bluuebunny/crossref_metadata_2025 huggingface dataset:
The Controversial M Cell
Authors: ANYUKHOVSKY EVGENY P. , SOSUNOV EUGENE A. , GAINULLIN RAVIL Z. , ROSEN MICHAEL R.
Published: April 2007

The Controversial M Cell. A recent publication by us bas been interpreted by some as arguing against the existence and importance of M cells. We suppose this is the reason we have been asked to write this “controversy.” Regrettably for the controversy, neither our work nor we deny the existence of M cells. Rather, we have confirmed, conceivably ad nauseum, that M cells do exist and contribute importantly to the expression of electrical activity in the intact myocardium. What controversy there is relates to (1) whether there is an inhomogeneous transmural gradient for ventricular repolarization in normal hearts, and (2) why the electrophysiologic properties of different myocardial sites differ so markedly at the level of the isolated tissue and single cell and yet become so much more homogenous in the intact ventricle. These issues are addressed on the following pages.
An Overview of Arrhythmias and Antarrhythmic Approaches
Authors: ZIPES DOUGLAS P.
Published: April 2007

An Overview of Arrhythmias and Antiarrhythmic Approaches. Although treatment of cardiac arrhythmias has been revolutionized in the past decade, patients with atrial fibrillation (AF) still represent a major challenge. With the graying of the population, AF is increasing in prevalence and is responsible for significant morbidity, mortality, and health care expenditures. Drug therapy will he required for the majority of patients with this disorder. Patients with ventricular tachyarrhythmias represent the other major challenge to the cardiac electrophysiologist. The use of implantable cardioverter‐defibrillators (ICDs) has reduced the sudden death mortality to 1 % or less per year in patients at risk of dying from a ventricular tachyarrhythmia. Unfortunately, high‐risk patients who receive an ICD are only a small proportion of the patients who die suddenly each year. Considering the number of at‐risk patients, it is likely that drug therapy will remain the mainstay of treatment of patients with ventricular tachyarrhythmias. Therefore, the major challenge is to recognize patients at risk and treat them with antiarrhythmic drugs to prevent sudden cardiac death. Consequently, it has become clear that we have come to a crossroad with regard to antiarrhythmic drugs. Our knowledge of the molecular biology of cardiac ion channels, electrophysiology, and emerging antiarrhythmic drugs provides us an opportunity to create new pharmacologic stratagems.
The Molecular and Ionic Specificity of Antiarrhythmic Drug Actions
Authors: NATTEL STANLEY
Published: April 2007

The Molecular and Ionic Specificity of Antiarrhythmic Drug Actions. Virtually all clinical antiarrhythmic agents act by reducing ion channel conductance, with sodium (Na+), potassium (K+), and calcium (Ca++) channels the primary targets. Na+channel blockers increase the risk of ischemic ventricular fibrillation and are relatively contraindicated in the presence of active coronary heart disease. Ca++channel blockers suppress A V nodal conduction and are used to terminate reentrant supraventricular arrhythmias and control the ventricular response to atrial fibrillation. K+channels constitute the most diverse group of cardiac ion channels. They are the primary targets of Class III antiarrhythmic drugs, the category of such agents presently undergoing the most active development. The rapid delayed rectifier, Ikr, plays a key role in repolarization of all cardiac tissues and is the most common (and often only) target of action potential‐prolonging drugs. Unfortunately, because of the ubiquity of IKrreverse use‐dependent action potential prolongation that results from blocking it, lKrblockers are likely to cause torsades de pointes ventricular proarrhythmia. Kkschannel blockers, such as amiodarone and azimilide, that affect the slow delayed rectifier Iksas well as Iksappear to produce a more desirable rate‐dependent profile of Class III action. Recently, much has been learned about the molecular basis of K+channels based on their role in the congenital long QT syndrome. The availability of molecular clones that encode many of the channels in the human heart allows for the rapid screening of many potential new drugs, making possible the development of “designer” antiarrhythmic drugs with specific profiles of channel‐blocking selectivity.
Automatic and Efficient R Wave Discrimination in the Right Atrium Using a Two‐State Hidden Markov Model
Authors: SUN WEIMIN , COMBS WILLIAM , PANKEN ERIC , FOTUHI PARWIS , STANGL KARL , BAUMANN GERT , THERES HEINZ
Published: April 2007

Far‐Field R Wave Detection Using an HMM. Introduction: Discrimination of far‐field R waves from atrial events in atrial electrograms (EGMs) is problematic in present implantable pacing systems. Adjustments of atrial refractory periods and sensitivity settings are the only options, and they will not provide optimal performance in many patients. The reliable detection or rejection of R waves in atrial EGMs would avoid problems of atrial undersensing or oversensing, thus benefiting DOD patients by providing more reliable and specific atrial arrhythmia detection. In addition, detection of far‐field R waves could allow a measurement of AV conduction time in AAI and aid in discrimination of supraventricular tachyarrhythmia from ventricular tachyarrhythmia.

Methods and Results: Both atrial and ventricular unipolar EGMs were collected from 25 patients undergoing pacemaker implant or replacement. An average of 141 seconds of intrinsic or VVI paced EGMs was recorded and post analyzed. A new two‐state hidden Markov model (HMM) was developed specifically for far‐field R wave and P wave discrimination in the atrium. The recorded patients' EGMs were analyzed using this model, and the sensitivity and positive predictivity of far‐field R wave detection were evaluated. The collected atrial EGMs were visually examined and marked as the control for verification of the detection analysis. Far‐field R wave detection using this model had an overall sensitivity of 94%± 9.4% and a positive predictivity of 98.3%± 4.4%; and the far‐field R wave rejection using the same model had a sensitivity and a positive predictivity of 98.8%± 3.8% and 99.1%± 1.7%, respectively.

