bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Antiarrhythmic Drugs
Authors: SINGH BRAMAH N.
Published: April 2007

Current Antiarrhythmic Drugs. Reorientation in drug therapy to control cardiac arrhythmias continues to evolve in the wake of ongoing refinements in techniques and indications for radiofrequency ablation and the use of implantable devices for atrial and ventricular arrhythmias. The role of sodium channel blockers continues to be questioned, and data from clinical trials indicate that the use of this class of drugs should be limited to control symptoms in patients who have arrhythmias and either no or minimal heart disease. The decline in the use of sodium channel Blockers has led to greater use of beta blockers and complex Class III agents, such as sotalol and amiodarone, as both primary therapy and adjunctive therapy with implantable defibrillators in patients with cardiac disease of varying degrees of ventricular dysfunction. Success with these Class III agents in the context of their side effects has led to the synthesis and characterization of compounds with simpler ion channel‐blocking properties. The need for such compounds stemmed from the observation that atrial fibrillation (AF) as an arrhythmia is, for the most part, still not amenable to curative therapy by interventional procedures. The isolated block of the rapid component of the delayed rectifier current (Ikr) has been found to have either a neutral (e.g., dofetilide) or deleterious (e.g., d‐sotalol) effect on mortality in survivors of myocardial infarction. Thus, the objective of drug development should he the appropriate match between the substrate and an antiarrhythimic drug. The so‐called pure Class III agents have been shown to have beneficial antifibrillatory effects in patients with AF. They are effective in inducing acute chemical conversion, preventing paroxysmal AF, and maintaining sinus rhythm in patients with persistent AF restored to sinus rhythm with DC cardioversion. AF is a complex arrhythmia, undoubtedly a result of multifaceted derangement of atrial ionic currents. Attention has therefore focused on newer compounds that have the propensity to block more than one ion channel. Examples of such agents are tedisamil and azimilide, the latter having been studied extensively in humans. It is the first of the Class 111 agents that block both components (IKr) and IKs) of the delayed rectifier current, which results in a spectrum of electrophysiologic properties that includes lack of rate or use dependency in terms of effect on repolarization and refractoriness of atrial and ventricular myocardium. Available but unpublished clinical data indicate that azimilide may be effective over a wide range of tachycardia cycle lengths with a low incidence of torsades de pointes. In these respects, its properties, at least in terms of its use in AF, resemble those of amiodarone. However, the drug has little or no effect on AV conduction, which precludes the modulation of ventricular response in patients relapsing to AF.
Predicting Antiarrhythmic Performance
Authors: PRATT CRAIG M.
Published: April 2007

Predicting Antiarrhythmic Performance. Antiarrhythmic therapy in the past was guided by observational studies. However, optimum patient care now demands evidence derived from large clinical trials. Unfortunately, because large‐scale mortality trials are expensive and time consuming, surrogate markers were used in many clinical studies. However, the use of surrogate markers for antiarrhythmic drug efficacy was called into question after the publication of studies such as the Cardiac Arrhythmia Suppression Trial (CAST) and the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial. Currently, in order to predict antiarrhythmic performance, clinicians must rely on mortality trials for guidance in treating atrial and ventricular arrhythmias. Although the practicing physician has a large number of studies to draw from, the study design and patient population are critical variables that must be understood before trial results can be applied to patient care. This review focuses on the results of the major clinical antiarrhythmic drug trials published in the last 10 years. Patient variables (e.g., the presence or absence of structural heart disease) and problems in study design that may have affected outcome are emphasized as an aid to interpreting results of current and future clinical trials.
What Should We Expect From the Next Generation of Antiarrhythmic Drugs?
Authors: CAMM A. JOHN , YAP YEE GUAN
Published: April 2007

The Next Generation of Antiarrhythmic Drugs. Five drugs currently constitute approximately 70% of the world market for antiarrhythmic medications. Since the publication of studies documenting that certain Class I drugs may increase mortality in high‐risk postinfarction patients, basic science and clinical studies have focused on Class III antiarrhythmic drugs. However, drugs that prolong repolarization and cardiac refractoriness are sometimes associated with potentially lethal torsades de pointes. Amiodarone, a multichannel blocker, may he the exception to this observation, but it nevertheless fails to reduce total mortality compared with placebo in high‐risk patients following myocardial infarction. However, Class HI agents remain the focus of drug development efforts because they lack the negative hemodynamic effects, affect both atrial and ventricular tissue, and can be administered as either parenteral or oral preparations. Developers of newer antiarrhythmic agents have focused on identifying antiarrhythmic medications with the following characteristics: appropriate modification of the arrhythmia substrate, suppression of arrhythmia triggers, efficacy in pathologic tissues and states, positive rate dependency, appropriate pharmacokinetics, equally effective oral and parenteral formulations, similar efficacy in arrhythmias and their surrogates, few side effects, positive frequency blocking actions, and cardiac‐selective ion channel blockade. New and investigational agents that more closely approach these goals include azimilide, dofetilide, dronedarone, ersentilide, ibutilide, tedisamil, and trecetilide. In the near future, medications will increasingly constitute only part of an antiarrhythmic strategy. Instead of monotherapy, they will often be used in conjunction with an implanted device. Combination therapy offers many potential advantages. Long‐term goals of antiarrhythmic therapy include upstream approaches, such as identification of the biochemical intermediaries of the process and, eventually, of molecular and genetic lesions involved in arrhythmogenesis.
Right Atrial Focal Atrial Fibrillation
Authors: CHEN SHIH‐ANN , TAI CHING‐TAI , YU WEN‐CHUNG , CHEN YI‐JEN , TSAI CHIN‐FENG , HSIEH MING‐HSIUNG , CHEN CHIEN‐CHENG , PRAKASH V.S. , DING YU‐AN , CHANG MAU‐SONG
Published: April 2007

Focal Atrial Fibrillation. Introduction: Information about focal atrial fibrillation (AF) originating from the right atrium bas not been well described. The purposes of this study were to demonstrate the electrophysiologic characteristics and radiofrequency catheter ablation in patients who bad right atrial focal AF.

