bluuebunny/crossref_metadata_2025 huggingface dataset:
Supraventricular Arrhythmias in Children and Young Adults with Implantable Cardioverter Defibrillators
Authors: LOVE BARRY A. , BARRETT KATHLEEN S. , ALEXANDER MARK E. , BEVILACQUA LAURA M. , EPSTEIN MICHAEL R. , TRIEDMAN JOHN K. , WALSH EDWARD P. , BERUL CHARLES I.
Published: August 2003

SVT in Pediatric ICD Recipients.
Introduction: Rapidly conducted supraventricular tachycardias (SVTs) can lead to inappropriate device therapy in implantable cardioverter defibrillator (ICD) patients. We sought to determine the incidence of SVTs and the occurrence of inappropriate ICD therapy due to SVT in a pediatric and young adult population.

Methods and Results: We undertook a retrospective review of clinical course, Holter monitoring, and ICD interrogations of patients receiving ICD follow‐up at our institution between March 1992 and December 1999. Of 81 new ICD implantations, 54 eligible patients (median age 16.5 years, range 1 to 48) were identified. Implantation indications included syncope and/or spontaneous/inducible ventricular arrhythmia with congenital heart disease (30), long QT syndrome (9), structurally normal heart (ventricular tachycardia/ventricular fibrillation [VT/VF]) (7), and cardiomyopathies (7). Sixteen patients (30%) received a dual‐chamber ICD. SVT was recognized in 16 patients, with 12 of 16 having inducible or spontaneous atrial tachycardias. Eighteen patients (33%) received ≥ 1 appropriate shock(s) for VT/VF; 8 patients (15%) received inappropriate therapy for SVT. Therapies were altered after an inappropriate shock by increasing the detection time or rate and/or increasing beta‐blocker dosage. No single‐chamber ICD was initially programmed with detection enhancements, such as sudden onset, rate stability, or QRS discriminators. Only one dual‐chamber defibrillator was programmed with an atrial discrimination algorithm. Appropriate ICD therapy was not withheld due to detection parameters or SVT discrimination programming.

Conclusion: SVT in children and young adults with ICDs is common. Inappropriate shocks due to SVT can be curtailed even without dual‐chamber devices or specific SVT discrimination algorithms.
Clinical Validation of New Pacing‐Sensing Configurations for Atrial Automatic Capture Verification in Pacemakers
Authors: BUTTER CHRISTIAN , HARTUNG WOLFGANG M. , KAY G. NEAL , WILLEMS ROGER , ZHANG GENG , LANG DOUGLAS J. , FLECK ECKART
Published: August 2003

Atrial Automatic Pacing Capture Verification.
Introduction: This study evaluated an atrial automatic capture verification scheme based on atrial evoked response (AER). Atrial pacing was between Atip and Can (Atip–Can) using different coupling capacitances (CCs). Independent pairs of sensing electrodes between Aring and Vtip (Aring–Vtip) or between Aring and a separate indifferent electrode (Aring–Indiff) were used to reduce pacing‐induced afterpotentials.

Methods and Results: A custom‐made external pacing system was used to perform automatic step‐up and step‐down pacing (0.1 to 7.1 V at 0.5 msec, step size of 0.1 V) using different CCs (2 or 15 μF). Intracardiac signals from Aring–Indiff and Aring–Vtip were independently recorded and analyzed both in real time and off‐line to detect AER. Every paced beat also was visually inspected and compared with surface ECG to verify the captures. With the intracardiac signals properly filtered, AER detection was based on the signal within a window of 12 to 65 msec after the stimulus. Data from 27 patients (4 chronic and 23 acute implantations; age 65.6 ± 13.9 years) were analyzed. Bipolar atrial lead measurements using a standard pacing system analyzer were as follows (mean ± SD): impedance 695 ± 227 Ω, P wave amplitude 4.2 ± 2.3 mV, slew rate 1.1 ± 0.9 V/sec, and pacing threshold at 0.5 msec 1.0 ± 0.5 V. The results with CC = 2 μF showed that of 9,500 atrial paced beats, correct capture verification rates were 99.8% (Aring–Indiff) and 99.4% (Aring–Vtip). Similar results were achieved with CC = 15 μF (99.7% and 99.5%, respectively).

Conclusion: AER can be reliably detected using independent pacing (Atip–Can) and sensing (Aring–Vtip or Aring–Indiff) electrodes. Therefore, atrial automatic capture verification by AER detection is feasible.
Relationship Between Serum Potassium Concentration and Risk of Recurrent Ventricular Tachycardia or Ventricular Fibrillation
Authors: MICHAUD GREGORY F. , STICHERLING CHRISTIAN , TADA HIROSHI , ORAL HAKAN , PELOSI FRANK , KNIGHT BRADLEY P. , MORADY FRED , STRICKBERGER S. ADAM
Published: August 2003

Serum Potassium and Defibrillator Shocks.
Introduction: Electrolyte abnormalities are considered a correctable cause of a life‐threatening ventricular arrhythmia according to American Heart Association/American College of Cardiology Practice Guidelines, and ventricular tachycardia or ventricular fibrillation in the setting of an electrolyte abnormality is considered a class III indication for defibrillator implantation. However, there are little data to support this recommendation. The purpose of this study was to determine the risk of a recurrent sustained ventricular arrhythmia in patients with a low serum potassium concentration at the time of an initial episode of a sustained ventricular arrhythmia.

Methods and Results: One hundred sixty‐nine consecutive patients who presented with a sustained ventricular arrhythmia and a serum potassium concentration determined on the day of the arrhythmia underwent defibrillator implantation. All patients had structural heart disease and left ventricular ejection fraction of 0.32 ± 0.15. On the day of the index arrhythmia, 30% of the patients had a serum potassium concentration < 3.5 or > 5.0 mEq/L, including 7% who had a serum potassium concentration < 3.0 or > 6.0 mEq/L. For the entire cohort of patients, freedom from a recurrent sustained ventricular arrhythmia was 18% at 5 years and was not significantly different among patients with a serum potassium concentration < 3.5 mEq/L (23%), between 3.5 and 5.0 mEq/L (16%), and > 5.0 mEq/L (5%; P = 0.1).