Conclusion: Far‐field R wave detection in the right atrium by the two‐state HMM is reliable and accurate, and can significantly improve atrial arrhythmia management for patients.
Intracardiac Echocardiography to Guide Transseptal Left Heart Catheterization for Radiofrequency Catheter Ablation
Authors: DAOUD EMILE G. , KALBFLETSCH STEVEN J. , HUMMEL JOHN D.
Published: April 2007

Transseptal Catheterization. Introduction: The purpose of this study was to asess the feasibility and safety of intracardiac echocardiography to guide transseptal puncture for radiofrequency catheter ablation.

Methods and Results: Transcatheter intracardiac echocardiography (9 MHz) was utilized to guide transseptal puncture in 53 patients undergoing radiofrequency catheter ablation. The anatomy and relationship of intra‐ and extracardiac structures were visualized with the ultrasound transducer positioned at the fossa ovalis. The tip of the transseptal dilator and tenting of the fossa ovalis and the left atrial wall were simultaneously visualized in a single ultrasound image in all patients. With maximum tenting of the fossa ovalis, the mean distance from the fossa to the left atrial wall was 11.9 ± 5.8 mm (range: 1.8 to 25.6 mm). In four patients (8%), the tented fossa ovalis abutted the left atrial wall and the transseptal dilator was redirected with ultrasound guidance. Puncture of the interatrial septum was achieved through the fossa ovalis in each patient and required a single attempt in 51 patients (96%). The mean number of punctures per patient was 1.1 ± 0.4. The mean time to perform transseptal catheterization was 18.2 ± 6.8 minutes. There were no complications.

Conclusion: Intracardiac echocardiography delineated the anatomy of intra‐ and extracardiac structures not identified with fluoroscopy and simplified correct positioning of the transseptal dilator, puncture of the fossa ovalis, and cannulation of the left atrium in a timely and uncomplicated fashion.
Relationship Between Shock Energy and Postdefibrillation Ventricular Arrhythmias in Patients with Implantable Defibrillators
Authors: ZIVIN ADAM , SOUZA JOSEPH , PELOSI FRANK , FLEMMING MATTHEW , KNIGHT BRADLEY P. , GOYAL RAJIVA , MORADY FRED , STRICKBERGER S. ADAM
Published: April 2007

Postdefibrillation Ventricular Arrhythmias. Background: The relationship between postdefibrillation ventricular arrhythmias and shock strength is poorly understood in patients with implantable defibrillators. The purpose of this study was to characterize the relationship between postdefibrillation ventricular arrhythmias and shock strength.

Methods and Results: Forty‐three patients with an implanted defibrillator underwent six separate inductions of ventricular fibrillation (VF) after a step‐down defibrillation energy requirement (7.3 ± 4.6 J) was determined. For each of the first three inductions of VF, the first two shocks were low energy and equal to approximately 75 % of the defibrillation energy requirement (5.4 ± 3.3 J), or to the defibrillation energy requirement plus 10 J (17.5 ± 4.3 J). After the first two shocks, subsequent shocks were programmed to the maximum available energy (29.0 ± 2.5 J). The alternate technique was used for the subsequent three inductions of VF. Post defibrillation ventricular arrhythmias were noted. Post defibrillation ventricular arrhythmias with a cycle length ≤ 300 msec were more frequent after a low‐energy shock (19%), than after a high‐energy shock (1.5 %; P = 0.005). Postdefibrillation ventricular arrhythmias with a cycle length > 300 msec were more frequent after a high‐energy shock (32%), than after a low‐energy shock (7.1%; P = 0.002). A relationship between the cycle length of the post defibrillation ventricular arrhythmias and the absolute defibrillation energy was observed (P < 0.001; r = 0.6), and ventricular arrhythmias with a cycle length > 300 msec were uncommon after shocks ≤ 10 J (P = 0.001). The characteristics of ventricular arrhythmias after maximum‐energy shocks were similar to those that occurred after high‐energy shocks.

Conclusions: Post defibrillation ventricular arrhythmias with a cycle length ≤ 300 msec are more common after shocks of strength associated with a low probability of successful defibrillation. Postdefibrillation ventricular arrhythmias with a cycle length of > 300 msec are more common after high‐ and maximum‐energy shocks, and are directly related to the absolute defibrillation energy.
Locating Ectopic Foci
Authors: HALL KEVIN , GLASS LEON
Published: April 2007

Locating Ectopic Foci. Introduction: Successful radiofrequency of an ectopic focus requires accurate localization of the region of enhanced automaticity. Present localization techniques require detailed electrical mapping that is time‐consuming and involves much trial and error. Here, we propose two new localization techniques which were used to locate a pacemaker in a computer simulation.

Methods and Results: We suggest that an ectopic focus can he located by measuring the activation sequence of three or more intracardiac electrodes subsequent to an ectopic depolarization. Furthermore, the resetting response of an ectopic pacemaker can be used to estimate the distance from the stimulation electrode to the ectopic focus. We derive simple geometric localization strategies based on these ideas and examine the sensitivity of the strategies with respect to measurement uncertainties and electrode arrangements. Our localization strategies were tested using a numerical simulation of a pacemaker in a sheet of excitable media described by modified FitzHugh‐Nagumo equations. The strategy based on electrode activation sequences located the pacemaker region in a homogeneous isotropic sheet after an average of 2.2 ± 0.8 iterates in 10 out of 10 trials starting from random initial catheter positions. In the case of an inhomogeneous anisotropic sheet, the pacemaker was located after an average of 4 ± 3 iterates in 9 out of 10 trials. The localization strategy based on resetting successfully found the pacemaker in a homogeneous isotropic sheet after an average of 1.2 ± 0.4 iterates in 5 out of 5 trials and localized the pacemaker in an inhomogeneous anisotropic sheet after an average of 1.4 ± 0.5 iterates in 5 out of 5 trials.

