bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of a Novel Missense Mutation in the Pore of HERG in a Patient with Long QT Syndrome
Authors: YOSHIDA HIDETADA , HORIE MINORU , OTANI HIDEO , TAKANO MAKOTO , TSUJI KEIKO , KUBOTA TOMOYUKI , FUKUNAMI MASATAKE , SASAYAMA SHIGETAKE
Published: April 2007

HERG Mutation and Long QT Syndrome. introduction: A new strategy to elucidate the molecular mechanisms underlying the long QT syndrome (LQTS) is now available with genetic mutational analyses and characterization of ion channel mutations.

Methods and Results: In a 26‐year‐old woman with LQTS, we identified a novel missense mutation in the pore of HERG by using polymerase chain reaction/single‐strand conformation polymorphism (PCR/SSCF) and sequencing of her genomic DNA. The mutation resulted in an amino acid substitution of a positively charged lysine for a highly conserved uncharged asparagine at codon 629 (N629K). Whole cell, patch clamp studies were conducted in COS7 cells by transfecting with wild‐type (WT) and/or the mutant N629K HERG. The WT HERG produced an IKr‐like, E‐4031‐sensitive conductance with an inward rectification. In contrast, the cells transfected with the N629K HERG did not display any time‐dependent current. Cotransfection of WT and N629K HERG (at a ratio of 1:1) produced a significantly smaller conductance when compared with WT HERG (WT 59.9 ± 7.3 pA/pF [n = 22] vs WT+N629K 5.5 ± 2.3 pA/pF [n = 11]; P < 0.01), but did not alter K+ ion selectivity and tail current‐voltage dependence. Because aprindine hydrochloride was effective in preventing ventricular tachycardias, we also tested the effect of the drug on WT HERG (IKr) and KvLQT1/KCNE1 (IKs) currents expressed in COS7.

Conclusion: Functional analyses of a novel missense mutation in the pore of HERG suggest that the mutation causes marked reduction of IKr via a dominant negative effect.
Electrophysiology of Postinfarction Ventricular Tachycardia:
Authors: RICHARDSON ALLISON W. , CALLANS DAVID J. , JOSEPHSON MARK E.
Published: April 2007

Point of View. Sustained monomorphic ventricular tachycardia (VT) is a paradigm of a stable reentrant rhythm. The hallmark of stable reentry is the presence of an excitable gap, which in reentrant VT composes 15% to 45% of the tachycardia cycle length. Resetting allows definition of the extent and pattern of the excitable gap. Site‐specific resetting responses suggest that the VT circuit has both functionally and anatomically derived characteristics. Entrainment provides information regarding the effects of overdrive pacing on properties of the tissue composing the circuit rather than on properties of the tachycardia itself. These data help us to understand the mechanisms of pharmacologic agents and to direct ablation of reentrant VT.
Determinants of Efficacy of Atrial Pacing in Preventing Atrial Fibrillation Recurrences
Authors: STABILE GIUSEPPE , SENATORE GAETANO , De SIMONE ANTONIO , TURCO PIETRO , COLTORTI FERNANDO , NOCERINO PASQUALE , VITALE DINO FRANCO , CHIARIELLO MASSIMO
Published: April 2007

Atrial Pacing in Atrial Fibrillation. Introduction: Several studies have shown that single or dual site atrial pacing is effective in reducing he frequency of recurrent atrial fibrillation (AF) in selected patients. However, it is still unclear what the best predictors are of long‐term efficacy of atrial pacing.

Methods and Results: Forty‐seven patients with paroxysmal AF requiring demand pacing underwent electrophysiologic study and dual chamber pacemaker implant. After 4 months of follow‐up, patients were divided into two groups according to the presence (group 1) or absence (group 2) of symptomatic AF recurrences. Atrial pacing markedly reduced AF recurrences in all patients. Twenty‐four patients were free of arrhythmia. The basal state conduction times (CTs) and the incremental conduction times (ICTs), during programmed electric stimulation between the high right atrium (HRA) and the coronary sinus ostium (CSos) but not between the HRA and the His‐bundle region, were significantly longer in group 1. There was no statistical difference in the effective refractory period (ERP) recorded at the HRA, the low right atrium (LRA), and the CSs between the two groups, whereas the differences between the greatest and least recorded ERPs measured from the HRA, LRA, and CSos (δERP) were significantly greater in group 1 patients. Two parameters were selected by discriminant multivariate analysis, namely δCTos (ICT‐CT between HRA and CSos and δERP. The first bad a greater relative importance in predicting AF recurrence (r2= 0.33 and r2= O.1, respectively).

Conclusion: Single site atrial pacing is effective in reducing AF recurrences, with decreasing efficacy in patients with greater right atrial conduction delay and wider refractoriness dispersion.
Clinical Value of the Postpacing Interval for Mapping of Ventricular Tachycardia in Patients with Prior Myocardial Infarction
Authors: BOGUN FRANK , KNIGHT BRADLEY , GOYAL RAJIVA , STRICKBERGER S. ADAM , HOHNLOSER STEFAN J. , MORADY FRED
Published: April 2007

Postpacing Interval. Introduction: The postpacing interval (PPI) has been used to discriminate bystander sites from critical sites within a ventricular tachycardia (VT) reentry circuit, with a PPI that is similar to the VT cycle length (CL) being indicative of a site within the reentry circuit. The purpose of this study was to assess the clinical value of the PPI for identifying effective target sites for ablation of VT at sites of concealed entrainment in patients with prior myocardial infarction.

