bluuebunny/crossref_metadata_2025 huggingface dataset:
Provoked and Spontaneous High‐Frequency, Low‐Amplitude, Respirophasic Noise Transients in Patients with Implantable Cardioverter Defibrillators
Authors: SWEENEY MICHAEL O. , ELLISON KRISTIN E. , SHEA JULIE B. , NEWELL JOHN B.
Published: August 2003

Respirophasic Noise Transients in ICD Patients. Introduction: Ventricular oversensing (OS) of respirophasic noise transients may cause spurious detections and therapies and pacing inhibition among patients with implantable cardioverter defibrillators (ICDs). The incidence of OS and its relationship to clinical variables and ICD system design are unknown.

Methods and Results: Three hundred twenty‐nine patients performed provocative respiratory maneuvers at rest during intrinsic rhythm and continuous ventricular pacing. OS resulting in spurious ventricular detections was provoked in 3 (0.9%) of 329 patients during intrinsic rhythm and 34 (10.3%) of 329 during pacing. Noise transients not recognized and marked as sensed events, but visually evident on the local endocardial ventricular electrogram, were provoked in an additional 23 (7.0%) of 329 patients. Multivariate logistic regression identified history of spontaneous OS (P < 0.0005, odds ratio 9.7, 95% confidence interval [CI] 1.9 to 50.0), automatic gain control device (P < 0.0005, odds ratio 5.3, 95% CI 2.6 to 10.8) or integrated bipolar lead (P = 0.05, odds ratio 2.6, 95% CI 1.0 to 7.25), and male gender (P = 0.008, odds ratio 3.7, 95% CI 1.2 to 11.1) as predictive of provocable OS. Spontaneous OS resulting in spurious ventricular detections and therapies occurred in 12 (3.6%) patients during follow‐up. Eleven of 12 spontaneous episodes occurred in male patients during ventricular pacing; 11 of 12 patients had automatic gain control devices and integrated bipolar leads.

Conclusion: OS is commonly provoked in ICD patients during ventricular pacing and may occur spontaneously, causing spurious tachyarrhythmia therapies and pacing inhibition. Differences in the incidence of spontaneous and provoked OS between ICD systems can be explained on the basis of unique features of automatic sensing systems and sensing lead design.
Problems of Heart Rate Correction in Assessment of Drug‐Induced QT Interval Prolongation
Authors: MALIK MAREK
Published: August 2003

Problems of Drug‐Prolonged QTc Assessment.
Introduction: Estimation of QT interval prolongation belongs to safety assessment of every drug. Among unresolved issues, heart rate correction of the QT interval may be problematic. This article proposes a strategy for heart rate correction in drug safety studies and demonstrates the strategy using a study of ebastine, a nonsedating antihistamine.

Methods and Results: Four‐way cross‐over Phase I study investigated 32 subjects on placebo, ebastine 60 mg once a day, 100 mg once a day, and terfenadine 180 mg twice a day. Repeated ECGs were obtained before each arm and after 7 days of treatment. The changes in heart rate‐corrected QTc interval were investigated using (A) 20 published heart rate correction formulas, (B) a correction formula optimized by QT/RR regression modeling in all baseline data, and (C) individual corrections optimized for each subject by drug‐free QT/RR regression modeling. (A) Previously published correction formulas found QTc interval increases on terfenadine. The results with ebastine were inconsistent. For instance, Bazett's and Lecocq's correction found significant QTc increase and decrease on ebastine, respectively. The results were related (|r| > 0.95) to the success of each formula (independence of drug‐free QTc and RR intervals). (B) The pooled drug‐free QT/RR regression found an optimized correction QTc = QT/RR0.314. QTc interval changes on placebo, ebastine 60 mg, ebastine 100 mg, and terfenadine were − 1.95 ± 6.87 msec (P = 0.18), − 3.91 ± 9.38 msec (P = 0.053), 0.75 ± 8.23 msec (P = 0.66), and 12.95 ± 14.64 msec (P = 0.00025), respectively. (C) Individual QT/RR regressions were significantly different between subjects and found optimized corrections QTc = QT/RRα with α= 0.161 to 0.417. Individualized QTc interval changes on placebo, ebastine 60 mg, ebastine 100 mg, and terfenadine were − 2.76 ± 5.51 msec (P = 0.022), − 3.15 ± 9.17 msec (P = 0.11), − 2.61 ± 9.55 msec (P = 0.19), and 12.43 ± 15.25 msec (P = 0.00057), respectively. Drug‐unrelated QTc changes up to 4.70 ± 8.92 msec reflected measurement variability.

Conclusion: Use of published heart rate correction formulas in the assessment of drug‐induced QTc prolongation is inappropriate, especially when the drug might induce heart rate changes. Correction formulas optimized for pooled drug‐free data are inferior to the formulas individualized for each subject. Measurement imprecision and natural variability can lead to mean QTc interval changes of 4 to 5 msec in the absence of drug treatment.
T Wave Alternans Threshold in Normal Children
Authors: CHEUNG MICHAEL M.H. , DAVIS ANDREW M. , COHEN RICHARD J. , WILKINSON JAMES L.
Published: August 2003

T Wave Alternans in Children.
Introduction: Sustained microvolt‐level T wave alternans (TWA) during exercise is a predictor of ventricular arrhythmia propensity in adult populations. TWA occurs in normal adults, but it is rare at < 70% of predicted maximum heart rate. An onset heart rate ≤ 110 is believed to be significant. The aim of this study was to examine the feasibility of performing the test in children and to determine the normal heart rate threshold for sustained TWA in children.

