bluuebunny/crossref_metadata_2025_split huggingface dataset:
Block of HERG Potassium Channels by the Antihistamine Astemizole and its Metabolites Desmethylastemizole and Norastemizole
Authors: ZHOU ZHENGFENG , VORPERIAN VICKEN R. , GONG QIUMING , ZHANG SHETUAN , JANUARY CRAIG T. 
Published: April 2007

Electrophysiologic Effects of Astemizole Metabolites.Introduction: The selective H1‐receptor antagonist astemizole (Hismanal) causes acquired long QT syndrome. Astemizole blocks the rapidly activating delayed rectifier K+current IKrand the human ether‐a go‐go‐related gene (HKRG) K+channels that underlie it. Astemizole also is rapidly metabolized. The principal metabolite is desmethylastemizole, which retains H1‐receptor antagonist properties, has a long elimination time of 9 to 13 days, and its steady‐state serum concentration exceeds that of astemizole by more than 30‐fold. A second metabolite is norastemizole, which appears in serum in low concentrations following astemizole ingestion and has undergone development as a new antihistamine drug. Our objective in the present work was to study the effects of desmethylastemizole, norastemizole, and astemizole on HERG K+channels.Methods and Results: HERG channels were expressed in a mammalian (HEK 293) cell line and studied using the patch clamp technique. Desmethylastemizole and astemizole blocked HERG current with similar concentration dependence (half‐maximal block of 1.0 and 0.9 nM, respectively) and block was use dependent. Norastemizole also blocked HERG current; however, block was incomplete and required higher drug concentrations (half‐maximal block of 27.7 nM).Conclusions: Desmethylastemizole and astemizole cause equipotent block of HERG channels, and these are among the most potent HERG channel antagonists yet studied. Because desmethylastemizole becomes the dominant compound in serum, these findings support the postulate that it becomes the principal cause of long QT syndrome observed in patients following astemizole ingestion. Norastemizole block of HERG channels is weaker; thus, the risk of producing ventricular arrhythmias may be lower. These findings underscore the potential roles of some H1‐receptor antagonist metabolites as K+channel antagonists.
Sudden Death in Recipients of Transvenous Implantable Cardioverter Defibrillator Systems:
Authors: PIRES LUIS A. , HULL MICHAEL L. , NINO CHARLES L. , MAY LYNETTE M. , GANJI JAGADEESH R. 
Published: April 2007

Sudden Death in ICD Recipients. Introduction: Transvenous implantable cardioverter defibrillator (ICD) systems are very effective in preventing sudden death; however, little is known about terminal events and potential causes and mechanisms of sudden death in recipients of these devices. Methods and Results: We analyzed 74 cases of sudden death among patients enrolled in several clinical investigations of transvenous ICD systems. Eighty‐one percent were men (mean age 68 ± 10 years), 86% had coronary artery disease, mean left ventricular ejection fraction was 0.27 ± 0.11, and two thirds presented with sustained ventricular tachycardia. The final event was witnessed in 65 patients (81%). Based on reported ICD shocks, documented rhythm, and/or postmortem device data, sudden death was deemed tachyarrhythmic in 49 cases (66%), non‐tachyarrhythmic in 12 (16%), and indeterminate in the remaining 13 (18%). Multivariate analysis of several clinical and nonclinical factors found advanced age (>65 years, P = 0.03, odds ratio [OR] 1.75, 95% confidence interval [CI] 1.05 to 2.92), reduced left ventricular ejection fraction (< 0.35, P < 0.01, OR 3.51, CI 1.66 to 7.40), and having antibradycardia pacing ICDs (P = 0.02, OR 5.26, CI 1.37 to 20.0) to be independent predictors of sudden death. One or more predisposing factors and/or potential causes of sudden death were identified in 21 patients (28%). Conclusion: In this select group of transvenous ICD recipients, (1) sudden death was associated with ventricular tachycardia/ventricular fibrillation in at least two thirds of cases, (2) nearly one third of patients had one or more factors, some device related, that could have been associated with sudden death, and (3) death ensued despite appropriate ICD therapies and, in many cases, external resuscitation, suggesting acute adverse events as common terminal factors.
Effect of the Implantable Atrial Defibrillator on the Natural History of Atrial Fibrillation
Authors: TSE HUNG‐FAT , LAU CHU‐PAK , YU CHEUK‐MAN , LEE KATHY L.F. , MICHAUD GREGORY F. , KNIGHT BRADLEY P. , MORADY FRED , STRICKBERGER S. ADAM 
Published: April 2007