Conclusions: Simple geometric strategies can be used to locate an ectopic focus. Although our basic localization strategies are sensitive to the electrode arrangement and measurement uncertainties, we show that iteration of our techniques quickly locates the pacemaker.
Differential Effects of Adenosine on Focal and Macroreentrant Atrial Tachycardia
Authors: MARKOWITZ STEVEN M. , STEIN KENNETH M. , MITTAL SUNEET , SLOTWTNER DAVID J. , LERMAN BRUCE B.
Published: April 2007

Focal and Macroreentrant Atrial Tachycardia. Introduction: The effects of adenosine on atrial tachycardia (AT) remain controversial, and the mechanistic implications of adenosine termination have not been fully established. The purpose of this study was to elucidate the differential effects of adenosine on focal and macroreentrant AT and describe the characteristics of adenosine‐sensitive AT.

Methods and Results: Thirty patients received adenosine during AT. Tachycardia origins were identified as local or macroreentrant during invasive electrophysiologic studies. Responses to adenosine were analyzed and characterized as tachycardia termination, transient suppression, or no effect. Electrophysiologic studies demonstrated a focal origin of tachycardia in 17 patients. Adenosine terminated focal tachycardias in 14 patients (dose 7.3 ± 4.0 mg) and transiently suppressed the arrhythmias in three others (dose 10.0 ± 6.9 mg). A macroreentrant mechanism was demonstrated in 13 patients: adenosine terminated only one of these tachycardias and had no effect on the remaining 12 patients (dose 10.2 ± 2.9 mg). Four classes of adenosine‐sensitive AT were identified. Class I consisted of nine patients with tachycardia arising from the crista terminalis; these tachycardias also terminated with verapamil (4/4). Class II consisted of four patients with repetitive monomorphic AT arising from diverse sites in the right atrium; these either slowed or terminated in response to verapamil (2/2). Class III consisted of the three patients with transient suppression and demonstrated electropharmacologic characteristics consistent with an automatic mechanism, including insensitivity to verapamil (2/2). In the one patient with macroreentrant AT that was comprised of decremental atrial tissue, adenosine terminated tachycardia in a zone of decremental slow conduction (Class IV); this tachycardia slowed with verapamil.

Conclusions: Adenosine‐sensitive AT is usually focal in origin and arises cither from the region of the crista terminalis (inclusive of the sinus node) or from diverse atrial sites with an incessant nonsustained repetitive pattern. Although most forms of macroreentrant AT are insensitive to adenosine, rarely macroreentrant AT with zones of decremental slow conduction can demonstrate adenosine sensitivity.
The Activation of Platelet Function, Coagulation, and Fibrinolysis during Radiofrequency Catheter Ablation in Heparinized Patients
Authors: ANFINSEN OLE‐GUNNAR , GJESDAL KNUT , BROSSTAD FRANK , ORNING OTTO M. , AASS HALFDAN , KONGSGAARD ERIK , AMLIE JAN P.
Published: April 2007

Hemostatic Activation during RF Ablation. Introduction: Catheter ablation may be complicated by clinical thromboembolism in about 1% of patients.

Methods and Results: We studied the activation of coagulation (prothrombin fragment 1+2 [PFl+2]). platelets (β‐thromboglobulin [β‐TG])) and fibrinolysis (plasmin‐antiplasmin complexes [PAP) and D‐dimer) during radiofrequency (RF) ablation in 13 patients. They received heparin 100 U/kg intravenously alter the initial electrophysiologic study, prior to the delivery of RF current; thereafter 1,000 U/hour throughout the procedure. PF1+2 increased fourfold (P < 0.001) during the diagnostic study, but gradually declined to upper reference value during heparin administration. There was a strong correlation between procedure duration prior to heparin bolus (range 39 to 173 min); and (a) the maximal rise of PFl+2 (r = 0.83, P < 0.001) and (b) the increase of PFI+2 from baseline to end of the procedure (r = 0.74, P = 0.004). There was no correlation between postheparin changes of PFl+2 and (a) postheparin procedure duration (range 40 to 317 min), (b) number of RF pulses (range 1 to 16). or (c) RF current duration (range 46 to 687 sec). Plasma β‐TG concentration showed similar trends. Fibrinolytic activity increased moderately from baseline until heparin administration; then remained around the upper reference values. PAP at the end of procedure and D‐dimer at the time of heparin administration both correlated with preheparin procedure duration (r = 0.70, P = 0.007 and r = 0.69, P = 0.01. respectively). All parameters were normal the next morning.

Conclusion: Procedure duration prior to heparin administration, and not the delivery of RF current per se, determines activation of hemostasis and fibrinolysis during RF ablation.
Human Histopathologic Findings Following Radiofrequency Ablation of the Tricuspid‐Inferior Vena Cava Isthmus
Authors: LEONELLI FABIO M. , NATALE ANDREA , O'CONNOR WILLIAM
Published: April 2007

Human Histopathologic Findings Following RF Ablation. Radiofrequency (RF) ablation of the tricuspid valve‐inferior vena cava isthmus is now the first line of treatment in the management of typical atrial flutter. Successful ablation is associated with conduction block in this region, although the histopathologic changes following this procedure have never been reported. We describe the pathologic changes following RF ablation of this region in an explanted heart of a patient undergoing heart transplantation 4 months after successful atrial flutter ablation. The findings confirm the ability of RF ablation to create in the isthmus a chronic full thickness fibrosis, which represents the histopathologic counterpart of the conduction block demonstrated the end of procedure.
Distinctive RR Dynamics Preceding Two Modes of Onset of Spontaneous Sustained Ventricular Tachycardia
Authors: ANDERSON KELLEY P. , SHUSTERMAN VLADIMIR , AYSIN BENHUR , WEISS RAUL , BRODE SUSAN , GOTTIPATY VENKATESHWAR ,   for the ESVEM Investigators
Published: April 2007

RR Dynamics Before VT. Introduction: We hypothesized that autonomic activity preceding spontaneous sustained monomorphic ventricular tachycardia (VTsm) as assessed by heart rate (HR) and RR interval variability (RRV) differs between type 1 VTsm which is initiated by morphologically distinct, early cycle, possibly triggering premature ventricular complexes (PVCs) and type 2 VTsm in which the initial complex has a QRS waveform identical to subsequent complexes.