Methods and Results: Alternans was evaluated during bicycle exercise in 100 normal volunteers aged 8 to 17 years. Adequate resting data were obtained in 76 of 100 children and was negative in all. Exercise data from 16 of 100 was excluded due to excessive noise. Median maximum heart rate was 192 (range 140 to 214). Sustained alternans was absent in 75 (89%) of 84. In the nine children with sustained alternans, median onset heart rate was 138 (range 120 to 158), and 7 of 9 had an onset heart rate ≤ 135. Median heart rate threshold as a percentage of predicted maximum heart rate (220 – age) was 67% (range 58% to 76%). Only 1 subject (1.2%) had an onset heart rate < 60% of predicted maximum. There was no significant difference between age, gender, endurance, maximum heart rate, QRS duration, QT interval, or QTc in those with and those without sustained TWA.

Conclusion: Noninvasive assessment of TWA is feasible at ≤ 8 years of age. Sustained TWA was present in 11% of normal children, but was absent at heart rates below 120 and rare (1.2%) below 60% of predicted maximum heart rate.
Diagnosis of Amiodarone Pulmonary Toxicity with HighResolution Computerized Tomographic Scan
Authors: SINIAKOWICZ ROBERT M. , NARULA DHIRAJ , SUSTER BERNARD , STEINBERG JONATHAN S.
Published: August 2003

Chest CT and Amiodarone Pulmonary Toxicity.
Introduction: Amiodarone pulmonary toxicity is a serious adverse effect that can be fatal. The diagnosis is difficult due to the nonspecificity of symptoms, clinical findings, and test results. Because of its high iodine content, amiodarone deposition can be detected by sensitive high‐resolution computed tomographic (CT) scan techniques. We hypothesized that pulmonary toxicity can be diagnosed more readily when these scans indicate the presence of increased attenuation of either pleural or pulmonary densities representing high iodine amiodarone deposits.

Methods and Results: This case control study included 16 patients taking chronic amiodarone. Eight cases presented with severe respiratory and other symptoms and were matched with 8 controls, 4 with mild or chronic respiratory symptoms. All patients underwent high‐resolution CT of the chest. All cases had positive CT scan results demonstrating bilateral air‐space disease, parenchymal bands, and thickened septal and bronchiolitis obliterans. All minimally or asymptomatic patients had negative scans with no area of high attenuation. All cases had ≤ 1 lesion with high‐attenuation density. The cases were treated successfully by supportive care, discontinuation of amiodarone, and, rarely, corticosteroid therapy. Two cases had delayed diagnosis of amiodarone pulmonary toxicity and were managed successfully only ter CT.

Conclusion: High‐resolution CT may be a valuable noninvasive test to aid in the diagnosis of amiodarone pulmonary toxicity in symptomatic patients.
Catheter Cryoablation of the Atrioventricular Node in Patients with Atrial Fibrillation: A Novel Technology for Ablation of Cardiac Arrhythmias
Authors: DUBUC MARC , KHAIRY PAUL , RODRIGUEZ‐SANTIAGO ANGEL , TALAJIC MARIO , TARDIF JEAN‐CLAUDE , THIBAULT BERNARD , ROY DENIS
Published: August 2003

Percutaneous Catheter Cryoablation in Man.
Introduction: Recent animal studies demonstrated the feasibility and safety of applying percutaneous catheter cryoablation technology for ablation of arrhythmogenic sites. The studies also showed that reversible “ice mapping” can be performed before creating permanent lesions. We investigated the feasibility and safety of applying this new technology in man.

Methods and Results: Cryoablation of the AV node (AVN) using a 9‐French quadripolar catheter with a 4‐mm electrode tip was attempted in 12 patients (mean age 67.8 ± 11.4 years) with refractory atrial fibrillation. Whereas technical issues prevented adequate tissue contact in two patients, complete AVN block was obtained in the remaining 10 patients after 4.8 ± 1.9 cryoapplications lasting 5.5 ± 0.2 minutes resulting in temperatures of −58.1°± 5.4°C. In all patients with sinus rhythm at the time of the procedure, cryomapping at warmer temperatures induced reversible AVN block and allowed confirmation of a successful site before definitive ablation. Intracardiac echocardiography was performed in three patients and allowed visualization of the cryocatheter‐endocardial contact and cryolesion formation. No major procedural complications were reported. After 6 months of follow‐up, 8 of 10 initially successful patients remained in complete block; 1 had partial recovery of AVN conduction manifested by atrial fibrillation with a slow ventricular response, and 1 fully recovered AVN conduction.

Conclusion: (1) Catheter cryoablation of the AVN can be performed safely in man. (2) Reversible cryomapping is feasible and may offer an advantage over radiofrequency ablation. (3) Cryocatheterendocardial contact and cryolesion growth can be monitored with intracardiac echocardiography.
Ventricular Fibrillation Sensing and Detection by Implantable Defibrillators: Is One Better than the Others? A Prospective, Comparative Study
Authors: PANOTOPOULOS PANOGIOTIS , KRUM DAVID , AXTELL KATHI , DHALA ANWER , SRA JASBIR , AKHTAR MASOOD , DESHPANDE SANJAY
Published: August 2003

ICD Sensing During VF.
Introduction: We prospectively compared the performance of the sensing and detection systems of three leading defibrillator manufacturers: Medtronic, Guidant, and Ventritex.

Methods and Results: Ventricular fibrillation signal was digitally recorded during defibrillator implantation and subsequently played back sequentially to a Medtronic Micro Jewel II 7223Cx, a Guidant MINI II 1762, and a Ventritex Cadet V‐115C. The devices were programmed for single‐zone detection, at nominal settings. Rate cutoff was set at 320 msec (185/min for the MINI). We analyzed 253 episodes from 47 patients. Median undersensing was 0%, 2.1%, and 5.3% for the Jewel, MINI, and Cadet, respectively (P < 0.001 for each paired comparison). Detection time was 4.1 ± 1.6 seconds, 3.4 ± 1.6 seconds, and 4.3 ± 2.2 seconds for the Jewel, MINI, and Cadet, respectively (P < 0.001 between MINI‐Jewel and MINI– Cadet; P < 0.01 between Jewel‐Cadet). Delayed detection (detection time longer than the mean of all observations + 2 SD) occurred in 3 (1.2%), 7 (2.8%), and 18 (7.1%) episodes for the Jewel, MINI, and Cadet, respectively. Performance for all devices was worse when the short‐separation integrated bipolar lead was used and when the episode followed a failed high‐energy shock.