Conclusion: The results of the present study suggest that patients with structural heart disease and an abnormal serum potassium concentration at the time of an initial episode of sustained ventricular tachycardia or ventricular fibrillation are at high risk for a recurrent ventricular arrhythmia; therefore, implantable defibrillator therapy may be reasonable.
Postmyocardial Infarction Patients Susceptible to Ventricular Tachycardia Show Increased T Wave Dispersion Independent of Delayed Ventricular Conduction
Authors: OIKARINEN LASSE , VIITASALO MATTI , KORHONEN PETRI , VÄÄNÄNEN HEIKKI , HÄNNINEN HELENA , MONTONEN JUHA , MÄKIJÄRVI MARKKU , KATILA TOIVO , TOIVONEN LAURI
Published: August 2003

Arrhythmia Markers After Myocardial Infarction.
Introduction: Experimentally, both delayed ventricular conduction and nonhomogeneous ventricular repolarization contribute to reentrant arrhythmias. We tested the hypothesis that increased T wave dispersion is independent of delayed ventricular conduction associated with arrhythmia vulnerability in postmyocardial infarction (post‐MI) patients.

Methods and Results: We studied 32 post‐MI patients with clinical or inducible monomorphic ventricular tachycardia (VT group), 28 post‐MI patients without arrhythmias (MI group), and 13 healthy controls, using magnetocardiographic (MCG) mapping with signal averaging. Twelve‐lead ECG was the reference. Filtered QRS duration (fQRS) and T wave peak to T wave end interval (TPE) were used as measures of ventricular conduction and nonhomogeneity in ventricular repolarization, respectively. In MCG, the VT group showed the longest fQRS (135 ± 34 msec vs 114 ± 22 msec in the MI group; P = 0.012). Mean TPE and maximum TPE in VT versus MI groups were 78 ± 9 msec versus 70 ± 6 msec (P < 0.001) and 117 ± 23 msec versus 104 ± 19 msec (P = 0.020), respectively. Maximum TPE did not correlate with fQRS in the VT group (r = 0.063; P = NS) but did correlate in the MI group (r = 0.396; P = 0.037). For identification of post‐MI patients prone to VT, selection of cutoff values for fQRS > 140 msec and mean TPE > 81 msec gave sensitivity and specificity of 41% and 89%, and 31% and 96%, respectively. Their combination increased sensitivity to 63% while maintaining 89% specificity.

Conclusion: Post‐MI patients susceptible to VT show increased T wave dispersion independent of delayed ventricular conduction.
Pace‐Termination and Pacing for Prevention of Atrial Tachyarrhythmias: Results from a Multicenter Study with an Implantable Device for Atrial Therapy
Authors: ISRAEL CARSTEN W. , HÜGL BURKHARD , UNTERBERG CHRISTINA , LAWO THOMAS , KENNIS INGRID , HETTRICK DOUGLAS , HOHNLOSER STEFAN H.
Published: August 2003

Pacing for Treatment of Atrial Tachyarrhythmias.
Introduction: Patients with bradycardia requiring permanent pacing frequently suffer from additional atrial tachyarrhythmias (ATs). This study evaluated the safety and efficacy of atrial antitachycardia pacing (ATP) and the performance of pacing for AT prevention implemented into a new pacemaker.

Methods and Results: In patients with conventional indications for permanent pacing, an investigational DDDRP pacemaker (Medtronic AT500, model 7253) was implanted. The primary study objectives were to determine the safety of overall device functioning and its efficacy in terminating spontaneous AT. A secondary endpoint was to determine the reliability of AT detection. Pacemaker memory functions were used to analyze the impact of dedicated pacing algorithms on AT prevention. In 33 European and Canadian centers, 325 patients were enrolled (mean follow‐up 2.3 ± 1.3 months). Complication‐free survival at 3 months was 88%. In 2,145 episodes stored with atrial electrograms, AT detection was confirmed in 97%. The algorithm for continuous overdrive pacing increased the percentage of atrial pacing to 97%. After ATP activation, 16,683 of 52,468 AT episodes were treated (120 patients). Of these, 8,903 episodes (53%) were terminated successfully by ATP. No proarrhythmic effect of preventive pacing or atrial ATP was observed. Preventive pacing algorithms increased the median percentage of atrial pacing from 62% to 97%. However, the number of AT/AF (atrial fibrillation) episodes (4.1 vs 4.1 per patient per day) and the time in AT/AF (13.7% vs 12.8%) was not significantly different before and after activation of preventive pacing.

Conclusion: DDDRP pacing with a new system for AT therapy was safe and associated with successful pace‐termination of AT in 53% of episodes. Preventive pacing and atrial ATP algorithms represent two new functions that can be implemented safely into pacemaker systems for nonpharmacologic treatment of ATs in patients requiring pacemaker therapy.
Effect of Strength and Timing of Transmembrane Current Pulses on Isolated Ventricular Myocytes
Authors: GRAY RICHARD A. , HUELSING DELILAH J. , AGUEL FELIPE , TRAYANOVA NATALIA A.
Published: August 2003

Cellular Response to Premature Stimuli.
Introduction: Little is known about how the amplitude and timing of transmembrane current pulses affect transmembrane potential (Vm) and action potential duration (APD) in isolated myocytes.