Methods and Results: In 24 patients with coronary artery disease and a past history of myocardial infarction, 36 VTs with a mean CL of 483 ± 80 msec (± SD) were mapped and targeted for radiofrequency (RF) ablation. The only criterion used to select target sites for ablation was concealed entrainment. In a post hoc analysis, the PPI was measured at 47ineffective and 26 effective ablation sites. The mean PPI‐VTCL difference at the 26 effective sites(114 ± 137 msec) did not differ significantly from the mean at the 47 ineffective sites (177 ± 161msec; P = 0.1). The sensitivity of a PPI‐VTCL difference ≤ 30 msec for identifying an effective ablation site was 46%, the specificity 64%, the positive predictive value 41%, and the negative predictive value 68%.

Conclusion: The PPI‐VTCL difference is not useful for discriminating between sites of concealed entrainment that are within or outside of a VT reentry circuit in patients with prior infarction. Therefore, in patients with prior infarction, the PPI is not clinically useful for identifying sites of concealed entrainment at which RF ablation should or should not beat tempted.
Junctional Tachycardia During Radiofrequency A blation of the Slow Pathway in Patients with AV Nodal Reentrant Tachycardia: Effects of autonomic Blockade
Authors: CHEN MIEN‐CHENG , GUO G. BIH‐FANG
Published: April 2007

Junctional Tachycardia of AV Nodal Reentrant Tachycardia. Introduction: Theautonomic nervous system richly innervates the peri‐AV nodal region and may be activated during radiofrequency (RF) ablation for AV nodal reentrant tachycardia, resulting in the generation of junctional tachycardia. The purpose of this prospective study was to determine the role of the autonomic nervous system in the genesis of junctional tachycardia.

Methods and Results: We compared the characteristics of junctional tachycardia in patients with (n = 10) and without (n = 10) autonomic blockade undergoing RF ablation for AV nodal reentrant tachycardia. Intravenous administration of atropine (0.04 mg/kg) and propranolol (0.2 mg/kg) were used to block the autonomic nervous system. There were no differences in clinical variables and baseline electrophysiologic characteristics between the two groups except for slightly longer effective refractory periods of the fast pathway and of the atrium in the autonomic blockade group. The autonomic blockade shortened the baseline sinus cycle length and effective refractory period of the ventricle only but not other electrophysioiogic characteristics of the AV node. The junctional tachycardia was observed during ablation in each patient, but its occurrence and cycle length, as well as numbers of consecutive junctional beats, were not altered by the autonomic blockade.

Conclusion: Our results indicate that the muscarinic and beta‐adrenergic components of the autonomic nervous system play no role in the genesis of junctional tachycardia.
Microwave Ablation of Myocardial Tissue
Authors: THOMAS STUART P. , CLOUT RAY , DEERY CATHERINE , MOHAN ANANDA S. , ROSS DAVID L.
Published: April 2007

Microwave Ablation of Myocardial Tissue. Introduction: The biophysical properties of microwave electromagnetic radiation suggest that it may be an alternative to radiofrequency (RF) energy for ablation of arrhythmias resistant to treatment using RF ablation.

Methods and Results: The aim of this study was to characterize lesions produced using simple element designs in a blood super fused ovine tissue model to simulate endocardial ablation. The effect of tissue bath flow, duration of microwave exposure, and changes in forward power on lesion size were examined using a modified monopole element. Lesion size increased with increasing duration of exposure and increasing forward power (P ≤ 0.05). Lesion depth was 0.7 ± (1.7 mm after 30 seconds and n.5 ± L9 mm after 360 seconds. Lesion depths at 61. 71, and 80 W were 6.4 ± 3.7, 8.9 ±±2.0, and 11.9 ± 1.2 mm, respectively. Altering flow within the bath from 3 to 5 L/min did not significantly change lesion size.

Conclusion: Simple element designs can be used to produce a range of lesions from very small sizes to lesions that are transmural in the ventricle. The temperature half‐time for microwave ablation is far greater than that of RF ablation. Like RF lesions, the lesions produced by microwave ablation have greater width than depth. Deep penetration of lesions into the ventricular myocardium can (only be achieved with these elements by producing lesions of perhaps unnecessarily large volume.
Two‐to‐One AV Block Associated with the Congenital Long QT Syndrome
Authors: PRUVOT ETIENNE , De TORRENTE ANTOINE , De FERRARI GAETANO M. , SCHWARTZ PETER J. , GOY JEAN‐JACQUES
Published: April 2007

2:1 AV Block in LQTS. Introduction Conduction abnormalities associated with long QT syndrome (LQTS) have been reported as “pseudo 2:1 AV block” due to sinus intervals shorter than ventricular refractoriness.

Method and Results: We report the electrophysiologic characteristics of a patient suffering from congenital LQTS with episodes of true 2:1 AV block. Induction of 2:1 infra‐Hisian blocks and return to 1:1 conduction were observed using single atrial and ventricular extrastimuli. The block was located in the Purkinje network but not in the myocardium.

Conclusion: The His‐Purkinje system of our LQTS patient displayed dynamic properties with a strong increase in refractoriness for short‐long sequences and a decrease for long‐short sequences that triggered intermittent 2:1 AV blocks.
Spontaneous Inversion of an Implanted Defibrillator
Authors: Rosenbaum David S. , DRABEK CAROLE A. , QUAN KARA J. , ROSENBAUM DAVID S.
Published: April 2007

A 67‐year‐old man with ischemic cardiomyopathy received an implantable defibrillator for ventricular fibrillation 3 years ago. He now presents with weight loss and an inability to interrogate or establish any telemetric communication with his defibrillator. An abdominal radiograph was obtained (right) that, when compared to a film obtained 5 months earlier (left) illustrated a significant change in the position of the device. Inspection of the manufacturer radiographic
Sodium Pentobarbital Reduces Transmural Dispersion of Repolarization and Prevents Torsades de Pointes in Models of Acquired and Congenital Long QT Syndrome
Authors: SHIMIZU WATARU , McMAHON BRANDON , ANTZELEVITCH CHARLES
Published: April 2007

Electrophysiologic Effects of Pentobarbital. Introduction: Sodium pentobarbital is widely used for anesthesia in experimental studies as well as in clinics, and it is known to prevent the development of torsades dc pointes (TdP) in in vivo models of the long QT syndrome (LQTS).