Methods and Results: From January 1996 to September 1998, 172 patients with clinically documented attacks of paroxysmal AF were referred to this institution for electrophysiologic study and/or radiofrequency catheter ablation. Anterior free wall, crista terminalis, and right and left superior pulmonary veins were mapped simultaneously. Eight patients (4.7%) had right atrial focal AF, consistent activation sequence, irregular fibrillation interval (mean fibrillation interval: 164 ± 11 msec), and episodes of exit block from the initiating foci observed. The presumed ablation site was chosen on the basis of the earliest bipolar activity relative to an atrial electrogram reference during the initiation of AF. After application of 2 ± 1 radiofrequency pulses, AF was eliminated without recurrence during the follow‐up period (mean: 14 ± 8 months: range: 3 to 25). Twenty‐four‐hour Holter monitoring showed that the number of atrial premature beats decreased significantly at the 3‐month follow‐up (4,216 ± 411 vs 135 ± 14 beats/day).

Conclusion: Right atrial focal AF is one subgroup of focal AF, and it can be cured by radiofrequency catheter ablation.
Histopathologic Effects of Radiofrequency Catheter Ablation in Previously Infarcted Human Myocardium
Authors: GRUBMAN ERIC , PAVRI BEHZAD B. , LYLE STEPHEN , REYNOLDS CAROL , DENOFRIO DAVID , KOCOVIC DUSAN Z.
Published: April 2007

Radiofrequency Ablation in Infarcted Myocardium. Introduction: The use of catheter‐based radiofrequency (RF) ablation for the treatment of ventricular tachyarrhythmias due to previous myocardial infarction has been steadily increasing. The histopathologic changes caused by this technique are not well described in humans.

Methods and Results: Three patients with hemodynamically tolerated ventricular tachycardias (VTs) due to previous myocardial infarction underwent endocardial mapping and catheter based RF ablation. All patients received between 5 and 11 RF lesions each of 60‐second duration. One patient underwent myocardial resection of a left ventricular aneurysm 1 day following RF ablation, one expired 7 days after RF ablation, and one expired 9 months after RF ablation. None of the deaths occurred as a result of RF ablation. Pathologic specimens obtained early after RF ablation revealed areas of focal acute Inflammation and fibrin deposition. Later specimens revealed several focal areas of fibrosis and granulation tissue. Specimens obtained late after RF ablation revealed a dense band of fibrosis, measuring 17 × 17 × 5 mm (1,250 mm3).

Conclusion: Catheter‐based RF ablation of ischemic VT in humans causes lesions that Initially resemble coagulation necrosis. This is followed by the development of an inflammatory infiltrate and, finally, the development of fibrosis. Repeated application of RF ablation may result in much larger lesions than have been previously reported.
Transmural Atrial Pacing in Patients with Postoperative Congenital Heart Disease
Authors: JOHNSRUDE CHRISTOPHER L. , BACKER CARL L. , DEAL BARBARA J. , STRASBURGER JANETTE F. , MAVROUDIS CONSTANTINE
Published: April 2007

Transmural Pacing in Congenital Heart Disease. Introduction: Some patients with postoperative congenital heart disease require permanent cardiac pacing, but the use of transvenous or epicardial pacing leads may be limited by type of cardiac malformation, venous connections, body size, or fibrosis. Transmural atrial pacing may provide an alternative in difficult patients, but to date has been described in only a few articles with small patient numbers, and data from lead performance are lacking.

Methods and Results: Records were reviewed in 18 consecutive patients (4 months to 21 years old) with postoperative congenital heart disease receiving transmural atrial pacing leads from July 1994 to December 1996. Implantation materials and techniques were described. Lead sensing and capture thresholds obtained acutely and during short‐term follow‐up (mean: 11.0 months) were evaluated, and comparisons were made between patients with postoperative Fontan anatomy and non‐Fontan patients, and between patients receiving steroid‐eluting and nonsteroid leads. Overall, the median acute sensing and capture thresholds of transmural leads were 4.1 mV and 0.7 V at 0.5 msec, respectively. Median follow‐up thresholds were 2.8 mV and 0.8 V, respectively. Performance of leads in Fontan patients was similar to those in non‐Fontan patients. Steroid‐eluting leads had a chronic capture threshold of 0.6 V versus 0.9 V for nonsteroid leads (P = 0.038).

Conclusion: Transmural atrial pacing leads were successfully implanted in patients with diverse ages and types of postoperative congenital heart disease. Lead performance was acceptable both acutely and during the first year of follow‐up.
Morphological and Physiological Characteristics of Discontinuous Linear Atrial Ablations During Atrial Pacing and Atrial Fibrillation
Authors: MITCHELL MARK A. , McRURY IAN D. , EVERETT THOMAS H. , LI HUI , MANGRUM J. MICHAEL , HAINES DAVID E.
Published: April 2007

Discontinuous Atrial Ablations. Introduction: Linear atrial ablations are thought to he necessary to accomplish successful catheter ablation of atrial fibrillation. In order to investigate the conduction characteristics of atrial myocardium in regions of linear lesion discontinuity gaps), we performed activation sequence mapping in gap regions during atrial pacing and atrial fibrillation.