Methods and Results: Ten ventricular myocytes were isolated from five rabbit hearts. Each cell was paced at an S1 cycle length of 250 msec, and S2 pulses of 10‐msec duration were delivered at various strengths and time intervals. For all S2 strengths (0.2 to 1.5 nA), the magnitude of changes in Vm did not depend on polarity during the plateau, but were larger for depolarizing pulses during phase 3 repolarization. However, the magnitude of changes in APD varied with polarity during the entire action potential for strengths ranging from 0.5 to 1.5 nA. Greater changes in APD occurred for hyperpolarizing pulses during the plateau and depolarizing pulses during phase 3. In addition, we used a cardiac phase variable to quantify the current threshold for regenerative depolarization and repolarization as a function of prestimulus Vm. Regenerative depolarization occurred during phase 3 repolarization, and its current threshold was less than that required for regenerative repolarization that occurred during the plateau. These data were compared to computer simulations in a patch of membrane represented by Luo‐Rudy dynamic kinetics, and the results were qualitatively similar, including the higher threshold for regenerative repolarization compared to regenerative depolarization.

Conclusion: This characterization of the nonlinear response of isolated cells to transmembrane current, including phase resetting, should aid in understanding the mechanisms of defibrillation because shockinduced changes in Vm and APD have been implicated as important factors in determining defibrillation success.
Conversion of Atrial Fibrillation by the Experimental Antiarrhythmic Drug Tedisamil in Two Canine Models
Authors: FISCHBACH PETER S. , BARRETT TERRANCE D. , GOYAL RAJIVA , TRAN BINH C. , SYED ZAFFER A. , HENNAN JAMES K. , LUCCHESI BENEDICT R.
Published: August 2003

Tedisamil Conversion of AF in Two Canine Models.
Introduction: Tedisamil is an experimental bradycardic agent possessing action potential‐prolonging effects. It has been proven effective in terminating ventricular arrhythmias in several animal models and atrial flutter in a conscious dog model. There are no reports to date evaluating tedisamil's efficacy in terminating atrial fibrillation (AF).

Methods and Results: Two different canine models of AF were used. One group of dogs (n = 6) was subjected to 28 days of chronic fibrillatory pacing at 50 Hz using an implantable neural stimulator. Sustained AF was achieved in all dogs within 14 days of initiating pacing. A second set of dogs (n = 5) had AF induced via bilateral vagal stimulation. Tedisamil 1 mg/kg was 100% effective in terminating AF in both models. Cardioversion was associated with a statistically significant prolongation of the fibrillatory cycle length immediately before return to normal sinus rhythm in both models. A dose‐response trial was performed in the vagal AF group as well as in a second group of three dogs that underwent chronic fibrillatory pacing. The efficacy of tedisamil was dose dependent, with limited efficacy at 0.1 and 0.3 mg/kg intravenously in both models. Tedisamil was able to prevent reinduction of sustained AF 30 minutes after administration of 1 mg/kg in the chronic pacing model in all dogs. Side effects included minor hypersalivation in most dogs receiving the 1 mg/kg dose. No ventricular ectopy or arrhythmias were observed.

Conclusion: Tedisamil is effective for conversion of sustained AF to normal sinus rhythm in two different models of AF.
Excitation of a Cardiac Muscle Fiber by Extracellularly Applied Sinusoidal Current
Authors: VIGMOND EDWARD J. , TRAYANOVA NATALIA A. , MALKIN ROBERT A.
Published: August 2003

Sinusoidal Excitation of Cardiac Muscle Fiber.
Introduction: The goal of this study was to examine the effect of AC currents on a cardiac fiber. The study is the second in a series of two articles devoted to the subject. The initial study demonstrated that low‐strength sinusoidal currents can cause hemodynamic collapse without inducing ventricular fibrillation. The present modeling study examines possible electrophysiologic mechanisms leading to such hemodynamic collapse.

Methods and Results: A strand of cardiac myocytes was subjected to an extracellular sinusoidal current stimulus. The stimulus was located 100 μm over one end. Membrane dynamics were described by the Luo‐Rudy dynamic model. Examination of the interspike intervals (ISI) revealed that they were dependent on the phase of the stimulus and, as a result, tended to take on discrete values. The frequency dependency of the current threshold to induce an action potential in the cable had a minimum, as has been found experimentally. When a sinus beat was added to the cable, the sinus beat dominated at low‐stimulus currents, whereas at high currents the time between action potentials corresponded to the rate observed in a cable without the sinus beat. In between there was a transition region with a wide dispersion of ISIs.

Conclusion: The following phenomena observed in the initial study were reproduced and explained by the present simulation study: insignificant effect of temporal summation of subthreshold stimuli, frequency dependency of the extrasystole threshold, discrete nature of the ISI, and increase in regularity of the ISI with increasing stimulus strength.
Mechanisms by which AC Leakage Currents Cause Complete Hemodynamic Collapse Without Inducing Fibrillation
Authors: MALKIN ROBERT A. , HOFFMEISTER BRENT K.
Published: August 2003

AC‐Induced Non‐VF Collapse.
Introduction: The first study of weak alternating current (AC) stimulation in closed chest humans showed that complete hemodynamic collapse can occur below the threshold for inducing ventricular fibrillation (VF), a heretofore unknown danger to patients. This article, and the accompanying simulation article, explore the mechanisms responsible for the collapse.

Methods and Results: A quadripolar pacing catheter was placed in the right ventricle (RV) of six dogs. The tip of the catheter (17 mm2) carried 5 seconds of AC stimulation ranging from 10 to 160 Hz and 10 to 1,000 μA. The lead II body surface ECG, femoral artery pressure, and a bipole from the proximal pair of electrodes on the RV catheter were recorded 2 seconds before, during, and 2 seconds after stimulation. Based on the blood pressure, every episode was categorized as VF, COLLAPSE without VF, extrasystolic without COLLAPSE (EFFECT), or having caused no effect (NSR). The electrical activation interval (interspike interval [ISI]) from the RV bipole was compared with the mechanical activation interval, determined from M‐mode ultrasound. COLLAPSE is associated with a short ISI (NSR = 408 ± 110 msec; EFFECT = 305 ± 113 msec; COLLAPSE = 179 ± 25 msec; P < 0.001) with a high degree of regularity (P < 0.001): coefficient of variation of ISI for COLLAPSE (0.038 ± 0.069) versus VF (0.389 ± 0.222), EFFECT (0.420 ± 0.241), and NSR (0.016 ± 0.048). Electrical activation and mechanical activation rates occurred at integer multiples of the AC stimulation period.