Methods and Results: Baseline Holter tapes (1,646) from a clinical trial were scanned for VTsm. QRS complexes of VTsm, were compared by two‐lead cross‐correlation to distinguish type 1 and type 2 VTsm, Frequency domain RRV index were estimated over 5 minutes, 15 minutes, and 24 hours. Type 1 and type 2 VTsm, were present in 15 (group 1) and 33 (group 2) of 48 patients, respectively. HR did not change in group 1 (88.4 ± 15.2 to 89.7 ± 13.0 beats/min, P = 0.89), but increased before the onset of VTsm in group 2 (74.3 ± 16.3 to 81.2 ± 18.0 beats/min, P < 0.001). RRV index were severely depressed in both groups. No RRV index changed significantly before the onset of type 1 VTsm, whereas significant changes occurred before type 2 VTsm from 24‐hour average to 30 minutes before VTsm in very low (very low‐frequency power [VLFP]: 6.62 ± 1.53 to 6.20 ± 2.07 In msec2, P = 0.036), low (low‐frequency power [LFP]: 5.61 ± 1.43 to 5.28 ± 1.59 in msec2, P = 0.004), normalized low (normalized low‐frequency power [LFPn]: ‐0.48 ± 0.58 to ‐0.55 ± 0.64 normalized units [nu], P = 0.05) and the ratio of LFP to high‐frequency power (HFP) (LPP/HFP: 4.20 ± 3.47 to 3.45 ± 2.53, P = 0.017). Declines in RRV index between 2 hours to the 30‐minute period before VTsm, occurred in group 2 but not group 1 in LFP (5.85 ± 1.42 to 5.28 ± 1.59 In msec, P = 0.043) and HFP (4.94 ± 5.14 to 3.46 ± 2.52 In msec2 P = 0.008), with a downward trend in LFP/HFP (4.94 ± 5.14 to 3.45 ± 2.53, P = 0.127) and LFPn (‐0.38 ± 0.36 to ‐0.55 ± 0.64, P = 0.15), while HFPn tended to rise (‐1.47 ± 0.65 to ‐1.27 ± 0.64, P = 0.15).

Conclusions: HR and RRV did not change before type 1 VTsm, suggesting that short‐term changes in autonomic activity were not essential to initiation of apparent PVC‐triggered VTsm. In contrast, RR interval dynamics before type 2 VTsm suggested that short‐term changes in neurohormonal activity contributed to arrhythmia initiation. Heterogeneities in arrhythmia onset may reflect distinct triggers and substrate properties that could provide a basis for effective therapeutic targets.
Discontinuous Propagation of the Cardiac Impulse and Arrhythmogenesis
Authors: Rudy Yoram , KLÉBER ANDRE G.
Published: April 2007

The complex discontinuous architecture of cardiac tissue induces a number of interactions between the cellular properties of the myocardium that affect impulse propagation:

1. Slow (< 10 cm/sec) conduction velocities in the myocardium can only be achieved by discontinuous conduction. In the more continuous type of conduction, as occurring during inhibition of INa, conduction block occurs at velocities of approximately 20 cm/sec.

2. If the discontinuity reaches a critical degree, Ica, L is needed to propagate the cardiac impulse. This situation may occur during cell‐to‐cell uncoupling and at sites of local tissue discontinuities.

3. The conduction phenomena occurring at tissue discontinuities, such as pivoting points, isthmus, and abrupt tissue expansions are markedly influenced by the underlying properties of the cellular network. Electrical uncoupling at the cellular level can reduce the effect of the discontinuities to produce conduction block and reverse unidirectional block to bidirectional conduction. By contrast, reduction of INa increases the probability of unidirectional block at such sites. Since activation of INa may become rate‐dependent at high rates and in depolarized tissue, this predicts an instability in activation patterns during a tachycardia.

Do the above considerations really predict arrhythmogensis? It is obvious that increasing the degree of structural discontinuity creates a substrate for reentrant arrhythmias. However, with the exception of the demonstration of spiral wave initation in vitro,5 no direct effects of tissue discontinuities on arrhythmia initiation have been demonstrated so far. Furthermore, pathologies associated with an increased degree of structural discontinuities, such as a hypertrophy and failure, also show an increased propensity to triggered arrhythmias, and initiation of ventricular tachcardias from small foci has been observed in whole hearts. These complexities make it difficult to extrapolate findings of experimental and theoretical work at the cellular level directly to whole hearts and human pathologies where several mechanisms for initiation and maintenance of tachycardias may coexist.
Role of the Input/Output Relation of Sinoatrial Myocytes in Cholinergic Modulation of Heart Rate Variability
Authors: ROCCHETTI MARCELLA , MALFATTO GABRIELLA , LOMBARDI FEDERICO , ZAZA ANTONIO
Published: April 2007

Input/Output Relation of the Sinoatrial Node. Introduction: Modulation of sinus rate may be viewed as the transduction of an input signal (receptor stimulation) into an output signal (cycle length [CL]) by the sinus node. This study analyzes the input/output (I/O) relation of sinoatrial pacemaking elements and tests its impact on cholinergic modulation of heart rate variability.

