H BRUCE , WALCOTT GREGORY P. , SMITH WILLIAM M. , IDEKER RAYMOND E.
Published: April 2007

Influence of VF Duration on Defibrillation Efficacy. introduction: While the defibrillation threshold has been reported to increase with ventricular fibrillation (VF) duration for monophasic waveforms, the effect of VF duration for biphasic waveforms is unknown.

Methods and Results: The ED 50 requirements (the 50% probability of defibrillation success) for an endocardial lead system, which included a subcutaneous array, were determined by logistic regression using a recursive up‐down algorithm for a biphasic waveform ((6/6 msec). The study was performed in two parts, each with eight pigs. In part 1, ED 50 was compared for shocks delivered after 10 seconds of VF and for shocks delivered after 20 seconds of VF following a failed first shock at 10 seconds. Energy at ED 50 decreased from 6.5 ± 0.9, J for shocks delivered after 10 seconds of VF to 4.9 ± 0.8, J (P < 0.01) for shocks delivered after 20 seconds. To determine if improved second shock efficacy was a result of preconditioning by the failed first shock or a function of VF duration, part 2 of the study compared defibrillation efficacy between shocks delivered after 10 seconds of VF with shocks delivered after 20 seconds of VF with and without a failed first shock at 10 seconds. Mean energy at ED 50 decreased from 10.1 ± 2.4, J for shocks delivered after 10 seconds of VF to 7.9 ± 2.4 J (P < 0.01) and 7.5 ± 3.2 J (P < 0.01) for shocks delivered after 20 seconds of VF with and without a failed first shock, respectively. The mean energy at KD 50 for shocks delivered after 20 seconds of VK with and without a failed first shock was not significantly different (P = 0.53). A strong linear correlation for energy at ED 50 was found between shocks delivered after 10 seconds of VF and shocks delivered after 20 seconds of VF following a failed first shock (r = 0.95, P < 0.01).

Conclusion: (1) As opposed to monophasic shocks, ED 50 is significantly lower for biphasic shocks delivered after 20 seconds of VF compared with shocks delivered after 10 seconds of VF in pigs. (2) An unsuccessful biphasic shock in pigs does not affect the defibrillation efficacy for a subsequent shock. (3) ED 50 for a biphasic shock delivered after 20 seconds of VK is linearly related to ED 50 for a shock delivered after 10 seconds of VK.