Methods and Results: This study examines the effects of pentobarbital on transmural dispersion of repolarization (TDR) and induction of TdP in arterially perfused canine left ventricular wedge preparations in which transmembrane action potentials were simultaneously recorded from epicardial, M, and endocardial regions using floating glass microelectrodes together with a transmural ECG. d‐Sotalol and ATX‐II were used to mimic the LQr2 and LQT3 forms of congenital LQTS. Both d‐sotalol (100 μmol/L, n = 6) and ATX‐II (20 nmol/L., n = 6) preferentially prolonged the action potential duration (APD90) of the M cell, thus increasing in the QT interval and TDR, and leading to the development of spontaneous and stimulation‐induced TdP. In the absence and presence of d‐sotalol, pentobarbital (10, 20, and 50 μg/mL) prolonged the APD90 of epicardial and endocardial cells, and, to a lesser extent, that of the M cell, thus prolonging the QT interval but reducing TDR. In the ATX‐II model, the effects of pentobarbital on the QT interval and APD90 were biphasic: 10 μg/mL pentobarbital further prolonged APD90 of epicardial and endocardial cells more than that of the M cell; 20 to 50 μg/mL pentobarbital abbreviated the APD90 of epicardial and endocardial cells less than that of the M cell, thus abbreviating the QT internal and markedly reducing TDR. Twenty to 50 μg/mL pentobarbital totally suppressed spontaneous as well as stimulation‐induced TdP in both models.

Conclusion: Our data indicate that pentobarbital reduces TDR in control and under conditions of congenital and acquired LQTS, and suggest that this mechanism may contribute to the ability of the anesthetic to prevent the development of spontaneous as well as stimulation‐induced TdP under conditions mimicking LQT2, LQT3, and acquired (drug‐induced) forms of the LQTS. The data also serve to illustrate that there are circumstances under which QT prolongation may not be arrhythmogenic.
ECG of the “Newborn” Mouse (Mus Domesticus) with Specific Reference to Comparative AV Transmission
Authors: van der TWEEL L. HENK , STRACKEE JAN , STOKHOF ARNOLD A. , WASSENAAR CLAES , MEIJLER FRITS L.
Published: April 2007

Comparative AV Transmission. Introduction: The objective of this study was to record the ECG of the smallest living mammal to extend the domain of data for comparative A V nodal electrophysiologic purposes. These data are needed to establish the relationship between the PR interval and heart size in mammalian species of all sizes.

Methods and Results: In recently horn mice (age 1.5 to 8 weeks) weighing between 2.5 and 10 g and with estimated heart weights between 15 and 60 mg, ECGs, using bipolar limb leads, were recorded during general anesthesia. The PR interval, representing AV transmission time was about 40 msec, which is quite long for hearts of this size. On the basis of detailed analysis of the data, we postulate the presence of a fixed delay or discontinuous propagation in the AV node not only in newborn mice, hut in mammals of all sizes.

Conclusion: A V transmission times obtained in mammals (including humans) cannot be explained on the basis of generally accepted, classic AV conduction theories. The acceptance of the presence of a fixed delay in the A V node may ultimately be of value to better understand A V node function during sinus rhythm and supraventricular arrhythmias.
Dynamic Changes in Electrogram Morphology at Functional Lines of Block in Reentrant Circuits During Ventricular Tachycardia in the Infarcted Canine Heart
Authors: CIACCIO EDWARD J. , SCHEINMAN MELVIN M. , FRIDMAN VITALIY , SCHMITT HEIKO , COROMILAS JAMES , WIT ANDREW L.
Published: April 2007

Localization of Reentrant Circuits Using ATM. Introduction: Fractionated, low‐amplitude or long‐duration electrograms have limited specificity for locating reentrant circuits causing ventricular tachycardia (VT). In this study a new method is described, adaptive template matching (ATM), based on the quantification of beat‐to‐beat changes in electrograms, for locating functional reentrant circuits that are relatively stable and cause monomorphic VT.

Methods and Results: Monomorphic VTs were induced in 4‐day‐old infarcted canine hearts by programmed stimulation and reentrant circuits mapped in the epicardial border zone with a 196 or 312 bipolar electrode array. For ATM analysis, a template electrogram from each electrode, during an early cycle, was matched with all subsequent (input) electrograms at the same site by weighting the inputs of amplitude, duration, average baseline, and phase lag. The mean square error (MSE) between template and input was the criterion used to adapt the weights, and was also a measure of changes in electrogram shape that occur from cycle to cycle. The variance of each of the weighting parameters at all electrode sites were plotted on a representation of the electrode array, and the location of the functional lines of block bounding the central common pathway of reentrant circuits with figure‐of‐eight characteristics, overlaid on the ATM map. Peaks of high variance were found to be coincident with functional lines of block during all tachycardia episodes.