Conclusion: COLLAPSE (86 ± 37 μA; minimum 50 μ A in two animals) occurs below the VF threshold (108 ± 28 μA) by causing rapid, regular excitation.
Theoretical and Experimental Study of Sawtooth Effect in Isolated Cardiac Cell‐Pairs
Authors: SHARMA VINOD , TUNG LESLIE
Published: August 2003

Sawtooth Effect in Cell‐Pairs.
Introduction: The question of how a defibrillation shock affects the myocardium far (> ~1 mm; the space constant of continuum tissue models) from the electrode is not fully understood. According to a long‐standing, yet to be verified, hypothesis, the relatively high‐resistance intercellular gap junctions may help in coupling the shock effect to the distant myocardium by redistributing the defibrillation current and creating a sawtooth pattern of polarization in which every cell undergoes hyperpolarization and depolarization. The goal of this study was to conduct an in‐depth theoretical and experimental investigation of the sawtooth effect in the simplest coupled system, that of an isolated cell‐pair.

Methods and Results: Theoretically, we present a relationship between sawtooth amplitude (STA) and junctional resistance (Rj), and show that, in a cell‐pair with two cells of different lengths, the sawtooth effect may not necessarily appear as a reversal in polarization across the junction when Rj is below a critical value. Experimentally, we optically mapped transmembrane potential responses along the lengths of enzymatically isolated guinea pig cell‐pairs at 10– or 17–μm resolution, and estimated STA as the magnitude of discontinuity in responses at the intercellular junction. From 14 cell‐pairs, STA was estimated to be ~11 mV for a nominal 10 V/cm field. Based on our theoretical results, this value corresponds to an Rj of ~18 M Ω.

Conclusion: The intercellular junction induces a measurable sawtooth effect in the simplest system of an isolated cell‐pair. An accounting for the sawtooth effect might be essential for understanding fieldtissue interaction far from the electrode and to accurately predict tissue response during field stimulation.
Entrainment by an Extracellular AC Stimulus in a Computational Model of Cardiac Tissue
Authors: MEUNIER JASON M. , TRAYANOVA NATALIA A. , GRAY RICHARD A.
Published: August 2003

Sinusoidal Stimulation of Cardiac Sheet.
Introduction: Cardiac tissue can be entrained when subjected to sinusoidal stimuli, often responding with action potentials sustained for the duration of the stimulus. To investigate mechanisms responsible for both entrainment and extended action potential duration, computer simulations of a two‐dimensional grid of cardiac cells subjected to sinusoidal extracellular stimulation were performed.

Methods and Results: The tissue is represented as a bidomain with unequal anisotropy ratios. Cardiac membrane dynamics are governed by a modified Beeler‐Reuter model. The stimulus, delivered by a bipolar electrode, has a duration of 750 to 1,000 msec, an amplitude range of 800 to 3,200 μA/cm, and a frequency range of 10 to 60 Hz. The applied stimuli create virtual electrode polarization (VEP) throughout the sheet. The simulations demonstrate that periodic extracellular stimulation results in entrainment of the tissue. This phase‐locking of the membrane potential to the stimulus is dependent on the location in the sheet and the magnitude of the stimulus. Near the electrodes, the oscillations are 1:1 or 1:2 phase‐locked; at the middle of the sheet, the oscillations are 1:2 or 1:4 phase‐locked and occur on the extended plateau of an action potential. The 1:2 behavior near the electrodes is due to periodic change in the voltage gradient between VEP of opposite polarity; at the middle of the sheet, it is due to spread of electrotonic current following the collision of a propagating wave with refractory tissue.

Conclusion: The simulations suggest that formation of VEP in cardiac tissue subjected to periodic extracellular stimulation is of paramount importance to tissue entrainment and formation of an extended oscillatory action potential plateau.
Iterative Atrial Tachycardia Originating from the Coronary Sinus Musculature
Authors: TRITTO MASSIMO , ZARDINI MARCO , DE PONTI ROBERTO , SALERNO‐URIARTE JORGE A.
Published: August 2003

Coronary Sinus Atrial Tachycardia. A case of iterative atrial tachycardia leading to dilated cardiomyopathy is reported. During electrophysiologic study, the tachycardia showed a markedly irregular cycle length associated with changes in atrial activation breakthrough as demonstrated by coronary sinus (CS) recordings and frequently degenerated into self‐terminating atrial fibrillation. Left atrial transseptal mapping demonstrated the earliest endocardial atrial activation close to the posterolateral mitral annulus, but this was invariably later than that recorded within the CS, where low‐energy radiofrequency applications eliminated the tachycardia. No acute vessel damage was observed at postablation CS angiography. In accordance with previously published experimental data, we hypothesized that the muscular sleeves surrounding the CS might be involved in the genesis of this tachycardia. During 6‐month follow‐up, the patient remained asymptomatic without tachycardia recurrences and with complete recovery of left ventricular function, confirming the reversible nature of the tachycardia‐induced cardiomyopathy.
Pseudo Sinus Rhythm Originating from the Left Superior Pulmonary Vein in a Patient with Paroxysmal Atrial Fibrillation
Authors: YAMANE TEIICHI , SHAH DIPEN C. , JAÏS PIERRE , HAÏSSAGUERRE MICHEL
Published: August 2003