Methods and Results. In seven dogs, a linear epicardial ablation was created on the right atrial free wall with a discontinuous segment (gap) in the mid‐portion of the lesion. A plaque electrode was used to measure conduction across the gap. Conduction was assessed during (1) atrial pacing from the edge of the plaque electrode during sinus rhythm, and (2) during atrial fibrillation. After each series of measurements, the lesion gap was decreased by creating additional radiofrequency ablations and repeat conduction maps were obtained. The process was repeated until conduction block was observed during atrial pacing. Gap lengths ranged from 0 to 25 mm. During atrial pacing, gaps as narrow as 2 mm demonstrated normal conduction and gaps as large as 5 mm demonstrated block during pacing. Although conduction block was never present across gaps greater than 5 mm, the ability to predict conduction block as a function of gap width was difficult for lesions ≤ 5 mm due to a significant degree of overlap between normal conduction and conduction block in this gap range. During atrial fibrillation, 1/175 (0.6%) mapped wavelets conducted across gaps that demonstrated block during pacing; whereas, 411/600 (68.5%; P < 0.0001) wavelets conducted across gaps that did not demonstrate block during pacing (P = NS compared to preablation measurements). Histologically normal atrial myocytes were observed within gaps exhibiting conduction block.

Conclusions: Visible gaps > 5 mm rarely demonstrate conduction block during atrial pacing and atrial fibrillation; whereas, gaps ≤ 5 mm in length may demonstrate block. Lesion gaps that do not demonstrate conduction block during atrial pacing have no higher rate of functional conduction block during atrial fibrillation than fibrillating atria without ablation lesions.
Optimal Management with Class I and Class III Antiarrhythmic Drugs Should Be Done in the Outpatient Setting
Authors: THIBAULT BERNARD , NATTEL STANLEY
Published: April 2007

Outpatient Initiation of Antiarrhythmic Drugs for AF. It has been suggested that patients be admitted for the initiation of Class I and Class III antiarrhythmic drugs to avoid serious proarrhythmic consequences. The most clinically significant proarrhythmic response to Class IC agents is likely due to an interaction with acute ischemia, and hospitalization for initiation of drug therapy has little predictive or preventive value. Amiodarone has a low risk of proarrhythmia, and any proarrhythmic reactions are generally delayed. Class IA and Class III antiarrhythmic drugs cause acquired long QT syndrome arrhythmias, which can occur soon after initiation of therapy; however, only about half of the arrhythmic events occur within 3 days of initiation of therapy. It could be argued that all patients should be hospitalized to begin Class IA or Class III drugs; however, this approach has a low yield and is extremely expensive. An alternative is to use Class IA and Class III drugs for patients at low risk of torsades de pointes (e.g., males without heart failure, ventricular tachyarrhythmias, or active coronary disease), in whom hospitalization for drug initiation is not warranted. Higher risk patients are probably better treated with other agents, such as Class IC drugs or amiodarone for women without organic heart disease and amiodarone for patients with heart failure, a history of ventricular tachycardia, or active coronary disease. When a Class IA or Class III drug is required for a patient with an increased risk of torsades de pointes, hospital admission for drug initiation may be indicated.
Optimal Target Site for Slow AV Nodal Pathway Ablation
Authors: YAMANE TEIICHI , IESAKA YOSHITO , GOYA MASAHIKO , TAKAHASHI ATSUSHI , FUJIWARA HIDEOMI , HIRAOKA MASAYASU
Published: April 2007

Optimal Target Site for Slow AV Nodal Pathway. Introduction: Although a variety of ablation techniques have been developed in the treatment of atrioventricular nodal reentrant tachycardia (AVNRT), there have been few reports discussing the location of the optimal target site. Based on our early experiences, we hypothesized that radiofrequency (RF) current applied around the upper margin of the coronary sinus ostium (UCSO) results in the most effective and safe treatment of AVNRT.

Methods and Results: To confirm our hypothesis, the efficacy of RF currents applied around the UCSO guided by local electrograms in 59 patients (group B: predetermined focal mapping approach) were compared with the outcomes in 60 other patients previously treated with the standard electrogram‐guided mapping method starting around the lower margin of the coronary sinus ostium (group A). The precise location of ablation catheters at successful sites (S) was also evaluated. All the patients were successfully treated without complications. Significantly fewer RF pulses and lower energies were needed in group B patients (mean RF applications: 4.3 vs 1.4 applications, mean total energy delivered: 4,699 vs 2,236 J in groups A and B, respectively, P < 0.01). Detailed analyses of the anatomical locations of S using CS venography in group B patients who received only a single RF application (46 patients) revealed that the distance between His and S varied according to the length of Koch's triangle, while that between S and UCSO was relatively constant. In 85% of these 46 patients, S was located within 5 mm above and below the level of the UCSO.