Conclusion: Statistically significant differences were seen in sensing and detection performance among the devices and device/lead combinations during ventricular fibrillation. These differences are related to specific features of the respective devices and should be taken into account during clinical practice, as well as in future device development.
Electrocardiographic Prediction of Abnormal Genotype in Congenital Long QT Syndrome: Experience in 101 Related Family Members
Authors: KAUFMAN ELIZABETH S. , PRIORI SILVIA G. , NAPOLITANO CARLO , SCHWARTZ PETER J. , IYENGAR SUDHA , ELSTON ROBERT C. , SCHNELL AUDREY H. , GORODESKI EIRAN Z. , RAMMOHAN GUHAN , BAHHUR NAEL O. , CONNUCK DAVID , VERRILLI LINDA , ROSENBAUM DAVID S. , BROWN ARTHUR M.
Published: August 2003

Prediction of Congenital Long QT Syndrome.
Introduction: Previous studies showed that diagnosing congenital long QT syndrome (LQTS) is difficult due to variable penetrance and genetic heterogeneity, especially when subjects from multiple families with diverse mutations are combined. We hypothesized that a combination of clinical and ECG techniques could identify gene carriers within a single family with congenital LQTS.

Methods and Results: One hundred one genotyped members of a family with LQTS, including 26 carriers of a HERG mutation, underwent history and ECG analysis. Forty‐eight family members also underwent exercise testing with QT and T wave alternans (TWA) analysis and 24‐hour Holter monitoring with QT and heart rate variability analysis. A logistic regression model, which included age, gender, QTc, and QTc by age, provided the best prediction of gene carrier status, although there was substantial overlap (78%) of QTc among subjects with and without the mutation. QTc was not helpful as a discriminator in children ≤ 13 years. TWA (observed infrequently) did not add significantly to the model's ability to predict abnormal genotype.

Conclusion: Even in this homogeneous LQTS population, the phenotype was so variable that clinical and detailed ECG analyses did not permit an accurate diagnosis of gene carrier status, especially in children. Sustained microvolt TWA was a specific (100%) but insensitive (18%) marker for LQTS. Its ability to predict risk of arrhythmia in this population remains to be determined. Genetic testing serves an essential role in screening for carriers of LQTS.
Reduction in Atrial Defibrillation Threshold by a Single Linear Ablation Lesion
Authors: WHITE JAMES B. , FOTUHI PARWIS C. , PEDOTO RAMON W. , CHATTIPAKORN NIPON , ROGERS JACK M. , IDEKER RAYMOND E.
Published: August 2003

Single Lesion Lowers ADFT.
Introduction: This study investigated a hybrid approach to reduce the atrial defibrillation threshold (ADFT) by determining the effect of a single linear radiofrequency ablation (RFA) lesion on both the ADFT and activation patterns during atrial fibrillation (AF).

Methods and Results: In 18 open chest sheep (45 to 57 kg), coil defibrillation electrodes were placed in a superior vena cava/right ventricular configuration. AF was induced by burst pacing and maintained with acetyl β‐methylcholine (2 to 42 μL/min). ADFTs were obtained before and after a linear RFA lesion was created in the left atrium (LAL; n = 6), right atrium (RAL; n = 6), or neither atrium as a control (n = 6). In animals receiving an LAL, a 504‐unipolar‐electrode plaque was sutured to the LA. For animals receiving an RAL, two 504‐electrode plaques were placed, one each on the LA and RA. From each plaque, activations were recorded before and after ADFT shocks, and organizational characteristics of activations were analyzed using algorithms that track individual wavefronts. In sham‐treated controls, the ADFT did not change. In contrast, LAL reduced ADFT energy 29%, from 4.5 ± 2.3 J to 3.2 ± 2.0 J (P < 0.05). RAL reduced ADFT energy 25%, from 2.0 ± 0.9 J to 1.5 ± 0.7 J (P < 0.05). AF activation was substantially more organized after RFA than before RFA for both the RAL‐ and LAL‐treated animals.

Conclusion: A single RFA lesion in either the RA or LA reduces the ADFT in this sheep model. This decrease is associated with an increase in fibrillatory organization.
Chromanol 293B Inhibits Slowly Activating Delayed Rectifier and Transient Outward Currents in Canine Left Ventricular Myocytes
Authors: SUN ZHUO‐QIAN , THOMAS GEORGE P. , ANTZELEVITCH CHARLES
Published: August 2003

Chromanol 293B on Ionic Currents.
Introduction: Drugs that selectively inhibit the slowly activating component of the delayed rectifier potassium current (IKs) are being considered as possible antiarrhythmic agents, because they produce more prolongation of action potential duration at fast rates with less transmural dispersion of repolarization compared with blockers of the rapidly activating component (IKr). Although the chromanol derivative chromanol 293B has been shown to be relatively selective in blocking IKs in some species, its selectivity is far from established.

Methods and Results: The present study uses whole‐cell, patch‐clamp technique to examine the selectivity of this compound for inhibition of IKs in comparison with other repolarizing ionic currents, such as IKr, inward rectifier potassium current (IK1), transient outward current (Ito), and L‐type calcium current (ICa‐L) in canine left ventricular mid‐myocardial and endocardial cells. Chromanol 293B blocked IKs with an IC50 of 1.8 μM and Ito with an IC50 of 38 μM. Concentrations as high as 30 μM did not affect IK1, IKr, or ICa‐L. Higher concentrations of chromanol 293B (100 μM) caused a slight, but statistically insignificant, inhibition of IKr.