Conclusion: Specific beat‐to‐beat changes in electrograms occur at functional lines of block in reentrant circuits that can be quantified by ATM analysis, suggesting that these regions might be located without activation mapping. The method might be useful to guide ablation catheter position.
Long‐Term (Subacute) Potassium Treatment in Congenital HERG‐Related Long QT Syndrome (LQTS2)
Authors: TAN HANNO L. , ALINGS MARCO , VAN OLDEN RUDOLF W. , WILDE ARTHUR A.M.
Published: April 2007

Potassium Treatment in LQTS2. Introduction: Congenital long QT syndrome (LQTS) is subdivided according to the underlying gene defect. In LQTS2, an aberrant HERG gene that encodes the potassium channel IKr leads to insufficient IKr activity and delayed repolarization, causing ECG abnormalities and torsades de pointes (TdP). Increasing serum potassium levels by potassium infusion normalizes the ECG in LQTS2 because IKr activity varies with serum potassium levels.

Methods and Results: In an LQTS2 patient who presented with TdP, we attempted to achieve a long‐term (subacute) elevation of serum potassium by increased potassium intake and potassium‐sparing drugs. However, due to renal potassium homeostasis, it was impossible to achieve a long‐lasting rise of serum potassium above 4.0 mmol/L.

Conclusion: Although raising serum potassium reverses the ECG abnormalities in LQTS2, a long‐lasting rise of serum potassium is only partially achievable because in the presence of normal renal function, potassium homeostasis limits the amount of serum potassium increase.
Capture Window in Human Atrial Fibrillation
Authors: CAPUCCI ALESSANDRO , RAVELLI FLAVIA , NOLLO GIANDOMENICO , MONTENERO ANNIBALE S. , BIEFL MAURO , VILLANI GIOVANNI Q.
Published: April 2007

Capture Window in Human AF. Introduction: Local capture of atrial fibrillation (AF) was shown in animal experiments for a wide range of pacing rates, thus demonstrating the existence of an excitable gap. The aim of this study was to assess the existence of an excitable gap in human AF by studying the mechanism of local control and acceleration of AF over a wide range of pacing rates and by evaluating the time window of capture.

Methods and Results: Recording and stimulation of electrical activity in the right atrium during AF was performed by a monophasic action potential (MAP) contact electrode catheter in 17 patients with lone AF during electrophysiologic study. Stimulation was started at pacing intervals close to the mean AF interval, and the time window of capture was estimated by lengthening or shortening the pacing interval until capture was lost. Pacing intervals shorter than the minimum cycle length for capture were also tested. Beat‐to‐beat measurements of AF intervals during pacing were performed. Atrial MAP signal showed rapid irregular activity with an average AF interval of 151.3 ± 16.1 msec and SD of 21.3 ± 5.2 msec. Rapid pacing with a cycle length slightly shorter or longer than the mean AF interval resulted in local capture of AF. The width of time window of capture ranged from 22 to 36 msec, with a mean value of 28.8 ± 4.9 msec. The average minimum pacing interval of stable capture was 129.2 ± 19.5 msec, while the maximum was 158.1 ± 18.7 msec, corresponding to 85% and 104% of mean AF cycle length, respectively. Pacing too rapidly resulted in a transient acceleration of AF, with an average shortening of fibrillation interval from 149.8 ± 16.6 to 123.2 ± 15.1 msec (P < 0.01).

Conclusion: Local capture is feasible during AF in humans over a wide range of pacing rates, indicating the possibility of regional control of the fibrillatory process. This result demonstrates the presence of an excitable gap during AF in human atria.
Discrete Systolic Potentials During Ventricular Tachycardia in Patients with Prior Myocardial Infarction
Authors: BOGUN FRANK , KNIGHT BRADLEY , GOYAL RAJIVA , MICHAUD GREGORY F. , STRICKBERGER S. ADAM , HOHNLOSER STEFAN H. , MORADY FRED
Published: April 2007

Systolic Potentials, introduction: Isolated diastolic potentials have been found to be helpful in identifying critical sites for ablation of ventricular tachycardia (VT) in patients with coronary artery disease. However, discrete potentials that occur during systole have not been previously described. The purpose of this study was to determine the significance of discrete systolic potentials during VT in patients with coronary artery disease.

Methods and Results: Twenty‐seven patients with a mean age of 66 ± 12 years (± standard deviation) who bad coronary artery disease underwent radiofrequency catheter ablation of 42 VTs that had a mean cycle length of 486 ± 78 msec. The only criterion used to select target sites for ablation was concealed entrainment, which was present at 92 sites. Thirty‐five of the 42 VTs (83%) were successfully ablated. A discrete systolic potential was recorded during 7 of the 42 VTs (17%). In all cases, the interval between the discrete systolic potential and the next QRS complex was equal to the stimulus‐QRS interval during concealed entrainment. At all seven sites where a discrete systolic potential was recorded, delivery of radiofrequency energy resulted in successful ablation of the VT.

Conclusion: Discrete systolic potentials may be present in patients with coronary artery disease in approximately 17% of VTs in which there is concealed entrainment. If the interval between the discrete systolic potential and the next QRS complex matches the stimulus‐QRS interval during concealed entrainment, delivery of radiofrequency energy is likely to result in successful ablation of the VT.
Congestive Heart Failure Induced by Recipient Atrial Tachycardia Conducted to the Donor Atrium after Orthotopic Heart Transplantation
Authors: GASPARINI MAURIZIO , MANTICA MASSIMO , LUNATI MAURIZIO , ANDREUZZI BRUNO , TURCO PIETRO , PELLEGRINI ALESSANDRO
Published: April 2007