Conclusion: RF applications around the UCSO guided by local electrograms yielded excellent outcomes in AVNRT patients with wide varieties in the size of Koch's triangle. The optimal target site was located within 5 mm above and below the level of UCSO along the tricuspid annulus.
Electroanatomic Mapping for Radiofrequency Ablation of Cardiac Arrhythmias
Authors: VARANASI SANKAR , DHALA ANWER , BLANCK ZALMEN , DESHPANDE SANJAY , AKHTAR MASOOD , SRA JASBIR
Published: April 2007

Nonfluoroscopic Mapping for Cardiac Arrhythmias. Radiofrequency catheter ablation is the current treatment of choice for several cardiac arrhythmias. The conventional approach utilizing intracardiac electrograms during sinus rhythm and during tachycardia has inherent limitations including limited two‐dimensional fluoroscopic imaging and the ability to evaluate several potential sites for ablation and to go precisely to the most suitable site. Recently, a nonfluoroscopic three‐dimensional electroanatomic system has been developed for mapping arrhythmias. We describe in this report the advantage of utilizing the system in facilitating a successful outcome in three patients with different arrhythmias.
Alterations in Gene Expression of Proteins Involved in the Calcium Handling in Patients with Atrial Fibrillation
Authors: VAN GELDER ISABELLE C. , BRUNDEL BIANCA J.J.M. , HENNING ROBERT H. , TUINENBURG ANTON E. , TIELEMAN ROBERT G. , DEELMAN LEO , GRANDJEAN JAN G. , DE KAM PIETER JAN , VAN GILST WIEK H. , CRIJNS HARRY J.G.M.
Published: April 2007

Gene Expression in Human Atrial Fibrillation. Introduction: Atrial fibrillation (AF) leads to a loss of atrial contraction within hours to days. During persistence of AF, cellular dedifferentiation and hypertrophy occur, eventually resulting in degenerative changes and cell death. Abnormalities in the calcium handling in response to tachycardia‐induced intracellular calcium overload play a pivotal role in these processes.

Methods and Results: The purpose was to investigate the mRNA expression of proteins and ion channels influencing the calcium handling in patients with persistent AF. Right atrial appendages were obtained from 18 matched controls in sinus rhythm (group 1) and 18 patients with persistent AF undergoing elective cardiac surgery. Previous duration of AF was ≥ 6 months in 9 (group 2) and > 6 months in 9 patients (group 3). In a single semiquantitative polymerase chain reaction, the mRNA of interest and of glyceraldehydes‐3‐phosphate dehydrogenase, were coamplified and separated by gel electrophoresis. L‐type calcium channel α, subunit mRNA content was inversely related to the duration of AF: −26% in group 2 compared to group 1 (P = 0.2), and −49% in group 3 compared to group 1 (P = 0.01). Inhibitory guanine nucleotide binding protein iα2 mRNA content was reduced in group 3 compared to group 1 (−30%, P = 0.01). Sarcoplasmic reticulum calcium ATPase, phospholamban and sodiumcalcium exchanger mRNA contents were not affected by AF.

Conclusions: AF‐induced alterations in mRNA contents of proteins and ion channels involved in the calcium handling seem to occur in relation to the previous duration of AF. In the present patient population, these changes were significant only if AF lasted > 6 months.
Biventricular Shocking Leads Improve Defibrillation Efficacy
Authors: YAMANOUCHI YOSHIO , EFIMOV IGOR R. , MOWREY KENT A. , MAZGALEV TODOR N. , WILKOFF BRUCE L. , TCHOU PATRICK J.
Published: April 2007

Biventricular Shocking Leads:Introduction: A single lead active can configuration has been widely used in patients with life‐threatening ventricular arrhythmias. Occasionally, however, such a defibrillation lead configuration may not achieve adequate defibrillation threshold (DFT). The purpose of this study was to determine whether addition of a left ventricular (LV) lead can improve defibrillation efficacy.

Methods and Results: Three transvenous defibrillation leads (8.3‐French with a 5‐cm long unipolar coil) were placed in the right ventricle (RV), LV, and superior vena cava (SVC), along with an active can (92 cm2) in the left subpectoral area. The DFT stored energy of seven combinations of these defibrillation leads were compared in a pig ventricular fibrillation model using a biphasic defibrillation waveform (125 μF, 6.5/3.5 msec). A biventricular leads active can configuration in which the RV and LV leads were of the same polarity reduced the DFT stored energy by approximately 35% when compared to a single RV lead active can configuration (9.6 ± 3.0 J vs 15.0 ± 7.2 J, respectively, P = 0.02). Moreover, adding a SVC lead further reduced the DFT energy (8.4 ± 3.3 J).

Conclusion: A biventricular leads active can configuration can significantly improve defibrillation efficacy as compared to a single lead active can configuration. In such a defibrillation lead configuration, the polarity of RV and LV leads should be the same.
Quatrefoil Reentry in Myocardinm: An Optical Imaging Study of the Induction Mechanism
Authors: LIN SHIEN‐FONG , ROTH BRADLEY J. , WIKSWO JOHN P.
Published: April 2007

Quatrefoil Reentry in Myocardium. Introduction: The “critical point hypothesis” for induction of ventricular fibrillation has previously been extended to infer the coexistence of four critical points, and hence four simultaneous spiral reentries or a quatrefoil reentry, resulting from only one premature stimulus delivered to the same location as the pacing stimulus. An optical imaging technique was used to explore its existence and to study the induction mechanism of this peculiar reentry pattern.

Methods and Results: In 16 isolated, Langendorff‐perfused rabbit hearts, high‐speed optical imaging at 133 or 267 frames/sec was performed to observe the induced response with a unipolar point electrode. A novel quatrefoil‐shaped reentry pattern consisting of two pairs of opposing rotors was created by delivering long stimuli during the vulnerable phase. Successful induction occurred in a narrow range of coupling intervals. A dogbone pattern of virtual electrodes was established during the premature stimulus. Propagating wavefronts launched from the virtual anodes immediately after the termination of S2. The alternating blocking and conducting effects of the virtual electrodes, as well as the boundary between virtual cathode and virtual anode, provided the necessary pathways for quatrefoil reentry. Propagation directions of the reentrant spiral wavefronts reversed with a reversal in S2 polarity. Quatrefoil reentries were not sustained and lasted 1 to 4 complete cycles.