Conclusion: Our results indicate that chromanol 293B is a relatively selective blocker of IKs in canine left ventricular myocytes.
Properties and Substrate of Slow Pathway Exposed with a Compact Node Targeted Fast Pathway Ablation in Rabbit Atrioventricular Node
Authors: LIN LI‐JEN , BILLETTE JACQUES , MEDKOUR DJAMILA , REID MARIE CLAUDE , TREMBLAY MAURICE , KHALIFE KARIM
Published: August 2003

Selective Slow Nodal Pathway Model.
Introduction: The properties and substrates of slow and fast AV nodal pathway remain unclear. This applies particularly to the slow pathway (SP), which is largely concealed by fast pathway (FP) conduction. We designed a new FP ablation approach that exposes the SP over the entire cycle length range and allows for its independent characterization and ablation.

Methods and Results: Premature stimulation was performed before and after FP ablation with 5.4 ± 1.9 lesions (300‐μm diameter each; overall lesion size 1.4 ± 0.5 mm) targeting the junction between perinodal and compact node tissues in seven rabbit heart preparations. The resulting SP recovery curve and control curve had the same maximum nodal conduction time (165 ± 22 msec vs 164 ± 24 msec; P = NS) and effective refractory period (101 ± 10 msec vs 100 ± 9 msec; P = NS). The two curves covered the same cycle length range. However, the SP curve was shifted up with respect to control one at intermediate and long cycle lengths and thus showed a longer minimum nodal conduction time (81 ± 15 msec vs 66 ± 10 msec; P < 0.01) and functional refractory period (180 ± 11 msec vs 170 ± 12 msec; P < 0.05). The SP curve was continuous and closely fitted by a single exponential function. Small local lesions (2 ± 1) applied to the posterior nodal extension resulted in third‐degree nodal block in all preparations.

Conclusion: The posterior nodal extension can sustain effective atrial‐His conduction at all cycle lengths and account for both the manifest and concealed portion of SP. Slow and FP conduction primarily arise from the posterior extension and compact node, respectively.
Decremental Atriofascicular Accessory Pathway with Bidirectional Conduction: Delineation of Atrial and Ventricular Insertion by Radiofrequency Current Application
Authors: PEINADO RAFAEL , MERINO JOSE LUIS , RAMÍREZ LEONARDO , ECHEVERRÍA IGNACIO
Published: August 2003

Decremental Atriofascicular Pathway with Bidirectional Conduction. A 17‐year‐old girl with a corrected complex congenital heart disease and recurrent episodes of supraventricular tachycardia was referred for catheter ablation. Electrophysiologic studies revealed the presence of an accessory pathway (AP) with bidirectional conduction and decremental properties. We demonstrated a course parallel to the node‐His AV conduction system. Transient abolition of the bidirectional conduction through the AP was obtained by radiofrequency application to the ventricular insertion located in the distal right bundle branch and to the atrial insertion, located in the mid‐anterior atrial septum. Radiofrequency application at the low anterior atrial septum, above the His bundle, successfully abolished AP conduction without affecting AV nodal conduction. Demonstration of the course and insertions of the AP, its bidirectional decremental conduction properties, and the association with a complex congenital heart disease are exceptional and interesting findings and raise the possibility of an accessory AV node with a parallel conduction pathway to the right bundle branch.
Intravenous Administration of Class I Antiarrhythmic Drugs Induced T Wave Alternans in a Patient with Brugada Syndrome
Authors: CHINUSHI MASAOMI , WASHIZUKA TAKASHI , OKUMURA HIROSHI , AIZAWA YOSHIFUSA
Published: August 2003

T Wave Alternans in Brugada Syndrome. A 71‐year‐old man who experienced aborted sudden death was referred to our hospital. Coronary artery disease and cerebral accident were ruled out by conventional tests. The 12‐lead ECG obtained at rest showed a right bundle branch block pattern and ST segment elevation in leads V1 to V3. Double ventricular extrastimuli at coupling intervals > 180 msec induced ventricular fibrillation (VF) twice during electrophysiologic study. Intravenous administration of procainamide accentuated ST segment elevation in leads V1 to V3, and visible T wave alternans was induced in leads V2 and V3 at a dose of 450 mg. Initiation of T wave alternans was not associated with changes of the cardiac cycle or development of premature beats. When procainamide infusion was discontinued, T wave alternans disappeared before the elevated ST segment returned to the control level. Pilsicainide also accentuated ST segment elevation and induced similar T wave alternans in leads V2 and V3. Class I antiarrhythmic drug‐related T wave alternans has been reported rarely in Brugada syndrome, but it may represent enhanced arrhythmogenicity of VF. We need to monitor closely and study the clinical implications of T wave alternans in Brugada syndrome.
Arrhythmogenesis in Heart Failure
Authors: JANSE MICHIEL J. , VERMEULEN JESSICA T. , OPTHOF TOBIAS , CORONEL RUBEN , WILMS‐SCHOPMAN FRANCIEN J. G. , RADEMAKER HAN M. E. , BAARTSCHEER ANTONIUS , DEKKER LUKAS R. C.
Published: August 2003

Arrhythmogenesis in Heart Failure. In a rabbit model of heart failure produced by combined pressure and volume overload, nonsustained ventricular tachycardias developed in 15 of 23 failing rabbits. Sinus rate was increased in rabbits dying suddenly, but was decreased in survivors. This also was true in isolated preparations. Microelectrode recordings from ventricular trabeculae both from patients with end‐stage failure and from failing rabbits showed that in half of the preparations, delayed afterdepolarizations and triggered activity occurred, but only in the presence of norepinephrine and a lowered extracellular K+ concentration of 3 mM. This was due to spontaneous release of Ca2+ from the sarcoplasmic reticulum.
Incidence and Clinical Significance of Inducible Atrial Tachycardia in Patients with Atrioventricular Nodal Reentrant Tachycardia
Authors: STICHERLING CHRISTIAN , TADA HIROSHI , GREENSTEIN RADMIRA , CHAN CHI‐WO , CHOUGH STEVEN P. , BAKER ROBERT L. , WASMER KRISTINA , ORAL HAKAN , PELOSI FRANK , KNIGHT BRADLEY P. , STRICKBERGER S. ADAM , MORADY FRED
Published: August 2003

Significance of Atrial Tachycardia.
Introduction: The purpose of this prospective study was to determine the prevalence and clinical significance of inducible atrial tachycardia in patients undergoing slow pathway ablation for AV nodal reentrant tachycardia who did not have clinically documented episodes of atrial tachycardia.