Graft Failure and Recipient Atrial Tachycardia. We describe the case of a 30‐year‐old female patient who developed an interatrial tachycardia from the recipient to the donor atrium associated with signs of congestive heart failure 5 years after orthotopic heart transplantation. The patient underwent catheter mapping followed by successful radiofrequency (RF) ablation at the site of the presumed electrical connection between the recipient and the donor atria, through the interatrial surgical suture line, with stable recovery of sinus rhythm and disappearance of signs of left ventricular dysfunction. RF catheter ablation is confirmed to be feasible and safe in the treatment of heart transplant patients even in the presence of rare forms of arrhythmias, thus offering a cure for tachycardia to these patients.
Myocardial Hypothermia
Authors: HALE SHARON L. , KLONER ROBERT A.
Published: April 2007

Cardioprotection by Mild Hypothermia. The importance of temperature in the development of necrosis after myocardial ischemia in the beating heart is becoming apparent. Recent studies have shown that the proportion of the ischemic risk zone that becomes necrotic is directly correlated with temperature. This fact suggests the potential therapeutic benefits of reducing myocardial temperature after coronary artery occlusion. We have shown in a number of experimental protocols in the rabbit model of myocardial infarction that topical regional hypothermia reduces infarct size even when instituted after coronary artery occlusion. The reduction in myocardial temperature required to obtain this benefit is modest (30°C to 34°C). Topical regional hypothermia allows targeted cooling of a zone of the heart. Myocardial cooling can also be achieved by perfusing the pericardial sac with a chilled fluid by using a closed‐circuit catheter system that does not cause cardiac tamponade. This technique also protects myocardium during ischemia. Myocardial hypothermia might be a useful technique to limit ischemic damage during infarction or as adjunctive therapy during minimally invasive cardiac surgery.
Atrial Sensing and AV Synchrony in Single Lead VDD Pacemakers: A Prospective Comparison to DDD Devices with Bipolar Atrial Leads
Authors: WIEGAND UWE K.H. , BODE FRANK , SCHNEIDER REGINA , TAUBERT GUNNAR , BRANDES AXEL , PETERS WERNER , KATUS HUGO A. , POTRATZ JURGEN
Published: April 2007

Atrial Sensing and AV Synchrony in VDD and DDD Devices, Introduction: Single lead VDD pacing has offered an alternative to DDD systems in patients with isolated AV block. Up to now, however, the relative performance of these pacemaker systems was not systematically compared.

Methods and Results: Three hundred sixty patients who received either a VDD pacemaker (n = 180) or a DDD device (n = 180) with a bipolar atrial lead were investigated prospectively for a mean period of 30 ± 13 months. Pacemaker function was analyzed by telemetry. Holter monitoring, and exercise ECG. Time of implantation and fluoroscopy was significantly lower with VDD devices (44.3 ± 5.1 min vs 74.4 ± 13.5 min and 4.6 ± 2.5 min vs 10.3 ± 5.6 min in DDD pacemakers, respectively). Intermittent atrial undersensing occurred in 23.3% of patients with a VDD pacemaker and in 9.4% with DDD devices (NS). The incidence of atrial tachyarrhythmias did not differ between the VDD (6.7%) and the DDD group (6.1%). Sinns node dysfunction developed in 1.9% of patients, but the vast majority (85.7%) of patients were asymptomatic. There was a tendency for a higher rate of operative revisions in the DDD group (6.1% vs 3.3% in VDD pacemakers, P = 0.15). Cumulative maintenance of AV‐synchronized pacing mode was 94.9% in patients with VDD pacemakers and 92.1% with DDD devices (NS).

Conclusion: With the benefit of a simpler implant procedure, long‐term outcome of single lead VDD pacing is equivalent to DDD pacing in patients with AV block and preoperative normal sinus node function.
Wavelength and Conduction Inhomogeneity in Each Atrium in Patients with Isolated Mitral Valve Disease and Atrial Fibrillation
Authors: NITTA TAKASHI , IMURA HAJIME , BESSHO RYUZOU , HOSAKA HIROKI , YAMAUCHl SHIGEO , TANAKA SHIGEO
Published: April 2007

AF in Mitral Valve Disease. Introduction: Patients with mitral valve disease frequently have atrial fibrillation (AF), and the left atrium is presumed to be the primary atrium that develops AF. However, it is still not clear whether the electrophysiologic abnormalities responsible for AF are confined to the left atrium in this subset of patients.

Methods and Results: To examine the AF vulnerability of each atrium, we measured the wavelength and in homogeneity of the conduction at the lateral right atrium, lateral left atrium, and Bachmann's bundle after defibrillation of AF in seven patients undergoing the maze procedure and mitral valve surgery for AF and isolated mitral valve disease, respectively (AF group). The data were compared with five coronary surgery patients in sinus rhythm (SR group). The wavelength in the AF group was significantly shorter (P < 0.05) than in the SR group not only at the lateral left atrium (225 ± 62 vs 285 ± 36 mm) but also at the lateral right atrium (214 ± 54 vs 254 ± 34 mm). The variation coefficient of the local maximum activation phase difference in the AF group (1.9 ± 0.8 at the right atrium, 2.1 ± 0.8 at the lateral left atrium, and 2.0 ± 0.6 at Bachmann's bundle) was significantly greater (P < 0.05) than in the SR group at all atrial regions.

Conclusion: AF vulnerability was not confined to the left atrium immediately after defibrillation in AF patients with isolated mitral valve disease. Electrical remodeling resulting from perpetuation of AF, pathological changes extending to the right atrium, geometric changes caused by the atrial interactions occurring across the interatrial septum, or a combination of these may explain the results.
A Role for the Renin‐Angiotensin System in the Evolution of Cardiac Memory
Authors: RICARD PHILIPPE , JR PETER DANTLO , COHEN IRA S. , BURKHOFE DANIEL , ROSEN MICHAEL R.
Published: April 2007

Angiotensin II and Cardiac Memory. Introduction: We studied the role of the cardiac renin‐angiotensin II system in the genesis of cardiac memory, in which T wave changes induced by ventricular pacing (VP) accumulate and persist during subsequent sinus rhythm.