Conclusion: The initiation of quatrefoil reentry followed anodal‐or cathodal‐break stimulation as a result of local symmetrical enhancement of the dispersion of tissue excitability. The “critical point hypothesis” provides the minimum topology required for this type of reentry; the “graded response hypothesis” can be viewed as providing a more detailed explanation of how this topology is actually realized. Triggering mechanisms due to the “break” mode of stimulation also posits a new mechanism for defibrillation.
Effects of 17β‐Estradiol on Tachycardia‐Induced Changes of Atrial Refractoriness and Cisapride‐Induced Ventricular Arrhythmia
Authors: CHEN YI‐JEN , LEE SHIH‐HUANG , HSIEH MING‐HSIUNG , HSIAO CHIEN‐JU , YU WEN‐CHUNG , CHIOU CHUEN‐WANG , CHEN SHIH‐ANN
Published: April 2007

17β‐Estradiol and Arrhythmia.Introduction: Gender difference is known to be associated with the occurrence of arrhythmia. However, the effects of female sex hormone on atrial electrophysiology, and on the occurrence of torsades de pointes (TdP) induced by cisapride have been unclear.

Methods and Results: Two experiments were included in this study. In experiment 1, effective refractory periods (ERPs) from five epicardial atrial sites were measured before and after rapid atrial pacing at 800 beats/min for 30 minutes in dogs with pretreatment of verapamil (n = 10), 17β‐estradiol (n = 10), or without pretreatment (n = 10, control group). In experiment 2, limb‐lead ECG and monophasic action potentials in the left and right ventricles were recorded before and after each dose of cisapride (2 to 6 mg/kg) during different ventricular rates in dogs with (n = 9) and without (n = 14) concomitant administration of 17β‐estradiol (0.3 μg/kg). After 17β‐estradiol administration, there were greater atrial ERPs in the study dogs than in the control group. The atrial ERPs were shortened significantly after rapid atrial pacing, but the degree was greater in the control group than in the dogs pretreated with verapamil or 17β‐estradiol. Moreover, the recovery of atrial ERPs was faster in dogs pretreated with verapamil or 17βestradiol than in the control group. In experiment 2, cisapride prolonged the QT interval and biventricular APD)90and induced early afterdepolarizations (EADs) in a dose‐dependent manner. However, dogs receiving cisapride combined with 17β‐estradiol had a greater increase of ventricular repolarization and a higher incidence of EADs than those receiving cisapride only. Moreover, dogs receiving cisapride combined with 17β‐estradiol (3/9, 33%) bad a greater incidence of TdP tban those receiving cisapride only (0/14, 0%, P < 0.05).

Conclusions: 17β‐estradiol has a significant effect on atrial electrophysiology, which may be related to the prevention of atrial fibrillation. However, the high incidence of TdP in dogs receiving cisapride combined with 17β‐estradiol suggests that the female sex hormone is an important risk factor of cisapride‐induced proarrhythmia.
Clinical Experience with the New Detection Algorithms for Atrial Fibrillation of a Defibrillator with Dual Chamber Sensing and Pacing
Authors: KÜHLKAMP VOLKER , DÖRNBERGER VOLKER , MEWIS CHRISTIAN , SUCHALLA RALF , BOSCH RALPH E. , SEIPEL LUDGER
Published: April 2007

ICD with DDD Pacemaker. Introduction: A major drawback of therapy with an implantable defibrillator is the nonspecificity of detection. Theoretically, adding atrial sensing information to a decision algorithm could improve specificity of detection.

Methods and Results: This open‐label nonrandomized study compares the detection algorithm of the Ventak AV and the Ventak Mini implantable defibrillators. The Ventak AV (n = 39) uses dual chamber detection as opposed to single chamber detection (with rate stability) in the Ventak Mini (n = 55). Programmed zone configurations, rate thresholds, and stability criteria were identical in all patients. In the Ventak AV group, 235 ventricular tachyarrhythmias were adequately detected and treated by the device. In the Mini group, 699 episodes of ventricular fibrillation/tachycardia occurred. All but six of the latter episodes were correctly identified and treated: one patient with incessant ventricular tachycardia had five episodes not terminated by the device, another episode occurred in a patient with a device/lead defect. In the Ventak AV group, 33 episodes of sinus tachycardia and 166 episodes of atrial fibrillation/flutter activated the device; inappropriate therapy was applied to 41% of atrial fibrillation/flutter episodes. In the Ventak Mini group, 226 supraventricular tachyarrhythmias activated the device, eight of which were sinus tachycardia and 218 were atrial fibrillation or flutter; of the atrial fibrillation/flutter episodes 24% were treated inappropriately (fewer vs Ventak AV, P < 0.001).

Conclusion: The new detection algorithm incorporated in the Ventak AV did not inadvertently withhold therapy for ventricular tachyarrhythmias, but at the same time the number of inappropriate therapies for atrial fibrillation was not decreased in comparison to a single chamber device.
Effects of Multisite Ventricular Pacing on Cardiac Function in Normal Dogs and Dogs with Heart Failure
Authors: FEI LÜ , WROBLESKI DAVID , GROH WILLIAM , VETTER ALISEN , DUFFIN EDWIN G. , ZIPES DOUGLAS P.
Published: April 2007

Multisite Ventricular Pacing in Heart Failure. Introduction: We studied the effects on cardiac function of pacing two right and two left ventricular sites in normal and failing hearts with a normal QRS duration.