Methods and Results: Spontaneous activity of isolated rabbit sinoatrial myocytes was recorded by patch clamp techniques. CL and all the action potential parameters determining CL were automatically measured from >100 consecutive cycles. Acetylcholine (Ach, 5 to 50 nM) increased CL by decreasing diastolic depolarization rate (DDR) only. This was associated with a substantial increase in the coefficient of variation of CL and minor changes in the coefficient of variation of other parameters. A simple function relating CL to action potential parameters accurately described CL response to ACh (I/O relation). Numerical simulations based on this I/O relation showed that ACh‐induced depression of DDR might, by its own, increase CL variability.

Conclusion: Time‐domain measurements of CL variability may not necessarily reflect variability of the neural input to the sinoatrial node, but also may be affected by its tonic level. Properties of the I/O relation of sinoatrial myocytes may fully account for the dependency of CL variability on mean heart rate, previously described in humans. Any condition depressing DDR may enhance CL variability, independent of changes in the pattern of neural activity.
Focal Ablation of Chaotic Atrial Rhythm in an Infant with Cardiomyopathy
Authors: BEVILACQUA LAURA M. , RHEE EDWARD K. , EPSTEIN MICHAEL R. , TRIEDMAN JOHN K.
Published: April 2007

Ablation of Chaotic Atrial Rhythm. Chaotic atrial rhythm in infants has been defined similar to multifocal atrial tachycardia in adults, implying; a multifocal etiology. However, its ECG appearance resembles atrial fibrillation, which sometimes has a unifocal ectopic mechanism umenable to catheter ablation. Curative focal radiofrequency ablation was performed in a 4‐month‐old infant with chaotic atrial rhythm and dilated cardiomyopathy. Left ventricular function subsequently returned to normal. Reversibility of associated cardiomyopathy supports aggressive rhythm management of chaotic atrial rhythm. In this patient, the unifocal origin allows insight into the pathophysiology of the rhythm and demonstrates the potential utility of catheter ablation for refractory cases.
Respiratory Changes in Vasovagal Syncope
Authors: KURBAAN ARVINDER S. , ERICKSON MARK , PETERSEN MARK E.V. , FRANZEN ANN‐CHRISTINE , STACK ZARA , WILLIAMS TIMOTHY , SUTTON RICHARD
Published: April 2007

Respiratory Changes in Vasovagal Syncope. introduction: Respiratory changes accompany the cardiovascular changes during head‐up. tilt test‐induced vasovagal syncope.

Methods and Results: Using the 45‐minute 60° head‐up Westminster protocol, 29 patients were studied (mean age 53.9 ± 20.0 years; 19 females). Two groups resulted: tilt‐induced vasovagal syncope positive and negative. The cardiorespiratory parameters blood pressure (BP), heart rate (HR), tidal volume, and minute volume were measured. Comparisons of the cardiorespiratory parameters were made within the positive group and negative group, and then between the two groups. There were 14 in the positive group and 15 in the negative group. Baseline measurements were normalized to 1.0. Comparing the late tilt periods between the positive and negative groups, there were differences in BP (P < 0.002), HR (P < 0.002), tidal volume (P < 0.05), and minute volume (P < 0.002). In the positive group comparing early with late intervals: BP l.11 ± 0.09 versus 0.49 ± 0.17, P < 0.0001; HR 1.18 ± 0.12 versus 0.85 ±0.35, P < 0.009; tidal volume 1.39 ± 0.34 versus 2.17 ± 1.00, P < 0.015; and minute volume 1.24 ± 0.26 versus 3.3 ± 2.03, P < 0.0025. There were no comparable cardiorespiratory changes in the negative group.

Conclusion: There were significant differences in the respiratory and cardiovascular parameters measured between those who were positive and those who were negative for tilt‐induced vasovagal syncope. Within the positive group, in addition to the falls in HR and BP, there were significant increases in minute volume and tidal volume during late tilt. This suggests that there may be a role for respiratory sensors in vasovagal syncope that may permit earlier and hence possibly more effective therapy for selected patients.
Molecular Remodeling of Kv4.3 Potassium Channels in Human Atrial Fibrillation
Authors: GRAMMER JOACHIM B. , BOSCH RALPH F. , KÜHLKAMP VOLKER , SEIPEL LUDGER
Published: April 2007

Repolarizing Potassium Currents in Atrial Fibrillation, introduction: Atrial fibrillation (AF) is associated with important alterations in cardiac ion channels that cause shortening and impaired rate adaptation of atrial repolarization. The mechanisms underlying potassium current remodeling in human AF are not clear. We investigated the effects of AF on the gene expression of the Kv4.3, Kv1.4, and Kv1.5 potassium channel subunits and correlated the findings with the transient outward (I10) and the sustained outward (Isus or Ikur) potassium current.

Methods and Results: Semiquantitative reverse transcription‐polymerase chain reaction was used to evaluate mRNA expression, and ion currents were studied with the patch clamp technique in right atrial appendages from patients in AF and compared with those from patients in stable sinus rhythm (SR). The presence of AF was associated with a 61% reduction in Kv4.3 mRNA expression (P < 0.001 vs SR), which was paralleled by a reduction in Ito current densities in this group of patients (i.e., at ± 50 mV: 7.44 ± 0.76 pA/pF in SR and 1.24 ± 0.28 pA/pF in AF; P < 0.001 vs SR). mRNA levels of Kv 1.4 were identical in the two groups. AF did not affect either the gene expression of Kv 1.5 or the current densities of Isus.