Methods and Results: Twenty‐seven (15%) of 176 consecutive patients who underwent slow pathway ablation for AV nodal reentrant tachycardia were found to have inducible atrial tachycardia with a mean cycle length of 351 ± 95 msec. The atrial tachycardia was sustained in 7 (26%) of 27 patients and was isoproterenol dependent in 20 patients (74%). The atrial tachycardia was not ablated or treated with medications, and the patients were followed for 9.7 ± 5.8 months. Six (22%) of the 27 patients experienced recurrent palpitations during follow‐up. In one patient each, the palpitations were found to be due to sustained atrial tachycardia, nonsustained atrial tachycardia, recurrence of AV nodal reentrant tachycardia, paroxysmal atrial fibrillation, sinus tachycardia, and frequent atrial premature depolarizations. Thus, only 2 (7%) of 27 patients with inducible atrial tachycardia later developed symptoms attributable to atrial tachycardia.

Conclusion: Atrial tachycardia may be induced by atrial pacing in 15% of patients with AV nodal reentrant tachycardia. Because the vast majority of patients do not experience symptomatic atrial tachycardia during follow‐up, treatment for atrial tachycardia should be deferred and limited to the occasional patient who later develops symptomatic atrial tachycardia.
Clinical Usefulness of a Multielectrode Basket Catheter for Idiopathic Ventricular Tachycardia Originating from Right Ventricular Outflow Tract
Authors: AIBA TAKESHI , SHIMIZU WATARU , TAGUCHI ATSUSHI , SUYAMA KAZUHIRO , KURITA TAKASHI , AIHARA NAOHIKO , KAMAKURA SHIRO
Published: August 2003

Basket Catheter in Idiopathic VT.
Introduction: It often is difficult to determine the optimal ablation site for idiopathic ventricular tachycardia (VT) originating from the right ventricular outflow tract (RVOT) when the VT or premature ventricular complex (PVC) does not occur frequently. The aim of our study was to evaluate the usefulness of a multielectrode basket catheter for ablation of idiopathic VT originating from the RVOT.

Methods and Results: Radiofrequency (RF) catheter ablation was performed using a 4‐mm tip, quadripolar catheter in 50 consecutive patients with 81 VTs originating from the RVOT with (basket group = 25 patients with 45 VTs) or without (control group = 25 patients with 36 VTs) predeployment of a multielectrode basket catheter composed of 64 electrodes. Deployment of the multielectrode basket catheter was possible and safe in all 25 patients in the basket group. Ablation was successful in 25 (100%) of 25 patients in the basket group and in 22 (88%) of 25 patients in the control group. The total number of RF applications and the number of RF applications per PVC morphology did not differ between the two groups. However, both the fluoroscopic and ablation procedure times per PVC morphology were shorter in the basket group than in the control group (36.8 ± 14.1 min vs 52.0 ± 32.5 min, P = 0.04; 60.0 ± 14.6 vs 81.5 ± 51.2 min, P = 0.05). This difference was more pronounced in the 29 patients in whom VT or PVC was not frequently observed.

Conclusion: The multielectrode basket catheter is safe and useful for determining the optimal ablation site in patients with idiopathic VT originating from the RVOT, especially in those without frequent VT or PVC.
Worldwide Clinical Experience with a New Dual‐Chamber Implantable Cardioverter Defibrillator System
Authors: SCHOELS WOLFGANG , SWERDLOW CHARLES D. , JUNG WERNER , STEIN KENNETH M. , SEIDL KARLHEINZ , HAFFAJEE CHARLES J.
Published: August 2003

New Dual‐Chamber ICD.
Introduction: Management of atrial tachyarrhythmias represents a significant challenge in patients with implantable cardioverter defibrillators (ICDs). Drug therapy of these arrhythmias is limited by moderate efficacy, ventricular proarrhythmia, and drug‐device interactions. This study tested the safety and efficacy of a new dual‐chamber ICD to detect and treat atrial as well as ventricular tachyarrhythmias.

Methods and Results: A dual‐chamber ICD (Medtronic 7250 Jewel AF) was implanted in 293 of 303 patients at 49 centers in Europe, Canada, and North America. Specific data were collected at implant and during a mean follow‐up period of 7.9 ± 4.7 months. There were no clinically evident failures to detect and treat ventricular arrhythmias. In patients with at least one of the dual‐chamber detection criteria activated, 1,056 of 1,192 episodes of ventricular tachycardia or fibrillation detected were judged to be appropriate (89% positive predictive accuracy). Therapy efficacy was 100% in the ventricular fibrillation zone and 98% in the ventricular tachycardia zone. Positive predictive accuracy for detection of atrial episodes was 95% (1,052/1,107). For episodes classified as atrial tachycardia by the device, the efficacy of atrial antitachycardia pacing and high‐frequency (50‐Hz) burst pacing was 55% and 17%, respectively. High‐frequency burst pacing terminated 16.8% of episodes classified as atrial fibrillation, and atrial defibrillation had an estimated efficacy of 76%. The actuarial estimates of 6‐month complication‐free survival and total survival were 88% and 94%, respectively.