Methods and Results: Anesthetized dogs were instrumented via a thoracotomy and three 20‐minute runs of VP were interspersed with periods of normal sinus rhythm sufficient to permit T wave recovery to 90% of control. Memory was quantified as the change (δ) in T wave vector angle showing accumulation over the three monitoring periods. In five control dogs T wave vector = ‐ 27 ± 49°, and this shifted by 104° (P < 0.05) over the three postpacing recovery periods. In seven dogs infused with the receptor blocker saralasin, five infused with the angiotensin‐converting enzyme inhibitor captopril, and four infused with the tissue protease inhibitor chymostatin, there were significant reductions in the incidence and the accumulation of memory. In four other experiments, we used isolated, blood‐perfused canine hearts to demonstrate that VP used to induce memory alters the contractile pattern of the left ventricle.

Conclusions: We propose that the alteration in myocardial stretch induced by pacing activates angiotensin II synthesis by cardiac cells. We propose, further that the endogenous cardiac renin‐angiotensin II system (blocked by saralasin, captopril and by chymostatin) is an important contributor to the induction of memory.
Catheter Mounted Coaxially Moveable Ablation Electrode for the Creation of Linear Transmural Endocardial Lesions
Authors: MORGAN JOHN MARK , ROBERTS PAUL RICHARD , ALLEN STUART , GALLAGHER PATRICK JOSEPH , GIBSON CHARLES , CUNNINGHAM ANDREW DAVID
Published: April 2007

Coaxially Moveable Ablation Catheter. Introduction: Use of a novel ablation catheter for the creation of linear transmural endocardial lesions, which uses a coaxially moving ablation electrode mounted on the terminal portion of a catheter shaft and able to move axially for a distance of up to 4 cm. is reported.

Methods and Results: The coaxially moving ablation electrode is moved by a sliding mechanism in the catheter handle. The distal portion of the catheter shaft is steerable. Bipolar or unipolar electrograms can be recorded from electrodes on the catheter tip and the coaxially moving ablation. Radiofrequency (RF) current is delivered to the coaxially moving ablation electrode with thermocouple temperature control. This ablation catheter was evaluated in five (30 to 65 kg) anesthetized pigs and introduced via the venous/arterial systems into the right and left atrium (1 lesion) (using the retrograde aortic approach). The catheter was maneuvered to bring the slide range into apposition with atrial endocardium. The coaxially moving ablation electrode was deployed to the terminal portion of the catheter's slide range and then withdrawn in 2‐mm steps. RF current was delivered to the coaxially moving ablation electrode at each point (maximum temperature 70° C), Postmortem examination of eight endocardial linear lesions (2.2 to 4.1 cm length) was made 1 to 3 hours after creation. Histopathologic examination confirmed transmural myocyte necrosis along the length of the lesion, that included the trabeculated right atrium.

Conclusion: We conclude that a catheter using a moveable electrode creates continuous linear transmural lesions and could find clinical application in the therapy of a variety of reentry tachycardia mechanisms.
Radiofrequency Ablation of a Concealed Nodoventricular Mahaim Fiber Guided by a Discrete Potential
Authors: HLUCHY JAN , SCHLEGELMILCH PETER , SCHICKEL STEFAN , JÖRGER URS , JURKOVICOVA OLGA , SABIN GEORG V.
Published: April 2007

Concealed Nodoventricular Mahaim Fiber. Introduction: We present the case of a 17‐year‐old woman who underwent an electrophysiological study and radiofrequency (RF) ablation of supraventricular tachycardia refractory to medical treatment. Two right‐sided, concealed, nondecremental atrioventricular accessory pathways (AV‐APs) involved in ortho‐dromic circus movement tachycardias were identified. After RF ablation of both AV‐APs, evidence of bidirectional dual AV nodal conduction was demonstrated and regular narrow complex tachycardia was induced.

Methods and Results: During the tachycardia, retrograde slow and fast AV nodal pathway conduction with second‐degree ventriculoatrial (VA) block and VA dissociation were observed. During the tachycardia with second‐degree VA block, ventricular extrastimuli elicited during His‐bundle refractoriness advanced the next His potential or terminated the tachycardia. Mapping the right atrial mid‐septal region, a distinct high‐frequency activation P potential was recorded in a discrete area, two thirds of the way from the His bundle toward the os of the coronary sinus. Detailed electrophysiologic testing with the recordahle P potential demonstrated that the tachycardia utilized a concealed nodoventricular AP arising from the proximal slow AV nodal pathway.

Conclusion: The tachycardia with slow 1:1 VA conduction could be reset by ventricular extrastimuli elicited during His‐bundle refractoriness advancing the subsequent activation P potential and atrial activation. RF ablation guided by recording of the activation P potential resulted in elimination of both the slow AV nodal pathway and the nodoventricular connection with preservation of the normal AV conduction system.
Thromboembolic Complications of Cardiac Radiofrequency Catheter Ablation
Authors: ZHOU LI , KEANE DAVID , REED GUY , RUSKIN JEREMY
Published: April 2007

Thromboembolic Complications of Cardiac RF Catheter Ablation. Introduction: Radiofrequency catheter ablation (RFCA) has become established as an effective therapy for the treatment of many cardiac tachyarrhythmias. The principle limitation of conventional RFCA continues to be the risk of thromboembolism. This risk is of particular concern for the ongoing development of the catheter maze procedure for the treatment of atrial fibrillation, which currently involves the creation of extensive linear lesions in the left atrium.