Conclusion: Chronic AF in humans reduces Ito by transcriptional down‐regulation of the Kv4.3 potassium channel. Altered gene expression is an important component of the electrical remodeling process and may contribute to repolarization abnormalities in AF.
Changes in Left Ventricular Repolarization and Ion Channel Currents Following a Transient Rate Increase Superimposed on Bradycardia in Anesthetized Dogs
Authors: RUBART MICHAEL , LOPSHIRE JOHN C. , FINEBERG NAOMI S. , ZIPES DOUGLAS P.
Published: April 2007

Electrical Remodeling of the Heart due to Rate. Introduction: We previously demonstrated in dogs that a transient rate increase superimposed on bradycardia causes prolongation of ventricular refractoriness that persists for hours after resumption of bradycardia. In this study, we examined changes in membrane currents that are associated with this phenomenon.

Methods and Results: The whole cell, patch clamp technique was used to record transmembrane voltages and currents, respectively, in single mid‐myocardial left ventricular myocytes from dogs with 1 week of complete AV block; dogs either underwent 1 hour of left ventricular pacing at 120 beats/min or did not undergo pacing. Pacing significantly heightened mean phase 1 and peak plateau amplitudes by ∼6 and ∼3 mV, respectively (P < 0.02). and prolonged action potential duration at 90% repolarization from 235 ± 8 msec to 278 ± 8 msec (1 Hz; P = 0.02). Rapid pacing‐induced changes in transmembrane ionic currents included (1) a more pronounced cumulative inactivation of the 4‐aminopyridine‐sensitive transient outward K+ current, I to over the range of physiologic frequencies, resulting from a ∼30% decrease in the population of quickly reactivating channels; (2) increases in peak density of L‐type Ca2+ currents, Ica.I.' by 15% to 35% between +10 and +60 mV; and (3) increases in peak density of the Ca2+‐activated chloride current, ICl.Ca' by 30% to 120% between +30 and +50 mV.

Conclusion: Frequency‐dependent reduction in Ito combined with enhanced ICa.I. causes an increase in net inward current that may he responsible for the observed changes in ventricular repolarization. This augmentation of net cation influx is partially antagonized by an increase in outward ICa.Cl.
Contact Fluorescence Imaging of Reentry in Monolayers of Cultured Neonatal Rat Ventricular Myocytes
Authors: ENTCHEVA EMILIA , LU STEVEN N. , TROPPMAN RACHEL H. , SHARMA VINOD , TUNG LESLIE
Published: April 2007

Reentry in Cell Monolayers Imaged by CFI. Introduction: We present a novel contact fluorescence imaging (CFI) approach to monitor transmembrane potentials in monolayers of cultured neonatal rat ventricular cells. We apply CFI to demonstrate, for the first time, long‐term recordings as well as electrical induction and termination of reentrant activity in this in vitro model.

Methods and Results: CFI was performed in confluent cell monolayers stained with di‐8‐ANEPPS. An anatomic obstacle (6 × 0.5 mm) was created in the center of the monolayers. Reentry was induced with a premature stimulus after pacing at 2 Hz (both via field stimulation). Seven sustained (>3 min) reentrant episodes, anchored to the anatomic obstacle, were observed in three monolayers. Field stimulation (30 V/cm) was applied to successfully terminate 6 of the 7 reentries. Analysis of reentrant activity showed similarities with anatomic reentry in tissue preparations, such as reduced conduction velocity around the core, variable conduction velocity along the reentrant pathway due to wavefront curvature effects, and field‐induced activation at the obstacle borders leading to reentry termination (cardioversion).

Conclusion: This study demonstrates the feasibility of CFI for macroscopic optical mapping of transmembrane potentials in a single layer of cultured cells. Our results suggest that the monolayer cell culture model is an attractive complement to tissue models of reentry and cardioversion.
Long QT Syndrome:
Authors: SANGUINETTI MICHAEL C.
Published: April 2007

Point of View. Long QT syndrome type 1 (LQFI) causes torsades de pointes arrhythmia, ventricular fibrillation, and sudden death. It usually is inherited as an autosomal dominant trait (Romano‐Ward syndrome). The primary defect in LQTI is a mutation in KVLQT1, a gene that encodes the pore‐forming α‐subunit of a K+ channel. KvLQT1 α‐subunits coassemble with minK β‐subunits to form channels that conduct the slow delayed rectifier K+ current (IKs) in the heart. Recessive mutations in KVLQT1 cause Jervell and Lange‐Nielsen syndrome, which is characterized by more severe arrhythmias and congenital neural deafness. Heterologous expression studies demonstrated that mutations in KVLQT1reduce IKs by causing loss of channel function, altered channel gating, and/or a dominant‐negative effect. It remains to be proven that an understanding of the molecular basis of LQT1 will lead to more effective therapy.
Predicting the Arrhythmogenic Foci of Atrial Fibrillation Before Atrial Transseptal Procedure:
Authors: LEE SHIH‐HUANG , TAI CHING‐TAI , UN WEI‐SHIANG , TSAI CHIN‐FENG , HSIEH MING‐HSIUNG , YU WEN‐CHUNG , LIR YUNG‐KUO , CHEN CHIEN‐CHENG , DING YU‐AN , CHANG MAU‐SONG , CHEN SHIH‐ANN
Published: April 2007

Arrhythmosenic Foci of Atrial Fibrillation. Introduction: Use of endocardial atrial activation sequences from recording catheters in the right atrium. His bundle, and coronary sinus to predict the location of initiating foci of atrial fibrillation (AF) before an atrial transseptal procedure has not been reported. The purpose of the present study was to develop an algorithm using endocardial atrial activation sequences to predict the location of initiating foci of AF before transseptal procedure.