Conclusion: This novel dual‐chamber ICD is capable of safely and effectively discriminating atrial from ventricular tachyarrhythmias and of treating atrial tachyarrhythmias without compromising detection and treatment of ventricular tachyarrhythmias.
Radiofrequency Catheter Ablation of Idiopathic Left Ventricular Outflow Tract Tachycardia: Utility of Intracardiac Echocardiography
Authors: LAMBERTI FILIPPO , CALO' LEONARDO , PANDOZI CLAUDIO , CASTRO ANTONIO , LORICCHIO MARIA LUISA , BOGGI AUGUSTO , TOSCANO SALVATORE , RICCI RENATO , DRAGO FABRIZIO , SANTINI MASSIMO
Published: August 2003

Idiopathic LVOT Tachycardia.
Introduction: The site of origin of idiopathic ventricular tachycardia (VT) arising from the left ventricular outflow tract (LVOT) may be closely related to the aortic valve leaflets, and radiofrequency (RF) delivery potentially can damage them. Intracardiac echocardiography (ICE) can identify accurately the ablation electrode and anatomic landmarks, and contact with the endocardium can be easily assessed. The aim of this study was to define the utility and the accuracy of ICE in guiding RF ablation of idiopathic VT of the LVOT.

Methods and Results: Five consecutive patients (all men; mean age 20.4 years, range 16 to 25) symptomatic for idiopathic VT underwent RF ablation. A 9‐French, in‐sheath catheter with a 9‐MHz ultrasound transducer was inserted through the femoral vein and positioned in the His‐bundle region or right ventricular outflow tract to provide a clear view of the aortic root. Local earliest ventricular activation during tachycardia and pace mapping were used to identify the ablation site. Idiopathic VT was ablated successfully in all patients using a median of two RF pulses, delivered during tachycardia. High‐resolution images of the aortic valve and ablation electrode were achievable in all cases. Direct vision of ablation electrode‐endocardial contact in the outflow tract was assessed easily in all patients.

Conclusion: Idiopathic VT of the LVOT can be treated successfully with RF ablation. ICE can accurately guide catheter ablation and identify anatomic landmarks, endocardial contact, and ablation electrode movement.
Female Gender is a Risk Factor for Drug‐Induced Long QT and Cardiac Arrhythmias in an In Vivo Rabbit Model
Authors: LU HUA RONG , REMEYSEN PAUL , SOMERS KATRIEN , SAELS AN , DE CLERCK FRED
Published: August 2003

Gender Differences in Drug‐Induced LQT and TdP.
Introduction: Clinical observations and in vitro experimental data indicate that females have a longer QT interval than males, which is associated with a higher risk of drug‐induced cardiac arrhythmias. Little is known about this gender difference in anesthetized animals, which may affect the outcome of in vivo drug tests.

Methods and Results: We evaluated potential gender differences in ventricular repolarization (QT, QTc, JT, and JTc interval) and its dispersion, as well as in its response to dofetilide, an IKr blocker, in anesthetized rabbits challenged with the α1‐adrenoceptor agonist methoxamine. A 12‐lead ECG was recorded during the experiments. At baseline, there were no significant gender differences in ventricular repolarization values in male and female rabbits under anesthesia. Dofetilide (0.04 mg/kg/min IV for 60 min; n = 10 per gender) produced marked prolongation of the ventricular repolarization time and its dispersion, associated with a high incidence of polymorphic ventricular tachycardia (PVT; 100% in females vs 80% in males) and ventricular fibrillation (VF; 80% in females vs 50% in males; P > 0.05). QT and JT interval at 2 minutes as well as QT and JT dispersion at 10 and 30 minutes during dofetilide infusion were significantly higher in female than in male rabbits. After 30 minutes of dofetilide infusion, 10 of 10 female rabbits had severe cardiac arrhythmias (complete AV block, PVT, or VF), so ECG parameters were impossible to assess (vs 3/10 males with severe cardiac arrhythmias; P < 0.05). During dofetilide infusion, female rabbits developed complete AV block, PVT, or VF at doses about 50% lower than those given to males.

Conclusion: The present study indicates that female rabbits are more susceptible to drug‐induced long QT and cardiac arrhythmias than are male rabbits; therefore, female rabbits are more appropriate for testing drug‐induced cardiac arrhythmias.
Method for Simultaneous Epicardial and Endocardial Mapping of In Vivo Canine Heart: Application to Atrial Conduction Properties and Arrhythmia Mechanisms
Authors: DERAKHCHAN KATAYOUN , LI DANSHI , COURTEMANCHE MARC , SMITH BENJAMIN , BROUILLETTE JUDITH , PAGÉ PIERRE L. , NATTEL STANLEY
Published: August 2003

Endocardial/Epicardial Mapping of AF.
Introduction: It has been suggested that the three‐dimensional structure of the atria may be crucial in arrhythmogenesis; however, previous in vivo atrial activation mapping studies have been limited to either endocardial or epicardial approaches.

Methods and Results: To investigate the role of endocardial and epicardial structures and their interaction in atrial conduction and arrhythmias, we used five epicardial plaques and two intra‐atrial balloon arrays to record a total of 368 unipolar electrograms from the entire epicardial and endocardial surface of both atria. During regular 1:1 pacing from the right atrial appendage, right atrial endocardial activation spread considerably faster than epicardial (total activation time 45 ± 12 msec vs 60 ± 19 msec, respectively [mean ± SD]; P < 0.05), pointing to preferential conduction over structures like the crista terminalis and pectinate muscles. No such differences were noted in the left atrium. Transseptal spread occurred via discrete anterior and posterior pathways, causing separate breakthroughs in anterior and posterior atrial regions, respectively. Dissociation between septal pathways played a role in reentry during vagal atrial fibrillation. In 2 of 4 dogs with atrial fibrillation associated with congestive heart failure, single macroreentrant circuits involving endocardial and epicardial components were revealed during the arrhythmia.