Methods and Results: A Medline search of the literature over the last ten years was performed. Focused review of the reported thromboembolic complications of RFCA indicates an overall incidence of 0.6%. However, the risk is increased when ablation is performed in the left heart (1.8% to 2%) and for ventricular tachycardia (2.8%). It is of concern that intravenous heparin and the use of temperature feedback to control radiofrequency current do not eliminate the risk of thromboembolic events.

Conclusion: The thromboembolic complications of RFCA are not eliminated by the treatment of intravenous herapin and mode of temperature control during ablation. Potential approaches to further reduce the risk of thromboembolism include the adjunctive administration of specific inhibitors of platelet activation and aggregation, intraprocedural intracardiac echocardiography, irrigated radiofrequency ablation, and cryoablation catheter systems.
Noninvasive Diagnosis in Patients with Undocumented Tachycardias:
Authors: TEBBENJOHANNS JÜRGEN , NIEHAUS MICHAEL , KORTE THOMAS , DREXLER HELMUT
Published: April 2007

Noninvasive Diagnosis in Patients with Undocumented Tachycardias. Introduction: Patients with symptoms suggestive of paroxysmal supraventricular tachycardia (PSVT) but no tachycardia documentation often undergo diagnostic electrophysiologic study. In dual AV node physiology with AV node reentrant tachycardia (AVNRT), the anterograde fast pathway is more sensitive than the slow pathway to the effects of adenosine. The purpose of the study was to test the hypothesis that adenosine can be used as a bedside test for the diagnosis of dual AV node physiology and hence for AVNRT.

Methods and Results: During electrophysiologic study, 37 patients without prior documentation hut symptoms indicative for PSVT received incremental dosages of adenosine during sinus rhythm until second‐degree or greater AV block was observed. Suggestive signs of dual AV node physiology on the surface ECG (sudden jump of PQ interval ≥ 50 msec) were found in 13 (76%) of 17 patients with inducible AVNRT but in only 1 (5%) of the remaining patients (P < 0.01). In the AVNRT group, the maximal increase of the PQ interval between two beats was greater (88 ± 45 msec) than in the remaining 20 patients (17 ± 11 msec) (P < 0.01).

Conclusion: Careful evaluation of surface ECG during administration of adenosine helps to identify patients prone to AVNRT. The adenosine test is a valuable noninvasive adjunct in patients with undocumented palpitations suggestive of PSVT
Radiofrequency Catheter Ablation of Frequent Monomorphic Ventricular Ectopic Activity
Authors: SEIDL KARLHEINZ , SCHUMACHER BURGHARD , HAUER BERND , JUNG WERNER , DRÖGEMÜLLER AXEL , SENGES JOCHEN , LÜDERITZ BERNDT
Published: April 2007

Ablation of Ventricular Ectopic Activity. Introduction: Frequent ventricular ectopic beats can result in severe symptoms and may even be incapacitating in some patients. Although radiofrequency catheter ablation is an effective and safe therapy for drug refractory idiopathic ventricular tachycardia, it has not been widely used in ventricular ectopy. The purpose of this study was: (1) to assess the potential role of catheter ablation in eliminating monomorphic ventricular ectopy in symptomatic patients regarding feasibility and safety and (2) to determine the usefulness of various mapping strategies.

Methods and Results: Forty‐one patients with symptomatic ventricular ectopic activity (right ventricular origin in 23 patients, left ventricular origin in 18 patients) were enrolled. The mean frequency of ventricular ectopic beats was 1512 ± 583/hour documented by Holter ECG monitoring. These patients had previously been unable to tolerate or had been unsuccessfully treated with a mean of 3 ± 1 antiarrhythmic agents. The site of origin was mapped using earliest endocardial activation times, unipolar electrograms and pace mapping. Radiofrequency ablation was successful in 34 (83%) of 41 patients. Multivariate logistic regression analysis revealed pace mapping as the only independent predictor for a successful ablation site (P < 0.01). After a follow‐up of 3 months, the overall success rate was 71%. The mean frequency of ventricular ectopic heats after successful ablation was 12 ± 10 ventricular premature beat/hour. Conclusion: Radiofrequency catheter ablation is an effective and safe treatment for frequent symptomatic drug refractory monomorphic ventricular ectopic activity. Pace mapping predicts best successful ablation of ventricular ectopic beats.
A Four‐Shock Bayesian Up‐Down Estimator of the 80% Effective Defibrillation Dose
Authors: MALKIN ROBERT A. , HERRE JOHN M. , McGOWEN LAUREN , TENZER MARTHA M. , ONUFER JOHN R. , STAMATO NICHOLAS J. , WOOD MARK , BERNSTEIN ROBERT C.
Published: April 2007

Bayesian Estimation of the ED80.Introduction: New defibrillation techniques are often compared to standard approaches using the defibrillation threshold. However, inference from thresholding data necessitates extrapolation from reactions to relatively ineffective shocks, an error prone procedure requiring large sample sizes for hypothesis testing and large safety margins for defibrillator implantation. In contrast, this article presents a clinically validated statistical model of a minimum error, four‐shock defibrillation testing protocol for estimating the 80% effective defibrillation strength for a given patient (ED80).

Methods and Results: A Bayesian statistical model was constructed assuming that the defibrillation dose‐response curve is sigmoidal, and the ED80 is between 150 and 750 V. The model was used to design a minimum predicted error testing protocol and estimates. To prospectively validate the testing protocol and estimates, 170 patients received voltage‐programmed biphasic testing. Four fibrillation episodes were induced and terminated in each patient according to the Bayesian up‐down protocol. In addition, a validation attempt was made at the estimated ED80 rounded up to the nearest 50 V. In order to estimate the safety margin, in 136 patients, a defibrillation attempt was made at the rounded ED80 + 100 V. Of the 170 attempts at the rounded ED80, 143 (84%) attempts terminated fibrillation. Of the 136 attempts at the rounded ED80 + 100 V, 133 (98%) were effective.