Implantable Atrial Defibrillator. Introduction: The purpose of our study was to evaluate the effect of repeated cardioversion with an implantable atrial defibrillator on the clinical outcome of patients with atrial fibrillation. Methods and Results: The effects of the implantable atrial defibrillator on the total duration of atrial fibrillation, number of atrial fibrillation recurrences, and left atrial size were evaluated prospectively in 16 patients with atrial fibrillation (13 men and 3 women; mean age 58 ± 11 years). Seven patients bad no cardiovascular disease, 5 patients had hypertension. 3 patients had coronary heart disease, and 1 patient bad congenital heart disease. Eight patients had paroxysmal atrial fibrillation for a mean duration of 80 ± 61 months, and eight patients had persistent atrial fibrillation for a mean duration of 68 ± 119 months. Except for one patient who received digoxin throughout the study, alt patients received the same Class I or III antiarrhythmic agent throughout the study. The implantable atrial defibrillator successfully converted 50 (93%) of 54 spontaneous episodes of atrial fibrillation in 12 patients. During the initial 3 months of clinical follow‐up, the atrial defibrillator documented 261 ± 270 hours of atrial fibrillation compared with 126 ± 172 hours (P = 0.01) during the subsequent 3 months. The left atrial size decreased from 4.4 ± 0.7 cm at the time of atrial defibrillator implantation to 4.1 ± 0.6 cm (P = 0.02) 6 months later. The number of atrial fibrillation recurrences did not change. These findings were observed in the absence of changes in drug therapy. No complications were observed. Conclusion: Restoration and maintenance of sinus rhythm in patients with atrial fibrillation by repeated cardioversion with an implantable atrial defibrillator was associated with a reduction in the total arrhythmia duration and a reduction in left atrial size. These results suggest that maintenance of sinus rhythm with the atrial defibrillator may reverse the remodeling process associated with atrial fibrillation.
Differing Rate Dependence and Temporal Distribution of Repolarization Alternans in Patients with and without Ventricular Tachycardia
Authors: NARAYAN SANJIV M. , SMITH JOSEPH M. 
Published: April 2007

Temporal Dynamics of Repolarization Alternans. Introduction: Repolarization atlternans(RPA) may reflect repolarization heterogeneities underlying VT, yet its temporal dynamics are poorly understood. We hypothesized (hat RPA occurring late, rather than early, with in repolarization reflects a temporal variation in recovery that may predispose to wave front fractionation and the initiation of reentrant VT, and that this temporal distribution may vary with heart rate. Methods and Results: ECG leads I, aVF, and V1 were recorded in 40 patients during; electrophysiologic study. RPA across the JT interval was computed. spectrally for 64‐heatsequences at paced cycle lengths (CLs) of 600, 500, and 400 msec, and expressed as the T wave alternans ratio (TWAR) on the vector ECG lead. Significant RPA (TWAR ≥ 3) was reconstructed into the time domain, and its center of area used to represent its temporal distribution. Twenty‐two patients were inducible into VT and 18 were not. RPA was of larger magnitude in Inducible than noninducible patients (TWAR = 11.1 vs 4.42, P = 0.035; 38.3 vs 5.74, P = 0.004;and 88.8 vs 4.2S. P = 0.001 in each, respectively), and was distributed later (P < 0.02; CL 600msec). Applying TWAR ≥ 3 to the distal half of the JT segment produced greater specificity for inducible VT (88.9%, 66.7%, and 69.2% at each CL, respectively) than did RPA of the entire JT segment (77.8%. 53.3%, and 69.2%) Conclusion: RPA is more specific for inducible VT when distributed late rather than else wherein repolarization, and this temporal distribution is heart rate sensitive. Further study is required to interpret these findings in the context of temporal dispersion of refractoriness.
Automatic and Efficient R Wave Discrimination in the Right Atrium Using a Two‐State Hidden Markov Model
Authors: SUN WEIMIN , COMBS WILLIAM , PANKEN ERIC , FOTUHI PARWIS , STANGL KARL , BAUMANN GERT , THERES HEINZ 
Published: April 2007