Conclusion: We conclude that activation mapping using simultaneous recording from both epicardial and endocardial surfaces provides potentially important insights into the mechanisms of atrial conduction and arrhythmogenesis.
Critically Timed Auxiliary Shock to Weak Field Area Lowers Defibrillation Threshold
Authors: WALKER ROBERT G. , KENKNIGHT BRUCE H. , IDEKER RAYMOND E.
Published: August 2003

Auxiliary Shock Improves Defibrillation.
Introduction: This study tested the hypothesis that the defibrillation threshold (DFT) can be lowered by delivering a weak auxiliary shock in conjunction with a stronger primary shock to the cardiac region where the primary shock electric field is weakest.

Methods and Results: Eight swine were studied in each of two study parts. In both parts, DFTs were determined for dual shocks delivered through two electrode pairs. The biphasic primary shock was delivered through electrodes in the right ventricle and superior vena cava. The auxiliary shock was delivered through a separate electrode in the superior vena cava and a left ventricular electrode placed where the primary shock field was presumed to be weakest. In part I, a monophasic auxiliary shock of 50, 100, or 150 V was delivered either simultaneously with or 1, 20, or 40 msec before primary shock. When auxiliary shock was delivered simultaneously with or 1 msec before primary shock, DFT energy was reduced by approximately 50% compared with primary shock alone. In part II, a 150‐V monophasic or biphasic auxiliary shock of either polarity was delivered 1 msec before or after primary shock. Regardless of waveform or polarity, all auxiliary shock delivered before primary shock lowered DFT energy by approximately 30% compared with primary shock alone. Depending on waveform and polarity, auxiliary shock delivered after primary shock either did not significantly change the DFT or elevated the DFT compared with primary shock alone.

Conclusion: Application of a small auxiliary shock, just before or simultaneously with a primary shock, to the cardiac region where the primary shock field is weakest significantly lowers DFT.
Role of Calcium in Acute Hyperthermic Myocardial Injury
Authors: EVERETT THOMAS H. , NATH SUNIL , LYNCH CARL , BEACH JAMES M. , WHAYNE JAMES G. , HAINES DAVID E.
Published: August 2003

Hyperthermic Myocardial Injury.
Introduction: We hypothesized that intracellular calcium overload may play an important role in heat‐induced myocardial injury. This postulate was investigated using a model of isolated guinea pig papillary muscle in which resting tension was measured as an indirect indicator of cytosolic free‐calcium concentration and the fluorescence changes of Fluo‐3 AM dye was measured as a direct indicator of cytosolic free‐calcium concentration.

Methods and Results: Excised guinea pig right ventricular papillary muscles were attached to a force transducer in a high‐flow tissue bath and superfused with Tyrode's solution at 37°± 0.5°C. The temperature was rapidly changed to between 38.0° and 56.0°C for 60 seconds and then returned to 37.0°C. Hyperthermia caused a reversible increase in resting tension at temperatures between 45° and 50°C and irreversible contracture at ≥50°C. Rapid cooling contracture experiments and experiments measuring fluorescence of myocytes loaded with 5 μ M Fluo‐3 AM dye demonstrated that the hyperthermia‐induced rise in resting tension was likely due to an increase in intracellular calcium content. Inhibition of the sarcoplasmic reticulum calcium pump with 20 μ M thapsigargin resulted in irreversible contracture of the papillary muscles at temperatures between 45° and 50°C and significant increases in Fluo‐3 fluorescence at 48°C. Blockade of sarcolemmal calcium channels with 0.5 mM cadmium or 40 μ M verapamil did not attenuate the heat‐induced increase in resting tension and Fluo‐3 fluorescence.

Conclusion: Hyperthermia causes an increase in resting tension of cardiac muscle that most likely is mediated by a calcium channel‐independent increase in calcium permeability of the sarcolemmal membrane and/or release of stored intracellular calcium.
Altering Ventricular Activation Remodels Gap Junction Distribution in Canine Heart
Authors: PATEL PRAVINA M. , PLOTNIKOV ALEXEI , KANAGARATNAM PRAPA , SHVILKIN ALEXEI , SHEEHAN CATHERINE T. , XIONG WEN , DANILO PETER , ROSEN MICHAEL R. , PETERS NICHOLAS S.
Published: August 2003

Gap Junctional Remodeling in Paced Ventricle.
Introduction: Prolonged arrhythmic or paced ventricular activation causes persistent changes in myocardial conduction and repolarization that may result from altered electrotonic current flow, for which gap junctional coupling is the principal determinant. Remodeling of gap junctions and their constituent connexins modifies conduction and has been causally implicated in reentrant arrhythmogenesis. We hypothesized conversely that altering the pattern of ventricular activation causes gap junctional remodeling.

Methods and Results: Seven dogs were paced from the left ventricular (LV) epicardium (VVO, ~120 beats/min) for 21 days before excision of transmural LV samples that were divided into endomyocardial, mid‐myocardial, and epimyocardial layers. Another five paced dogs had recording electrodes attached to multiple LV sites. All 12 dogs developed characteristic pacing‐induced persistent T wave changes of cardiac memory. After 21 days of pacing, the ventricularly paced QRS duration prolonged by a mean of 4 msec over baseline (P < 0.05), a change that was associated with significant slowing of intraventricular conduction to local sites. These changes in QRS duration and repolarization were associated with a reduction in epimyocardial connexin43 expression on quantitative Western blotting of LV myocardium from close to, but not distant from, the pacing site (61.7 ± 18.4 vs 100.9 ± 34.0; P < 0.02) and a marked disruption in immunolabeled connexin43 distribution in epimyocardium only.

Conclusion: Spatially distinct transmural and regional gap junctional remodeling is a consequence of abnormal ventricular activation and is associated with consistent changes in activation that may alter patterns of repolarization and facilitate reentrant arrhythmogenesis.
Reentry Site During Fibrillation Induction in Relation to Defibrillation Efficacy for Different Shock Waveforms
Authors: IDEKER RAYMOND E. , ALFERNESS CLIF , MELNICK SHARON , SREENAN KATE M. , JOHNSON ERIC , SMITH WILLIAM M.
Published: August 2003

Reentry Site and Defibrillation Waveform Efficacy.
Introduction: Unsuccessful defibrillation shocks may reinitiate fibrillation by causing postshock reentry.