Methods and Results: Hemodynamic parameters were studied in isoflurane‐anesthetized dogs with normal hearts and dogs with heart failure induced by rapid ventricular pacing. Unipolar intramyocardial electrodes were placed at the high right atrium and the apex (A) and base (B) of the left (L) and right (R) ventricles (V). Data were collected after pacing for 5 to 20 minutes. In normal dogs, without bundle branch block (BBB), pacing at either the apex or the base of the left ventricle increased cardiac output by approximately 10% compared with right ventricular apex (RVA) pacing with an AV delay of 10 msec. Positive dP/dt increased approximately 10% during four‐site left and right ventricular apex and base (LRVAB) pacing compared with RVA pacing. In dogs with heart failure but without BBB, cardiac output increased by 8.5% (P < 0.01) during four‐site ventricular pacing with AV delays of 0 and 60 msec compared with RVA pacing. Positive dp/dt increased by 23.5% (P < 0.001) with an AV delay of 0 msec and 9.6% (P < 0.001) with an AV delay of 60 msec during LRVAB pacing compared with RVA pacing. His‐bundle pacing was associated with increased cardiac output compared with RVA pacing.

Conclusions: We conclude that pacing simultaneously at two right and two left ventricular sites significantly improves cardiac function compared with single RVA pacing, with or without sequential AV synchrony, in dogs with rapid ventricular pacing‐induced heart failure and no BBB.
Measurement of Funny Current (If) Channel mRNA in Human Atrial Tissue: Correlation with Left Atrial Filling Pressure and Atrial Fibrillation
Authors: LAI LING‐PING , SU MING‐JAI , LIN JIUNN‐LEE , TSAI CHANG‐HER , LIN FANG‐YUE , CHEN YIH‐SHARNG , HWANG JUEY‐JEN , HUANG SHOEI K. STEPHEN , TSENG YUNG‐ZU , LIEN WEN‐PIN
Published: April 2007

If in Human Atrial Tissue. Introduction: The funny current (If) contributes to phase IV spontaneous depolarization in cardiac pacemaker tissue. Enhanced If activity in myocardial tissue may lead to increased automatically and therefore tachyarrhythmia. We measured the amount of If, activity in the messenger ribonucleic acid (mRNA) in human atrial tissue and correlated the mRNA amount to left atrial filling pressure and atrial fibrillation (AF).

Methods and Results: A total of 34 patients undergoing open heart surgery were included (15 men and 19 women, aged 55 ± 10 years). Atrial tissue was obtained from the right atrial free wall, the right atrial appendage, the left atrial free wall, and the left atrial appendage, respectively. The mRNA amount of the If channel was measured by reverse transcription polymerase chain reaction and was normalized to the mRNA levels of glyceraldehyde 3‐phosphate dehydrogenase. We found that the If channel mRNA was present at all the atrial sampling sites. A higher left atrial filling pressure, an indicator of congestive heart failure, was associated with a higher If mRNA level (r2= 0.446, P < 0.01 by linear regression). We also found that the mRNA amount was significantly higher in patients with AF than in patients without AF (1.68 ± 0.49 vs 1.27 ± 0.43; P < 0.05). Age, sex, right atrial filling pressure, left atrial dimension, and left ventricular ejection fraction had no significant effect on the mRNA level.

Conclusion: The nRNA of the If, channel is present in the free‐wall area and appendage area from both atria. Increased left atrial filling pressure and clinical AF are associated with increased If mRNA level.
Characteristics, Circuit, Mechanism, and Ablation of Reentry in the Rabbit Atrioventricular Node
Authors: LIN LI‐JEN , BILLETTE JACQUES , KHALIFE KARIM , MARTEL KARYNE , WANG JUN , MEDKOUR DJAMILA
Published: April 2007

Functional Origin of AV Nodal Reentry. Introduction: The circuitry underlying AV nodal reentry remains debated. We developed a model of AV nodal reentry and assessed the role of nodal inputs, compact node, and its posterior nodal extension (PNE) in this phenomenon.

Methods and Results: A fine scanning of short coupling interval range with an atrial premature heat consistently initiated slow‐fast AV nodal reentrant heats that occurred 37 ± 31 msec (mean ± SD) after His‐bundle activation in 11 of 16 consecutive rabbit heart preparations. The repeated testing (>40 times) of a chosen coupling interval within reentry window (6 ± 9 msec, n = 11) yielded reentrant intervals that varied by 2 ± 1 msec (mean SD for 40 heats ± SD, n = 11). The breakthrough point of reentrant activation, as assessed from four perinodal sites, varied in different preparations from diffuse (4) to anterior (1), medial (3), or posterior (3); mean reentrant interval did not differ between perinodal sites. Antegrade perinodal activation pattern did not differ at reentrant versus nonreentrant coupling intervals and thus was not a primary determinant of reentry. A PNE ablation (n = 4) interrupted the slow pathway conduction and prevented reentry without affecting antegrade perinodal activation or fast pathway conduction.

Conclusion: A reproducible model of AV nodal reentrant beats was developed and used to study underlying circuitry. The AV nodal reentry involves unaltered antegrade perinodal activation, slow PNE conduction and retrograde broad invasion of perinodal tissues starting at a preparation‐dependent breakthrough point. A PNE ablation abolishes the reentry.
Effects of Spatial Segmentation in the Continuous Model of Excitation Propagation in Cardiac Muscle
Authors: WU JIASHIN , ZIPES DOUGLAS P.
Published: April 2007

Spatial Segmentation in the Simulation of Propagation. Introduction: Spatial segmentation is essential for the numerical simulation of excitation propagation in cardiac muscle.