Methods and Results: Seventy‐five patients (60 men and 15 women, age 68 ± 12 years) with frequent episodes of paroxysmal AF were referred for radiofrequency ablation. By retrospective analysis, characteristics of the endocardial atrial activation sequences of right atrial, His‐bundle, and coronary sinus catheters from the initial 37 patients were correlated with the location of initiating foci of AF, which were confirmed by successful ablation. The endocardial atrial activation sequences of the other 38 patients were evaluated prospectively to predict the location of initiating foci of AF before transseptal procedure using the algorithm derived from the retrospective analysis. Accuracy of the value <0 msee (obtained by subtracting the time interval between high right atrium and His‐bundle atrial activation during atrial premature beats from that obtained during sinus rhythm) for discriminating the superior vena cava or upper portion of the crista terminalis from the pulmonary vein (PV) foci was 100%. When the interval between atrial activation ostial and distal pairs of the coronary sinus catheter of the atrial premature beats was <0 msec, the accuracy for discriminating left PV foci from right PV foci was 92% in the 24 foci from the left PVs and 100% in the 19 foci from the right PVs.

Conclusion: Endocardial atrial activation sequences from right atrial, His‐bundle, and coronary sinus catheters can accurately predict the location of initiating foci of AF before transseptal procedure. This may facilitate mapping and radiofrequency ablation of paroxysmal AF.
Atrioventricular Nodal Tachycardia Occurring During Atrial Fibrillation
Authors: CHEN JANE , JOSEPHSON MARK E.
Published: April 2007

AVNRT During Atrial Fibrillation. We describe the case of a 32‐year‐old woman with palpitations and atrial fibrillation (AF) as the only documented arrhythmia. The patient underwent electrophysiologic study and was found to have inducible AV nodal reentrant tachycardia (AVNRT). During a prolonged episode of AVNRT, AF developed in both atria, hut AVNRT persisted. Dissociation of the atria during AVNRT is evidence that the atrium is not necessary in AVNRT. This case also illustrates the utility of an electrophysiologic study in locating a potentially curable arrhythmia as the primary cause of AF in young patients.
QT Dispersion Does Not Represent Electrocardiographic Interlead Heterogeneity of Ventricular Repolarization
Authors: MALIK MAREK , ACAR BURAK , GANG YI , YAP YEE GUAN , HNATKOVA KATERINA , CAMM A. JOHN
Published: April 2007

QT Dispersion and Repolarization Heterogeneity. Introduction: QT dispersion (QTd, range of QT intervals in 12 ECG leads) is thought to reflect spatial heterogeneity of ventricular refractoriness. However, QTd may be largely due to projections of the repolarization dipole rather than “nondipolar” signals.

Methods and Results: Seventy‐eight normal subjects (47 ± 16 years, 23 women), 68 hypertrophic cardiomyopathy patients (HCM; 38 ± 15 years. 21 women), 72 dilated cardiomyopathy patients (DCM; 48 ± 15 years, 29 women), and 81 survivors of acute myocardial infarction (AMI; 63 ± 12 years, 20 women) had digital 12‐lead resting supine ECGs recorded (10 ECGs recorded in each subject and results averaged). In each ECG lead, QT interval was measured under operator review by QT Guard (GE Marquette) to obtain QTd. QTd was expressed as the range, standard deviation, and highest‐to‐lowest quartile difference of QT interval in all measurable leads. Singular value decomposition transferred ECGs into a minimum dimensional time orthogonal space. The first three components represented the ECG dipole; other components represented nondipolar signals. The power of the T wave nondipolar within the total components was computed to measure spatial repolarization heterogeneity (relative T wave residuum, TWR). OTd was 33.6 ± 18.3, 47.0 ± 19.3, 34.8 ± 21.2, and 57.5 ± 25.3 msec in normals, HCM, CM, and AMI, respectively (normals vs DCM: NS, other P < 0.009). TWR was 0.029%± 0.031%, 0.067%± 0.067%, 0.112%± 0.154%, and 0.186%± 0.308% in normals, HCM, DCM, and AMI (HCM vs DCM: NS. other P < 0.006), The correlations between QTd and TWR were r = ‐0.0446, 0.2805, ‐0.1531, and 0.0771 (P = 0.03 for HCM, other NS) in normals, HCM, DCM, and AMI, respectively.

Conclusion: Spatial heterogeneity of ventricular repolarization exists and is measurable in 12‐lead resting ECGs. It differs between different clinical groups, but the so‐called QT dispersion is unrelated to it.
Accessory Atrioventricular Node with Properties of a Typical of a Typical Accessory Pathway:
Authors: GOLLOB MICHAEL H. , BHARATI SAROJA , SWERDLOW CHARLES D.
Published: April 2007

Accessory AV Node. We report an accessory AV node producing ventricular preexcitation and comprising the retrograde limb of AV reentrant tachycardia (AVRT). A 66‐year‐old man presented with an anteroseptal myocardial infarction and thereafter developed recurrent, drug‐refractory AVRT requiring multiple cardioversions. Electrophysiologic findings were typical for a concealed anteroseptal accessory pathway 0.5 cm anterior to the His bundle. The patient died of intractable heart failure after endocardial resection for a left ventricular aneurysm and coronary bypass grafting. Pathologic examination revealed a para‐Hisian accessory AV node connecting the right atrium to ventricular myocardium immediately anterior to the His bundle at a depth of 4 mm from the endocardium. No typical AV accessory pathway was found. This is the first report of an accessory AV node that participated in AVRT. It was deeper than typical radiofrequency catheter ablation lesions.
Prevention of Ventricular Fibrillation by Pacing in a Man with Brugada Syndrome
Authors: LEE KATHY L. , LAU CHU‐PAK , TSE HUNG‐EAT , WAN SIU‐HONG , EAN KATHERINE
Published: April 2007