Conclusions: The four‐shock Bayesian up‐down protocol is the first clinical protocol to accurately predict an ED80 voltage. A 100 V increment above the ED80 provides an adequate safety margin. This simple and accurate method for estimating a highly effective defibrillation dose may be a valuable tool for population‐based clinical hypothesis testing, as well as defibrillator implantation.
The Autonomic Control of the Transmural Dispersion of Ventricular Repolarization in Anesthetized Dogs
Authors: TAKEI MANABU , SASAKI YASUYUKI , YONEZAWA TAKANORI , LAKHE MANOJ , ARUGA MASAKAZU , KIYOSAWA KENDO
Published: April 2007

Autonomic Effects of M Region. Introduction: The initiation of ventricular arrhythmias is in part associated with autonomic nervous tone. We investigated the effects of sympathetic and parasympathetic stimulation on the monophasic action potentials (MAPs) of the epicardium (EPi), mid‐myocardial (M) region, and endocardium (Endo) in vivo.

Methods and Results: In 12 mongrel open chest anesthetized dogs, both sides of the cervical vagus nerves and stellate ganglia were crushed with a tight ligature. Right atrial pacing at 600 msec cycle length was begun after the sinus nodal area had been crushed. MAPs from the M region were measured by two needle electrodes that were supported by a W‐shaped plastic frame. The epicardial, M region, and endocardial MAP durations at 90% repolarization (MAPD90) were 287 ± 7, 315 ± 7, and 290 ± 8 msec, respectively. The MAPD90 from M cells was longer than that from Epi or Endo. Sympathetic stimulation shortened MAPD90 more in the M region (53 ± 4 msec) than that in the Epi (27 ± 3 msec) or Endo (26 ± 4 msec). The transmural dispersion of repolarization during sympathetic stimulation was shorter than that of the control. Parasympathetic stimulation did not significantly affect any of the MAPD90 values. Simultaneous sympathetic and parasympathetic stimulation produced changes not significantly to those produced by sympathetic stimulation alone.

Conclusion: Our results suggest that sympathetic activity can reduce transmural dispersion of repolarization under autonomic control in the canine heart under baseline conditions.
Junctional Communication Between Isolated Pairs of Canine Atrial Cells is Mediated by Homogeneous and Heterogeneous Gap Junction Channels
Authors: ELENES SERGIO , RUBART MICHAEL , MORENO ALONSO P.
Published: April 2007

Heterogeneous Cardiac Gap Junction Channels. Introduction: The expression of multiple connexins (Cxs) in the canine right atria raises the possibility that heterogeneous gap junction channels might he formed.

Methods and Results: We compared the unitary conductance (γj) of gap junction channels between isolated canine atrial cell pairs with those of homogeneous cardiac gap junction channels expressed in other systems. After partial uncoupling with halothane (2 mmol/L), the γj calculations for atrial isolated cardiocytes ranged from 30 to 220 pS and their distribution in event histograms was spread over the entire range, with a small peak at ∼100 pS. This distribution deviates from the discrete peaks calculated from γj of homogeneous channels. All–points histograms of junctional current traces revealed distinct open–state levels. Some of these are related to the main open state of connexin43 (Cx43) (∼100 pS), observed between canine ventricular cells, or connexin40 (Cx40) (∼215 pS) observed between transfected N2A cells under similar recording conditions. Intermediate values for γj were not observed in recordings from ventricular cells, which express mostly Cx43, nor in those from N2A cells expressing Cx40, but were observed consistently between atrial cells. Because they were measured as first openings from the nonconductance state, these intermediate values most likely represent main conductance states of heterogeneous channels rather than subconductance states of homogeneous channels.

Conclusion: This suggests that regulation of cell–to–cell coupling in the heart depends not only on posttranslational modulation of preexisting Cxs, but also on the intracellular assembly mechanisms, and the way individual Cxs interact with others within a connexon and/or with other connexons from adjacent cells.
Review: Clinical Aspects of Vascular Remodeling
Authors: HERITY NIALL A. , WARD MICHAEL R. , LO SIDNEY , YEUNG ALAN C.
Published: April 2007

Clinical Aspects of Vascular Remodeling. Vascular remodeling represents a spectrum of structural changes whereby the vascular wall responds to changes in its hemodynamic environment. Such changes may be classified as vessel enlargement (outward remodeling), diminution (inward remodeling), alternatively as adaptive (compensatory, appropriate to the hemodynamic stimulus), or maladaptive (dysfunctional, inappropriate). The direction and scale of remodeling are coordinated by endothelial production of growth factors, proteases, and cellular adhesion molecules in response to sensed changes in blood flow. In early atherosclerosis, outward remodeling preserves lumen size. Although protective in the long‐term, the matrix degradation involved in this process may predispose atherosclerotic plaques to rupture, hence increasing the risks of acute coronary syndromes. Inward remodeling also occurs in advanced atherosclerotic lesions, whereby the vessel shrinks rather than enlarging, exacerbating rather than ameliorating stenosis. In transplant coronary artery disease, early inward remodeling may he a more important component of vessel stenosis than intimal thickening, while inappropriate inward remodeling appears to he as least as important as excessive intimal growth in the development of restenosis after angioplasty. Increased awareness of vascular remodeling, and in particular its malaptive forms, may provide new therapeutic insights for the future.