Methods and Results: This study evaluated the effects of spatial segmentation on action potential and on the velocity of propagation in a continuous one‐dimensional model of cardiac muscle [intracellular and extracellular resistivities along (L) and transverse (T) to the muscle fibers: 402 ωcm (Ri, L), 3,620 ωcm (Ri, T), 48 ωcm (Re, L), and 126 ωcm (Re, T), J of Physiol 255:335‐346, 1976) and either Luo‐Rudy (L‐R, Circ Res 68:1501‐1526, 1991) or Beeler‐Reuter (B‐R, J Physiol 268:177‐210, 1977) ionic currents. Related cable equations for active membrane are derived. Spatial segmentations of < 31.2 μm (L, L‐R), < 11.5 μm (T, L‐R), < 44.7 μm (L, B‐R), and < 16.5 μm (T, B‐R) were required for < 1% errors in the characteristic parameters of action potential. Similarly, spatial segmentations of < 54.5 μm (L, L‐R), < 20.1 μm (T, L‐R), < 84.3 μm (L, B‐R), and < 31.2 μm (T, B‐R) were required for < 1% errors in the velocity of conduction.

Conclusion: In general, spatial segmentations of < 26.9% and < 50.8% of the space constant of a fully activated membrane gave < 1.0% errors in the characteristic parameters of action potential and in the velocity of propagation, respectively, for both membranes. The action potential duration was relatively insensitive to the spatial segmentation. Our analysis suggests that λfull is a better criterion for the selection of spatial segmentation in numerical simulation than the space constant of the resting membrane.
Radiofrequency Catheter Ablation of Left Ventricular Outflow Tract Tachycardia from the Coronary Cusp: A New Approach to the Tachycardia Focus
Authors: SHIMOIKE EIMEI , OHNISHI YASUSHI , UEDA NORIHIRO , MARUYAMA TORU , KAJI YOSHIKAZU
Published: April 2007

Transcoronary Cusp Ablation of VT. Introduction: Idiopathic ventricular tachycardia (VT) originating from the left ventricular outflow tract (LVOT) is rare. Previously reported were two cases of LVOT tachycardia which were treated with radiofrequency (RF) catheter ablation through endocardial aortomitral continuity. We report here a case of a repetitive LVOT tachycardia in which the QRS morphology during VT exhibited an atypical left bundle branch block and inferior axis. Pace mapping revealed that the origin of this VT was very close to the left sinus of Valsalva. Transcoronary cusp RF catheter ablation abolished the VT in this patient and is a new approach for the treatment of this kind of VT. The application of this approach to the other types of VT has yet to he determined.
Transient Local Changes in Right Ventricular Monophasic Action Potentials Due to Ajmaline in a Patient with Brugada Syndrome
Authors: ECKARDT LARS , KIRCHHOF PAULUS , JOHNA ROBERT , BREITHARDT GÜNTER , BORGGREFE MARTIN , HAVERKAMP WILHELM
Published: April 2007

Monophasic Action Potential Recording in Brugada Syndrome. A 48‐year‐old patient with recurrent episodes of palpitations and syncope presented with transient ST segment elevation in the right precordial ECG leads. Structural heart disease was excluded. No arrhythmias were inducible by programmed ventricular stimulation. Parallel to ST elevation after intravenous ajmaline, a gradual and reversible delay in the upstroke of right ventricular (RV) monophasic action potentials (MAPs) occurred that was most marked in the RV outflow tract and nearly absent at right free‐wall recordings. Ajmaline led to a cycle length‐dependent increase in RV dispersion of repolarization. Thus, right endocardial MAPs may demonstrate regionally different action potential changes that may contribute to the ECG changes in Brugada syndrome.
Interaction Between Atrial Pacing Lead and Epicardial Ventricular Wire Resulting in Unintended Ventricular Capture by Pacemaker Atrial Output
Authors: Rosenbaum David S. , CHEN PENG‐SHENG
Published: April 2007

A 65‐year‐old man with a history of coronary artery disease underwent coronary artery bypass grafting in 1997 and 1998. He also received a permanent dual chamber pacemaker implantation during the second bypass surgery for complete heart block. He presented a year later to our pacemaker clinic for follow‐up. Initial ECG showed ventricular capture by pacemaker atrial output (bottom tracings, left side). When the atrial output was decreased by 0.5V, normal atrial and ventricular pacemaker function was restored (bottom tracings, right side). A chest X‐ray revealed an active fixation atrial lead implanted to the right atrium and a passive fixation lead to the ventricle. There was no apparent insulation failure of either lead by X‐ray or by impedance measurements. An epicardial pacing lead implanted during bypass surgery for temporary postoperative pacing was not completely removed. The proximity between the retained epicardial wire and the screw of the active fixation atrial lead (arrow) support the hypothesis that the atrial output was conducted by the retained epicardial wire into the ventricles, resulting in unintended ventricular capture by the atrial output. However, we could not exclude the possibility that the atrial lead directly resulted in ventricular capture due to its proximity to the AV grove.
Bimodal RR Interval Distribution in Chronic Atrial Fibrillation:
Authors: TEBBENJOHANNS JÜRGEN , SCHUMACHER BURGHARD , KORTE THOMAS , NIEHAUS MICHAEL , PFEIFFER DIETRICH
Published: April 2007

Bimodal RR Interval Distribution, Introduction: Radiofrequency (RF) catheter modification of the AV node hi patients with atrial fibrillation (AF) is limited by an unpredictable decrease of the ventricular rate and a wish incidence of permanent AV block, A bimodal RR histogram has been suggested to serve as a predictor for successful outcome but the corresponding AV node properties have never been characterized, We hypothesized that a bimodal histogram indicates dual AV nodal physiology and predicts a better outcome after AV node modification in chronic AF.