Pseudo Sinus Rhythm Originating from a Pulmonary Vein. We report the case of a patient with paroxysmal atrial fibrillation in whom the background cardiac rhythm falsely mimicked sinus rhythm but actually originated from the left superior pulmonary vein. P waves during the ectopic rhythm were flat in lead I, negative in lead aVL, and without a typical “dome‐and‐dart” feature in precordial leads. Radiofrequency applications inside the left superior pulmonary vein eliminated both atrial fibrillation and the ectopic pacemaker.
Asymptomatic Brugada Syndrome Case Unmasked During Dimenhydrinate Infusion
Authors: PASTOR AGUSTÍN , NÚNEZ AMBROSIO , CANTALE CARINA , COSÍO FRANCISCO G.
Published: August 2003

Asymptomatic Brugada Syndrome. Typical ECG of that described for Brugada syndrome was elicited in a patient diagnosed with labyrinthopathy during infusion of dimenhydrinate, a first‐generation antihistamine usually used to treat motion sickness. Although the patient had no history of syncope or palpitations, and there was no family history of cardiac disease or sudden death, the ECG abnormality was reproduced later with intravenous flecainide, and an asymptomatic Brugada syndrome was diagnosed.
Sarcolemmal KATP Channels in the Heart: Molecular Mechanisms Brought to Light, but Physiologic Consequences Still in the Dark
Authors: FLAGG THOMAS P. , NICHOLS COLIN G.
Published: August 2003

Sarcolemmal KATP Channels in the Heart. ATP‐sensitive potassium (KATP) channels are inhibited by intracellular ATP and thus couple the metabolic state of the cell to its electrical activity. Tremendous progress has been made in the identification of the molecular basis of KATP channel function and regulation. The answer to one key question, however, has proven elusive: What are the precise conditions for, and functional consequences of, sarcolemmal KATP activation in physiologic and pathophysiologic states? Here we consider recent studies of the molecular basis of cardiac KATP channel activity and the role of these channels in cardiac function during ischemia.
Report of the NASPE Policy Conference on Arrhythmias and the Athlete
Authors: ESTES N.A. MARK , LINK MARK S. , CANNOM DAVID , NACCARELLI GERALD V. , PRYSTOWSKY ERIC N. , MARON BARRY J. , OLSHANSKY BRIAN
Published: August 2003

Arrhythmias and the Athlete.
Introduction: This consensus statement summarizes the proceedings of The Expert Consensus Conference on Arrhythmias in the Athlete of the North American Society of Pacing and Electrophysiology (NASPE) on detecting, evaluating, and treating athletes with cardiovascular disorders that predispose to cardiac arrhythmias.

Methods and Results: The participants in the open policy conference were selected by the codirectors (Drs. Estes and Olshansky) based on expertise and contributions to the literature. All participants provided a referenced summary of their presentation. The writing group used the information from all published scientific studies, clinical trials, registries, clinical experience, and expert opinion to make recommendations regarding screening, evaluation, management, eligibility for competition, and a range of other medical, social, and legal issues regarding the recreational and competitive athlete. The codirectors of the symposium synthesized the participants' reports for this and made revisions according to suggestions of all members of the writing committee. The manuscript was reviewed by four independent reviewers assigned by the NASPE Committee for the Development of Position Statements and NASPE Board of Trustees.

Conclusion: Despite considerable advances in knowledge regarding the diagnosis, therapy, and mechanisms of arrhythmias in the athlete, much remains unknown. Continued basic, clinical, and epidemiologic research is needed. Current screening techniques to detect athletes lack sensitivity and specificity. Evaluation of standardized screening programs with tracking of long‐term outcomes is needed. Officials from athletic, academic, medical, and legal institutions need to form strategic partnerships to develop policy related to assessment of risk and assumption of responsibility for athletic activities.
Evidence for a Single Nucleotide Polymorphism in the KCNQ1 Potassium Channel that Underlies Susceptibility to Life‐Threatening Arrhythmias
Authors: KUBOTA TOMOYUKI , HORIE MINORU , TAKANO MAKOTO , YOSHIDA HIDETADA , TAKENAKA KOTOE , WATANABE EIICHI , TSUCHIYA TAKESHI , OTANI HIDEO , SASAYAMA SHIGETAKE
Published: August 2003

Ion Channel Polymorphism and Cardiac Arrhythmia.
Introduction: Congenital long QT syndrome (LQTS) is a genetically heterogeneous arrhythmogenic disorder caused by mutations in at least five different genes encoding cardiac ion channels. It was suggested recently that common polymorphisms of LQTS‐associated genes might modify arrhythmia susceptibility in potential gene carriers.

Methods and Results: We examined the known LQTS genes in 95 patients with definitive or suspected LQTS. Exon‐specific polymerase chain reaction single‐strand conformation polymorphism and direct sequence analyses identified six patients who carried only a single nucleotide polymorphism in KCNQ1 that is found in ˜ 11% of the Japanese population. This 1727G> A substitution that changes the sense of its coding sequence from glycine to serine at position 643 (G643S) was mostly associated with a milder phenotype, often precipitated by hypokalemia and bradyarrhythmias. When heterologously examined by voltage‐clamp experiments, the in vitro cellular phenotype caused by the single nucleotide polymorphism revealed that G643S‐KCNQ1 forms functional homomultimeric channels, producing a significantly smaller current than that of the wild‐type (WT) channels. Coexpression of WT‐KCNQ1 and G643S‐KCNQ1 with KCNE1 resulted in ˜ 30% reduction in the slow delayed rectifier K+ current IKs without much alteration in the kinetic properties except its deactivation process, suggesting that the G643S substitution had a weaker dominant‐negative effect on the heteromultimeric channel complexes.