Pacing Prevents VF in Brugada Syndrome. The unique ECG appearance of Brugada syndrome is caused by failure of the dome of the action potential to develop. It occurs when the outward currents (mainly Ito) overwhelm the inward currents (mainly Ica) at the end of phase 1 of the action potential. Because Ito becomes less prominent at a faster rate, increased heart rate is associated with decreased ST segment elevation on ECG and probably decreased incidence of ventricular arrhythmia. We present the first report on prevention of ventricular fibrillation in a man with Brugada syndrome by overdrive pacing from his dual chamber implantable cardioverter defibrillator.
Donor‐to‐Recipient Decremental Conduction of Atrial Fibrillation Following Orthotopic Heart Transplantation:
Authors: LANDOLINA MAURIZIO , DE FERRARI GAETANO M. , CANTU FRANCESCO , CAMPANA CARLO
Published: April 2007

Donor‐to‐Recipient Decremental Conduction of AF. We describe the unique case of a heart transplant patient with type I atrial fibrillation that arose in the donor atrium during a late acute rejection episode and conducted to the recipient atrium with second‐degree type I local block. After internal cardioversion, programmed stimulation showed bidirectional decremental conduction across the suture line with nearly equal atrioatrial interval, whereas the recipient atrium showed progressively delayed intra‐atrial conduction. These findings strongly suggest that the mechanism of atrioatrial conduction may be electrical propagation along viable myocardium bridging the surgical scar and that the electrophysiologic characteristics of the recipient atrium are involved in decremental conduction across the suture line.
Are Routine Arrhythmia Inductions Necessary in Patients with Pectoral Implantable Cardioverter Defibrillators?
Authors: GLIKSON MICHAEL , LURIA DAVID , FRIEDMAN PAUL A. , TRUSTY JANE M. , BENDERLY MICHAL , HAMMILL STEPHEN C. , STANTON MARSHALL S.
Published: April 2007

Routine Arrhythmia Inductions in Patients with ICDs. Introduction: The value of ventricular arrhythmia inductions as part of routine implantable cardioverter defibrillator (ICD) follow‐up in new‐generation pectoral ICDs is unknown

Methods and Results: We performed a retrospective analysis of a prospectively collected database analyzing data from 153 patients with pectoral ICDs who had routine arrhythmia inductions at predismissal, and 3 months and 1 year after implantation. Routine predismissal ventricular fibrillation (VF) induction yielded important findings in 8.8% of patients, all in patients with implantation defibrillation threshold (DFT) ≥ 15 J or with concomitant pacemaker systems. At 3 months and 1 year, routine VF induction yielded important findings in 5.9% and 3.8% of tested patients, respectively, all in patients who had high DFT on prior testing. Ventricular tachycardia (VT) induction at predismissal, and 3 months and 1 year after implantation resulted in programming change in 37.4%, 28.1%, and 13.8% of tested patients, almost all in patients with inducible VT on baseline electrophysiologic study and clinical episodes since implantation.

Conclusion: Although helpful in identifying potentially important ICD malfunctions, routine arrhythmia inductions during the first year after ICD implantation may not be necessary in all cases. VF inductions have a low yield in patients with previously low DFTs who lack concomitant pacemakers. VT inductions have a low yield in patients without baseline Inducible VT and in the absence of clinical events. Definite recommendations regarding patient selection must await larger prospective studies as well as consensus in the medical community about what comprises an acceptable risk justifying avoidance of the costs and inconveniences of routine arrhythmia inductions.
Signal‐Averaged Isoharmonic Body Surface Maps of Patients with Ischemic Cardiomyopathy
Authors: KAVESH NEAL G. , SARANG SAMANTHA E. , GOLD MICHAEL R.
Published: April 2007

Signal‐Averaged Body Surface Maps.Introduction:Prevention of sudden arrhythmic cardiac death depends on accurate identification of individuals at high risk. Previous studies of signals recorded directly from arrhythmogenic tissue suggested that the predictive value of the signal‐averaged ECG could be enhanced by expanded temporal, spectral, and spatial analysis. Accordingly, we performed a prospective study of 192‐lead signal‐averaged body surface maps from 43 patients with ischemic cardiomyopathy referred for electrophysiologic study. Three groups were included: 15 patients with clinical ventricular tachycardia (VT), 12 patients with inducible VT, and 16 patients with non‐VT.

Methods and Results: The patients were well matched with regard to age, gender, infarct location, ejection fraction (28%± 9%), QRS duration, and incidence of nonsustained VT (96%). Isoharmonic maps of the entire cardiac cycle were constructed for each patient. The peaks of the 1–7 Hz isoharmonic maps distinguished patients with clinical VT from non‐VT and inducible VT patients (1,152 ± 273, 852 ± 283, and 808 ± 272, respectively; P = 0.003). After prospective observation for 22 ± 16 months, the combined endpoint of spontaneous sustained VT, ventricular fibrillation, appropriate defibrillator therapy, and death was predicted by inducibility of VT (relative risk 3.8, P = 0.008) and by the signal‐averaged isoharmonic body surface map (relative risk 3.1, P = 0.02).

Conclusion: These results confirm the diagnostic utility of signal‐averaged isoharmonic body surface maps in a rigorously defined patient population.
Radiofrequency Catheter Ablation of Upper Septal Idiopathic Left Ventricular Tachycardia Exhibiting Left Bundle Branch Block Morphology
Authors: SHIMOIKE EIMEI , UEDA NORIHIRO , MARUYAMA TORU , KAJI YOSHIKAZU
Published: April 2007

Upper Septal Idiopathic Left Ventricular Tachycardia. Idiopathic left ventricular (LV) tachycardia usually exhibits right bundle branch block morphology. There are only a few sporadic cases that exhibit left bundle branch block (LBBB) morphology. We report a patient whose QRS complex during ventricular tachycardia (VT) was relatively narrow (100 msec) and exhibited LBBB (precordial R wave transition between V3 and V4) and a normal frontal plane axis. This VT was ablated successfully by radiofrequency current applied to the LV upper septum, where the earliest endocardial activation was recorded.