Methods and Results: Thirty‐seven patients were prospectively subdivided into two groups according to the RR histogram of 24‐hour ECC monitoring, Before to RF ablation, internal cardioversion and programmed stimulation were performed, Among the 22 patients (group I) with a bimodal RR histogram, dual AV nodal physiology was found in 17 (779f) patients, Ablation significantly decreased ventricular rate with loss of the peak of short RR cycles after ablation (mean and maximal ventricular rates: 32% and 35% rate reduction, respectively; P < 0,01), In 15 patients with a unimodal RR histogram (group II), dual AV nodal physiology was found in 2 (13%), and rate reductions were 16% and 17%, respectively, At 6 months, 3 (14%) patients in group 1 and 6 (40%) in group II underwent elective AV nodal ablation with pacemaker implantation due to intolerable rapid ventricular response to AF.

Conclusion: Bimodal RR interval distribution during chronic AF suggests the presence of dual AV nodal physiology and predicts a better outcome of RF ablation of the posterior atrionocdal input.
Cycle Length Dynamics at the Onset of Postinfarction Ventricular Tachycardias Induced in Canines:
Authors: HÉLIE V FRANÇOIS , VINET ALAIN , CARDINAL RENÉ
Published: April 2007

Tachycardia Onset Dynamics. Introduction: Postinfarction monomorphic ventricular tachycardius induced by programmed stimulation may display initial cycle length (CL) variations before stabilizing.

Methods and Results: To show that tachycardia onset dynamics depend on rate‐dependent electrical properties of the reentrant substrate, we extracted activation times and maximum negative slopes of local activation complexes (‐dV/dtmax) from 191 unipolar electrograms recorded in the anterior left ventricular wall of anesthetized, 3‐day‐old infarct canine preparations. Measurements were made of the responses to programmed stimulation, as well as in early and later beats of tachycardias, which displayed either a constant trend in CL (group A, n = 5 preparations) or one in which CL prolongation occurred according to an exponential course before stabilizing (group B, n = 9). Stimulation protocols inducing the tachycardias were more aggressive and their CL was significantly shorter (CL = 159 ± 24 msec) in group A than in group B (stabilized CL = 206 ± 34 msec). Reentrant activity occurred in subepicardial areas in which the absolute value of ‐dV/dtmax (|‐dV/dtmax|) was heterogeneously depressed (<2 mV/msec). |‐dV/dtmax| was reduced and activation delay increased in the successive responses to extrastimuli. Further reductions in |‐dV/dtmax| (10% to 23%) were shown to occur between early and later beats in 5 of the 9 tachycardias in group B (no change in the 4 others), and they were associated with localized prolongation of conduction times in reentrant pathways. In contrast, |‐dV/dtmax| improved in all group A tachycardias (7% to 25%).

Conclusion: This study provides evidence that the onset dynamics of postinfarction ventricular tachycardias are determined by interval‐dependent electrical changes occurring in the reentrant substrate.
Simultaneous Optical Mapping of Transmembrane Potential and Intracellular Calcium in Myocyte Cultures
Authors: FAST VLADIMIR G. , IDEKER RAYMOND E.
Published: April 2007

Simultaneous Mapping of Vm and Cai2+. Introduction: Fast spatially resolved measurements of transmembrane potential (Vm) and intracellular calcium (Cai2+) are important for studying mechanisms of arrhythmias and defibrillation. The goals of this work were (1) to develop an optical technique for simultaneous multisite optical recordings of Vm and Cai2+, and (2) to determine the relationship between Vm and Cai2+ during normal impulse propagation in myocyte cultures.

Methods and Results: Monolayers of neonatal rat myocytes were stained with fluorescent dye RH‐237 (Vm) and Fluo‐3AM (Cai2+). Both dyes were excited at the same wavelength range. The emitted fluorescent was optically separated into components corresponding to changes in Vm, and Cai2+ and measured using two 16 × 16 photodiode arrays at a spatial resolution of up to 27.5 μm per diode and sampling rate of 2.5 kHz. The optical setup was adjusted so that there was no optical cross‐talk between the two types of measurements, which was validated in experiments involving staining with either RH‐237 or Fluo‐3. The amplitude of Fluo‐3 signals rapidly decreased during experiments due to dye leakage. Dye leakage was substantially reduced by application of 1 mM probenecid, a blocker of organic anion transport, which had no effect on action potential duration and only minor effect on conduction velocity. In double‐stained preparations, during regular pacing Cai2+ transients had a rise time of 14.2 ± 2 msec, and they followed Vm upstrokes with a delay of 5.3 ± 1 msec (n = 9). Durations of Vm, and Cai2+ transients determined at 50% level of signal recovery were 54.6 ± 10 msec and 136 ± 8 msec, respectively. Application of 2 μM nifedipine reduced the amplitude and duration of Cai2+ transients without significantly affecting conduction velocity.

Conclusion: The results demonstrate feasibility of simultaneous optical recordings of Vm and Cai2+ transients with high spatial and temporal resolution.