Far‐Field R Wave Detection Using an HMM. Introduction: Discrimination of far‐field R waves from atrial events in atrial electrograms (EGMs) is problematic in present implantable pacing systems. Adjustments of atrial refractory periods and sensitivity settings are the only options, and they will not provide optimal performance in many patients. The reliable detection or rejection of R waves in atrial EGMs would avoid problems of atrial undersensing or oversensing, thus benefiting DOD patients by providing more reliable and specific atrial arrhythmia detection. In addition, detection of far‐field R waves could allow a measurement of AV conduction time in AAI and aid in discrimination of supraventricular tachyarrhythmia from ventricular tachyarrhythmia. Methods and Results: Both atrial and ventricular unipolar EGMs were collected from 25 patients undergoing pacemaker implant or replacement. An average of 141 seconds of intrinsic or VVI paced EGMs was recorded and post analyzed. A new two‐state hidden Markov model (HMM) was developed specifically for far‐field R wave and P wave discrimination in the atrium. The recorded patients' EGMs were analyzed using this model, and the sensitivity and positive predictivity of far‐field R wave detection were evaluated. The collected atrial EGMs were visually examined and marked as the control for verification of the detection analysis. Far‐field R wave detection using this model had an overall sensitivity of 94%± 9.4% and a positive predictivity of 98.3%± 4.4%; and the far‐field R wave rejection using the same model had a sensitivity and a positive predictivity of 98.8%± 3.8% and 99.1%± 1.7%, respectively. Conclusion: Far‐field R wave detection in the right atrium by the two‐state HMM is reliable and accurate, and can significantly improve atrial arrhythmia management for patients.
Intracardiac Echocardiography to Guide Transseptal Left Heart Catheterization for Radiofrequency Catheter Ablation
Authors: DAOUD EMILE G. , KALBFLETSCH STEVEN J. , HUMMEL JOHN D. 
Published: April 2007

Transseptal Catheterization. Introduction: The purpose of this study was to asess the feasibility and safety of intracardiac echocardiography to guide transseptal puncture for radiofrequency catheter ablation. Methods and Results: Transcatheter intracardiac echocardiography (9 MHz) was utilized to guide transseptal puncture in 53 patients undergoing radiofrequency catheter ablation. The anatomy and relationship of intra‐ and extracardiac structures were visualized with the ultrasound transducer positioned at the fossa ovalis. The tip of the transseptal dilator and tenting of the fossa ovalis and the left atrial wall were simultaneously visualized in a single ultrasound image in all patients. With maximum tenting of the fossa ovalis, the mean distance from the fossa to the left atrial wall was 11.9 ± 5.8 mm (range: 1.8 to 25.6 mm). In four patients (8%), the tented fossa ovalis abutted the left atrial wall and the transseptal dilator was redirected with ultrasound guidance. Puncture of the interatrial septum was achieved through the fossa ovalis in each patient and required a single attempt in 51 patients (96%). The mean number of punctures per patient was 1.1 ± 0.4. The mean time to perform transseptal catheterization was 18.2 ± 6.8 minutes. There were no complications. Conclusion: Intracardiac echocardiography delineated the anatomy of intra‐ and extracardiac structures not identified with fluoroscopy and simplified correct positioning of the transseptal dilator, puncture of the fossa ovalis, and cannulation of the left atrium in a timely and uncomplicated fashion.
Relationship Between Shock Energy and Postdefibrillation Ventricular Arrhythmias in Patients with Implantable Defibrillators
Authors: ZIVIN ADAM , SOUZA JOSEPH , PELOSI FRANK , FLEMMING MATTHEW , KNIGHT BRADLEY P. , GOYAL RAJIVA , MORADY FRED , STRICKBERGER S. ADAM 
Published: April 2007