Methods and Results: To better understand why some waveforms are more efficacious for defibrillation, reentry was induced in six dogs with 1‐, 2‐, 4‐, 8‐, and 16‐msec monophasic and 1/1‐ (both phases 1 msec) 2/2‐, 4/4‐, and 8/8‐msec biphasic shocks. Reentry was initiated by 141 ± 15 V shocks delivered from a defibrillator with a 150‐ μ F capacitance during the vulnerable period of paced rhythm (183 ± 12 msec after the last pacing stimulus). The shock potential gradient field was orthogonal to the dispersion of refractoriness. Activation was mapped with 121 electrodes covering 4 × 4 cm of the right ventricular epicardium, and potential gradient and degree of recovery of excitability were estimated at the sites of reentry. Defibrillation thresholds (DFTs) were estimated by an up‐down protocol for the same nine waveforms in eight dogs internally and in nine other dogs externally. DFT voltages for the different waveforms were positively correlated with the magnitude of shock potential gradient and negatively correlated with the recovery interval at the site at which reentry was induced by the waveform during paced rhythm for both internal (DFT = 1719 + 64.5 ∇ V − 11.1RI; R2= 0.93) and external defibrillation (DFT = 3445 + 150 ∇ V − 22RI; R2= 0.93).

Conclusion: The defibrillation waveforms with the lowest DFTs were those that induced reentry at sites of low shock potential gradient, indicating efficacious stimulation of myocardium. Additionally, the site of reentry induced by waveforms with the lowest DFTs was in myocardium that was more highly recovered just before the shock, perhaps because this high degree of recovery seldom occurs during defibrillation due to the rapid activation rate during fibrillation.
Focal Atrial Fibrillation: Experimental Evidence for a Pathophysiologic Role of the Autonomic Nervous System
Authors: SCHAUERTE PATRICK , SCHERLAG BENJAMIN J. , PATTERSON EUGENE , SCHERLAG MICHAEL A. , MATSUDARIA KAGARI , NAKAGAWA HIROSHI , LAZZARA RALPH , JACKMAN WARREN M.
Published: August 2003

Focal AF and Autonomic Nerves.
Introduction: Focal paroxysmal atrial fibrillation (AF) was shown recently to originate in the pulmonary veins (PVs) and superior vena cava (SVC). In the present study, we describe an animal model in which local high‐frequency electrical stimulation produces focal atrial activation and AF/AT (atrial tachycardia) with electrogram characteristics consistent with clinical reports.

Methods and Results: In 21 mongrel dogs, local high‐frequency electrical stimulation was performed by delivering trains of electrical stimuli (200 Hz, impulse duration 0.1 msec) to the PVs/SVC during atrial refractoriness. Atrial premature depolarizations (APDs), AT, and AF occurred with increasing highfrequency electrical stimulation voltage. APD/AT/AF originated adjacent to the site of high‐frequency electrical stimulation and were inducible in 12 of 12 dogs in the SVC and in 8 of 9 dogs in the left superior PV (left inferior PV: 7/8, right superior PV: 6/8; right inferior PV: 4/8). In the PVs, APDs occurred at 13 ± 8 V and AT/AF at 15 ± 9 V (P < 0.01; n = 25). In the SVC, APDs were elicited at 19 ± 6 V and AT/AF at 26 ± 6 V (P < 0.01; n = 12). High‐frequency electrical stimulation led to local refractory period shortening in the PVs. The response to high‐frequency electrical stimulation was blunted or prevented after beta‐receptor blockade and abolished by atropine. In vitro, high‐frequency electrical stimulation induced a heterogeneous response, with shortening of the action potential in some cells (from 89 ± 35 msec to 60 ± 22 msec; P < 0.001; n = 7) but lengthening of the action potential and development of early afterdepolarizations that triggered APD/AT in other cells. Action potential shortening was abolished by atropine.

Conclusion: High‐frequency electrical stimulation evokes rapid ectopic beats from the PV/SVC, which show variable degrees of conduction block to the atria and induce AF, resembling findings in patients with focal idiopathic paroxysmal AF. The occurrence of the arrhythmia in this animal model was likely due to alterations in local autonomic tone by high‐frequency electrical stimulation. Further research is needed to prove absolutely that the observed effects of high‐frequency electrical stimulation were caused by autonomic nerve stimulation.
Atypical Left Atrial Flutter after Intraoperative Radiofrequency Ablation of Chronic Atrial Fibrillation: Successful Ablation Using Three‐Dimensional Electroanatomic Mapping
Authors: DURU FIRAT , HINDRICKS GERD , KOTTKAMP HANS
Published: August 2003

Left Atrial Flutter Ablation. Curative treatment of chronic atrial fibrillation (AF) remains a challenging task for electrophysiologists. Eliminating the initiating triggers by focal radiofrequency ablation in a subset of patients with paroxysmal AF and modifying the maintaining substrate by performing linear lesions within the left atrium in patients with prolonged episodes of AF are among the alternative approaches for management of these patients. Recently, a new intraoperative treatment procedure aimed at eliminating left atrial anatomic “anchor” reentrant circuits by induction of contiguous lesions using radiofrequency energy under direct vision was introduced. However, atypical left atrial flutter may occur during follow‐up after intraoperative ablation of AF. These arrhythmias most likely are due to discontinuities in linear lesions; therefore, they can be successfully mapped and ablated in a subsequent percutaneous catheter ablation procedure. We report and discuss the case of a patient who underwent successful intraoperative ablation of chronic AF, but who developed atypical left atrial flutter postoperatively. Three‐dimensional nonfluoroscopic electroanatomic mapping revealed a gap in the linear lesion line connecting the left upper and right upper pulmonary vein orifices. Ablation at the exit site of the breakthrough was successful.