Conclusion: We demonstrate that a common polymorphism in the KCNQ1 potassium channel could be a molecular basis for mild IKs dysfunction that, in the presence of appropriate precipitating factors, might predispose potential gene carriers to life‐threatening arrhythmias in a specific population.
Relation Between Body Surface Mapping and Endocardial Spread of Ventricular Activation in Postinfarction Heart
Authors: VAN DESSEL PASCAL F.H.M. , VAN HEMEL NORBERT M. , DE BAKKER JACQUES M.T. , LINNENBANK ANDRÉ C. , POTSE MARK , JESSURUN EMILE R. , SIPPENSGROENEWEGEN ARNE , WEVER ERIC F.D.
Published: August 2003

Body Surface Mapping and Endocardial Activation Patterns.
Introduction: Body surface mapping (BSM) can be used to identify the site of earliest endocardial activation of ventricular tachycardias (VTs). The multielectrode QRS morphology during VT is determined by both the site of earliest activation and the subsequent spread of electrical activation through the ventricles. This study investigated the relationship between the site of earliest endocardial activation, endocardial spread of activation, and the morphology of the multielectrode surface map in patients with remote myocardial infarction.

Methods and Results: In 14 patients with VT late (8.2 ± 5.2 years) after myocardial infarction, BSM and simultaneous left ventricular 64‐site basket endocardial mapping was performed during a total of 17 monomorphic VTs. In addition, multisite pacing by sequential use of the 64 basket electrodes was performed in 9 patients. BSM and basket mapping revealed the same endocardial breakthrough sites in 8 (47%) of 17 VTs and 189 (59%) of 322 pacing sites; adjacent sites were found in 2 (12%) of 17 VTs and 36 (11%) of 322 pacing sites. Large zones of conduction block explained the mismatch in localization in 2 (12%) of 17 VTs and 52 (16%) of 322 pacing sites. Regional differences in endocardial electrogram amplitudes were found as a cause for dissimilarity in 3 (18%) of 17 VTs and 73 (23%) of 322 pacing sites. Multiple endocardial breakthrough sites were found in 1 (6%) of 17 VTs and 8 (2%) of 322 pacing sites Finally, an epicardial exit site was suggested in 3 (18%) of 17 VTs as an explanation for mismatch, as no early endocardial activity could be recorded.

Conclusion: Zones of conduction block, regional differences in signal amplitude, and multiple endocardial breakthrough sites are frequent causes for mismatch between BSM and basket catheter activation mapping.
Hyperventilation Facilitates Induction of Supraventricular Tachycardia: A Novel Method and the Possible Mechanism
Authors: CHEN CHIEN‐CHENG , CHEN SHIH‐ANN , TAI CHING‐TAI , KUO TERRY B.J. , CHANG MAU‐SONG , PRYSTOWSKY ERIC N.
Published: August 2003

Hyperventilation and Supraventricular Tachycardia.
Introduction: Hyperventilation has been demonstrated to alter autonomic function. Sympathomimetic drugs (isoproterenol) and parasympatholytic drugs (atropine) may be needed to facilitate induction of supraventricular tachycardia (SVT). The aim of this study was to test the clinical utility and mechanisms of hyperventilation to facilitate SVT initiation.

Methods and Results: Fourteen patients with clinically documented SVT (9 AV nodal reentrant tachycardia and 5 AV reciprocating tachycardia) but noninducible during baseline electrophysiologic study were included. Immediately after hyperventilation test (at least 30 respirations/min) for 2 minutes, systolic blood pressure, sinus cycle length, anterograde and retrograde 1:1 conduction, and induced SVT were measured. Arterial blood gas, pH, and heart rate variability before and after hyperventilation were measured. Seven of nine patients with AV nodal reentrant tachycardia and 3 of 5 patients with AV reciprocating tachycardia could be induced immediately after the hyperventilation test. After hyperventilation, anterograde AV and retrograde VA 1:1 conduction were improved, sinus cycle length was decreased, and heart rate variability were decreased in both groups.

Conclusion: Hyperventilation can facilitate induction of SVT. Improvement of conduction properties and changes of autonomic function are the possible mechanisms.
Clinical Experience with a Dual‐Chamber Implantable Cardioverter Defibrillator to Treat Atrial Tachyarrhythmias
Authors: GOLD MICHAEL R. , SULKE NEIL , SCHWARTZMAN DAVID S. , MEHRA RAHUL , EULER DAVID E.
Published: August 2003

Dual‐Chamber ICD and Atrial Tachyarrhythmia.
Introduction: This study evaluated the safety and efficacy of a new dual‐chamber implantable cardioverter defibrillator (ICD) to detect and treat atrial tachyarrhythmias in patients with drug‐refractory atrial fibrillation (AF) and no indication for a ventricular ICD.

Methods and Results: A dual‐chamber ICD (Medtronic 7250 Jewel AF) was implanted in 144 of 146 patients. The device discriminates atrial tachycardia from AF based on cycle length and regularity, and uses atrial overdrive pacing as well as shocks to terminate tachyarrhythmia episodes. Patients were followed for an average of 12.6 ± 6.2 months. Use of antiarrhythmic drugs was 63% at baseline and did not change over time. Kaplan‐Meier estimates of 12‐month complication‐free survival, device therapy survival, and patient survival were 85%, 91%, and 98%, respectively. Positive predictive accuracy of spontaneous atrial tachyarrhythmia detection was 99%, while atrial overdrive pacing and shocks terminated 40% and 87% of treated episodes, respectively. Median duration of successfully treated episodes was 8.9 minutes versus 144 minutes for the therapy failures. There was no reduction in the use of patient‐activated shock therapy over time; at the 12‐month follow‐up evaluation, 94% of patients were in sinus rhythm. Ventricular tachyarrhythmias (67 episodes) were detected and appropriately treated in 7.6% of patients.

Conclusion: This dual‐chamber ICD appears to be safe and well tolerated in patients with drug‐refractory symptomatic atrial tachyarrhythmias. The device, used in combination with drugs, effectively treats atrial tachyarrhythmias with pacing and/or shock therapies and decreases the median episode duration. In addition, the device protects from ventricular tachyarrhythmias in patients with AF and structural heart disease.
Ventricular Echo Beats and Retrograde Atrioventricular Nodal Exits in the Dog Heart: Multiplicity in Their Electrophysiologic and Anatomic Characteristics
Authors: TOSHIDA NOBUO , HIRAO KENZO , YAMAMOTO NAOHITO , TANAKA MICHIO , SUZUKI FUMIO , ISOBE MITSUAKI
Published: August 2003

Ventricular Echo Beats and Retrograde AV Nodal Exits.
Introduction: A single ventricular echo beat frequently is induced in the dog heart by ventricular pacing, but it has not been investigated using a concomitant ablative technique. We studied the effects of ablating the anterior atrial input to the AV node on ventricular echo beats induced in the dog heart to evaluate their electrophysiologic characteristics, the anatomic reentrant circuit, and the retrograde AV nodal exits.