Postdefibrillation Ventricular Arrhythmias. Background: The relationship between postdefibrillation ventricular arrhythmias and shock strength is poorly understood in patients with implantable defibrillators. The purpose of this study was to characterize the relationship between postdefibrillation ventricular arrhythmias and shock strength. Methods and Results: Forty‐three patients with an implanted defibrillator underwent six separate inductions of ventricular fibrillation (VF) after a step‐down defibrillation energy requirement (7.3 ± 4.6 J) was determined. For each of the first three inductions of VF, the first two shocks were low energy and equal to approximately 75 % of the defibrillation energy requirement (5.4 ± 3.3 J), or to the defibrillation energy requirement plus 10 J (17.5 ± 4.3 J). After the first two shocks, subsequent shocks were programmed to the maximum available energy (29.0 ± 2.5 J). The alternate technique was used for the subsequent three inductions of VF. Post defibrillation ventricular arrhythmias were noted. Post defibrillation ventricular arrhythmias with a cycle length ≤ 300 msec were more frequent after a low‐energy shock (19%), than after a high‐energy shock (1.5 %; P = 0.005). Postdefibrillation ventricular arrhythmias with a cycle length > 300 msec were more frequent after a high‐energy shock (32%), than after a low‐energy shock (7.1%; P = 0.002). A relationship between the cycle length of the post defibrillation ventricular arrhythmias and the absolute defibrillation energy was observed (P < 0.001; r = 0.6), and ventricular arrhythmias with a cycle length > 300 msec were uncommon after shocks ≤ 10 J (P = 0.001). The characteristics of ventricular arrhythmias after maximum‐energy shocks were similar to those that occurred after high‐energy shocks. Conclusions: Post defibrillation ventricular arrhythmias with a cycle length ≤ 300 msec are more common after shocks of strength associated with a low probability of successful defibrillation. Postdefibrillation ventricular arrhythmias with a cycle length of > 300 msec are more common after high‐ and maximum‐energy shocks, and are directly related to the absolute defibrillation energy.
Locating Ectopic Foci
Authors: HALL KEVIN , GLASS LEON 
Published: April 2007

Locating Ectopic Foci. Introduction: Successful radiofrequency of an ectopic focus requires accurate localization of the region of enhanced automaticity. Present localization techniques require detailed electrical mapping that is time‐consuming and involves much trial and error. Here, we propose two new localization techniques which were used to locate a pacemaker in a computer simulation. Methods and Results: We suggest that an ectopic focus can he located by measuring the activation sequence of three or more intracardiac electrodes subsequent to an ectopic depolarization. Furthermore, the resetting response of an ectopic pacemaker can be used to estimate the distance from the stimulation electrode to the ectopic focus. We derive simple geometric localization strategies based on these ideas and examine the sensitivity of the strategies with respect to measurement uncertainties and electrode arrangements. Our localization strategies were tested using a numerical simulation of a pacemaker in a sheet of excitable media described by modified FitzHugh‐Nagumo equations. The strategy based on electrode activation sequences located the pacemaker region in a homogeneous isotropic sheet after an average of 2.2 ± 0.8 iterates in 10 out of 10 trials starting from random initial catheter positions. In the case of an inhomogeneous anisotropic sheet, the pacemaker was located after an average of 4 ± 3 iterates in 9 out of 10 trials. The localization strategy based on resetting successfully found the pacemaker in a homogeneous isotropic sheet after an average of 1.2 ± 0.4 iterates in 5 out of 5 trials and localized the pacemaker in an inhomogeneous anisotropic sheet after an average of 1.4 ± 0.5 iterates in 5 out of 5 trials. Conclusions: Simple geometric strategies can be used to locate an ectopic focus. Although our basic localization strategies are sensitive to the electrode arrangement and measurement uncertainties, we show that iteration of our techniques quickly locates the pacemaker.
Differential Effects of Adenosine on Focal and Macroreentrant Atrial Tachycardia
Authors: MARKOWITZ STEVEN M. , STEIN KENNETH M. , MITTAL SUNEET , SLOTWTNER DAVID J. , LERMAN BRUCE B. 
Published: April 2007