Methods and Results: In 20 dogs, an epicardial radiofrequency current was applied to the right anterior septum in an attempt to ablate the anterior input to the AV node. Ventricular programmed stimulation was performed to evaluate the ventricular echo beat and the retrograde AV nodal exit before and after ablation. The AV junction was examined with light microscopy. Seventeen dogs in which the PR interval was prolonged significantly from 108 ± 17 msec to 153 ± 19 msec (P < 0.001) were selected for ventricular echo evaluation; 3 dogs in which persistent second‐ or third‐degree AV block was induced by ablation were excluded. Ventricular echo beats, which were induced in 13 of 17 dogs, were classified into the anterior type (n = 6) or posterior type (n = 7) according to the earliest atrial activation site during the echo beat. The retrograde AV nodal exit site showed anterior‐exit only (n = 10), posterior‐exit only (n = 2), and dual‐exit (n = 5) patterns. After ablation, the anterior‐type ventricular echo beat was noninducible in all 6 dogs, whereas the posterior‐type ventricular echo beat was noninducible in only 3 of 7 dogs. In 17 dogs, VA conduction was not demonstrated after ablation in 3 dogs, all of which showed the anterior‐exit only pattern.

Conclusion: The effect of ablation on the ventricular echo beats and retrograde AV nodal exit site suggests multiplicity in their electrophysiologic and anatomic characteristics in the dog heart.
Evolution of Action Potential Propagation and Repolarization in Cultured Neonatal Rat Ventricular Myocytes
Authors: MEIRY GIDEON , REISNER YOTAM , FELD YAIR , GOLDBERG STANISLAV , ROSEN MICHAEL , ZIV NOAM , BINAH OFER
Published: August 2003

Maturation of Cultured Neonatal Rat Ventricular Myocytes.
Introduction: Cultured neonatal rat ventricular myocytes (NRVM) reestablish gap junctions as they form synchronously and spontaneously beating monolayers, thus providing a useful model for studying activation and repolarization.

Methods and Results: We used the multielectrode array data acquisition system with 60 unipolar electrodes to investigate the functional organization of cultured NRVM, by determining propagation and repolarization patterns. Activation maps were constructed from the local activation times at each electrode. During days 3 to 8 in culture, QRS amplitude and dV/dtmax increased with age. Concomitantly, with the culture maturation, QT interval (representing action potential duration) decreased, and T wave amplitude and slopes of the T wave ascending and descending limbs progressively increased. The changes in conduction velocity were different than those of the electrogram properties, slightly increasing during the first 3 to 5 days and gradually declining toward day 8 in culture.

Conclusion: Establishment of uniform activation patterns in spontaneously firing or driven myocytes in monolayer cultures is accompanied by organization of activation and repolarization whose evolution appears in concert with that of a mature connexin43 staining pattern. The experimental techniques developed in this study provide useful tools to investigate the complex relations among gap junctions, conduction velocity, and propagation patterns, as well as a means to learn how gap junctional remodeling under pathophysiologic conditions predisposes the myocardium to arrhythmias.
Feasibility of a Left Atrial Electrical Disconnection Procedure for Atrial Fibrillation Using Transcatheter Radiofrequency Ablation
Authors: BETTS TIM R. , ROBERTS PAUL R. , MORGAN JOHN M.
Published: August 2003

Transcatheter Left Atrial Electrical Disconnection.
Introduction: An effective, catheter‐based treatment for persistent atrial fibrillation (AF) remains elusive. This study assessed the feasibility of transcatheter left atrial (LA) electrical disconnection and its effect on AF inducibility.

Method and Results: Thirteen anesthetized swine underwent noncontact mapping of the right atrium (RA) during coronary sinus (CS) pacing. Sites of earliest RA activation were identified using isopotential maps. An ablation catheter was navigated to these sites and a cluster of radiofrequency (RF) lesions applied until earliest activation shifted to a new site. The procedure was repeated until the atria were electrically disconnected. AF induction was attempted before and after ablation. Earliest RA activation was the CS os during proximal CS pacing and Bachmann's bundle during distal CS pacing. These two sites were successfully ablated in all 13 animals. Earliest activation then shifted to the fossa ovalis. RF energy was applied at a median of 2.5 sites (range 1 to 5) around the fossa, then at sites in the triangle of Koch, septum, cavotricuspid isthmus, and posterior wall. Atrial electrical disconnection was achieved in 10 of 13 animals (5 LA electrical disconnection, 3 RA electrical disconnection, 2 biatrial electrical disconnection with complete heart block). After atrial electrical disconnection, the LA became electrically silent. Before ablation, AF was inducible in every animal. After atrial electrical disconnection, AF was inducible in 3 of 10 animals.

Conclusion: Atrial electrical disconnection is feasible using noncontact mapping and RF ablation. Successful electrical disconnection of the atria reduces AF inducibility. This approach is worthy of further evaluation as a management strategy for persistent AF, combined with device therapies.
Monophasic Action Potential Recordings from Intact Mouse Heart: Validation, Regional Heterogeneity, and Relation to Refractoriness
Authors: KNOLLMANN BJÖRN C. , KATCHMAN ALEXANDER N. , FRANZ MICHAEL R.
Published: August 2003

MAP Recordings from Mouse Heart.
Introduction: The monophasic action potential (MAP) technique has been validated in humans and larger animals, but, in mice, MAP recordings available to date show little resemblance to the murine ventricular transmembrane action potential (TAP) measured by conventional microelectrodes. We developed a miniaturized MAP contact electrode technique to establish in isolated mouse hearts: (1) optimal electrode size; (2) validation against TAP; (3) relationship between repolarization and refractoriness; and (4) regional repolarization differences.

Methods and Results: In 30 Langendorff‐perfused mouse hearts, MAP electrodes of tip diameter 1.5, 1.0, and 0.25 mm were tested by comparing MAPs and TAPs from epicardial and endocardial surfaces of both ventricles. Only the MAP contact electrode of 0.25‐mm tip diameter consistently produced MAP recordings that had wave shapes nearly identical to TAP recordings. MAP durations measured at 30%, 50%, 70%, and 90% repolarization (APD30, APD50, APD70, APD90) highly correlated with TAP measurements (r = 0.97, P < 0.00001). APD50 was significantly longer in endocardial than in epicardial recordings (right ventricle: 9.3 ± 1.1 msec vs 3.9 ± 1.1 msec; left
 ventricle: 9.9 ± 2.1 msec vs 6.2 ± 1.9 msec; both P < 0.001), demonstrating transmural repolarization differences. Effective refractory period (ERP) determined at basic cycle lengths from 70 to 200 msec correlated with 80% ± 6% of total repolarization, with an ERP/APD90 ratio of 0.85 ± 0.14.

Conclusion: Murine myocardial repolarization, regional repolarization heterogeneity, and relation to refractoriness can be assessed reliably by this miniaturized MAP contact electrode technique, which renders action potential wave shapes similar to that of intracellular microelectrodes. This technique may be useful for exploring repolarization abnormalities in genetically altered mice.
In Vivo Electrophysiologic Studies in Endothelial Nitric Oxide Synthase (eNOS)‐Deficient Mice
Authors: RAKHIT AMIT , MAGUIRE COLIN T. , WAKIMOTO HIROKO , GEHRMANN JOSEF , LI GORDON K. , KELLY RALPH A. , MICHEL THOMAS , BERUL CHARLES I.
Published: August 2003

Electrophysiologic Studies in eNOS‐Deficient Mice.
Introduction: Endothelial nitric oxide synthase (eNOS) mediates attenuation of the L‐type calcium channel and modulates myocyte contractility. Arrhythmogenic afterdepolarizations are seen in vitro in ouabain‐treated isolated myocytes from eNOSdeficient mice. The aim of these studies was to characterize the baseline electrophysiologic (EP) phenotype of eNOS‐deficient mice and their potential susceptibility to cardiac conduction abnormalities and inducible arrhythmias.

Methods and Results: Surface ECG and in vivo intracardiac EP studies were performed in 27 mice lacking the eNOS gene and 21 wild‐type littermate control mice. Baseline studies were performed in 10 eNOS‐deficient mice and 10 wild‐type controls. Subsequently, 17 eNOS‐deficient mice and 11 wild‐type controls were pretreated with digoxin, and ECG and EP testing were repeated. Data analysis revealed no significant differences in ECG intervals or cardiac conduction parameters, except sinus cycle length was higher in eNOS‐deficient mice than wild‐type mice (P < 0.01). After digoxin pretreatment, 7 of 17 eNOS‐deficient mice had inducible ventricular tachycardia and 2 others had frequent ventricular premature beats, compared with only 3 of 11 wild‐type mice with inducible ventricular tachycardia. In addition, 2 digoxin‐treated eNOS‐deficient mice and 1 wild‐type mouse had inducible nonsustained atrial fibrillation.

Conclusion: Mice with a homozygous targeted disruption of the eNOS gene have slower heart rates but no other distinguishable EP characteristics under basal sedated conditions. Partial inhibition of the Na+/K+ ATPase pump with digoxin administration increases ventricular ectopic activity in eNOS–/– mice, a phenotype analogous to afterdepolarizations seen in vitro in this eNOS‐deficient mouse model.
Benefit of Pacing and Beta‐Blockers in Idiopathic Repetitive Polymorphic Ventricular Tachycardia
Authors: PÉREZ‐CASTELLANO NICASIO , RODRÍGUEZ JUAN C. , MEDINA OLGA , NIETO VICENTE
Published: August 2003

Pacing and Beta‐Blockers in Repetitive Polymorphic VT. An 18‐year‐old woman presented with recurrent exercise‐induced syncopal episodes and severe systolic dysfunction. ECG monitoring disclosed repetitive polymorphic ventricular complexes, paroxysms of bidirectional ventricular tachycardia, and nonsustained bursts of slow polymorphic ventricular tachycardia that increased in length and rate during exercise. Ventricular arrhythmias were refractory to medical treatment, which included verapamil and beta‐blockers. Addition of permanent atrial pacing to beta‐blocker therapy suppressed the arrhythmias and reversed systolic impairment in the following months.
Localization of the Origin of Arrhythmias for Ablation: From Electrocardiography to Advanced Endocardial Mapping Systems
Authors: DARBAR DAWOOD , OLGIN JEFFREY E. , MILLER JOHN M. , FRIEDMAN PAUL A.
Published: August 2003

Localization of Arrhythmias. Radiofrequency catheter ablation techniques have had a dramatic impact on the treatment of a variety of cardiac arrhythmias. However, catheter ablation of complex arrhythmias, such as intra‐atrial reentry, ventricular tachycardias, and atrial fibrillation, continues to pose a major challenge. This stems from limitations of fluoroscopy and conventional catheter‐based mapping techniques that limit the accurate anatomic localization of complex arrhythmogenic substrates. In this article, ECG features of complex arrhythmias are reviewed, which may facilitate the planning of an ablation procedure. The physical principles of the newly available catheter‐based endocardial mapping techniques and their clinical applicability for treatment of complex arrhythmias are discussed. The role of intracardiac echocardiography to facilitate mapping and ablation is reviewed.