Focal and Macroreentrant Atrial Tachycardia. Introduction: The effects of adenosine on atrial tachycardia (AT) remain controversial, and the mechanistic implications of adenosine termination have not been fully established. The purpose of this study was to elucidate the differential effects of adenosine on focal and macroreentrant AT and describe the characteristics of adenosine‐sensitive AT. Methods and Results: Thirty patients received adenosine during AT. Tachycardia origins were identified as local or macroreentrant during invasive electrophysiologic studies. Responses to adenosine were analyzed and characterized as tachycardia termination, transient suppression, or no effect. Electrophysiologic studies demonstrated a focal origin of tachycardia in 17 patients. Adenosine terminated focal tachycardias in 14 patients (dose 7.3 ± 4.0 mg) and transiently suppressed the arrhythmias in three others (dose 10.0 ± 6.9 mg). A macroreentrant mechanism was demonstrated in 13 patients: adenosine terminated only one of these tachycardias and had no effect on the remaining 12 patients (dose 10.2 ± 2.9 mg). Four classes of adenosine‐sensitive AT were identified. Class I consisted of nine patients with tachycardia arising from the crista terminalis; these tachycardias also terminated with verapamil (4/4). Class II consisted of four patients with repetitive monomorphic AT arising from diverse sites in the right atrium; these either slowed or terminated in response to verapamil (2/2). Class III consisted of the three patients with transient suppression and demonstrated electropharmacologic characteristics consistent with an automatic mechanism, including insensitivity to verapamil (2/2). In the one patient with macroreentrant AT that was comprised of decremental atrial tissue, adenosine terminated tachycardia in a zone of decremental slow conduction (Class IV); this tachycardia slowed with verapamil. Conclusions: Adenosine‐sensitive AT is usually focal in origin and arises cither from the region of the crista terminalis (inclusive of the sinus node) or from diverse atrial sites with an incessant nonsustained repetitive pattern. Although most forms of macroreentrant AT are insensitive to adenosine, rarely macroreentrant AT with zones of decremental slow conduction can demonstrate adenosine sensitivity.
The Activation of Platelet Function, Coagulation, and Fibrinolysis during Radiofrequency Catheter Ablation in Heparinized Patients
Authors: ANFINSEN OLE‐GUNNAR , GJESDAL KNUT , BROSSTAD FRANK , ORNING OTTO M. , AASS HALFDAN , KONGSGAARD ERIK , AMLIE JAN P. 
Published: April 2007

Hemostatic Activation during RF Ablation. Introduction: Catheter ablation may be complicated by clinical thromboembolism in about 1% of patients. Methods and Results: We studied the activation of coagulation (prothrombin fragment 1+2 [PFl+2]). platelets (β‐thromboglobulin [β‐TG])) and fibrinolysis (plasmin‐antiplasmin complexes [PAP) and D‐dimer) during radiofrequency (RF) ablation in 13 patients. They received heparin 100 U/kg intravenously alter the initial electrophysiologic study, prior to the delivery of RF current; thereafter 1,000 U/hour throughout the procedure. PF1+2 increased fourfold (P < 0.001) during the diagnostic study, but gradually declined to upper reference value during heparin administration. There was a strong correlation between procedure duration prior to heparin bolus (range 39 to 173 min); and (a) the maximal rise of PFl+2 (r = 0.83, P < 0.001) and (b) the increase of PFI+2 from baseline to end of the procedure (r = 0.74, P = 0.004). There was no correlation between postheparin changes of PFl+2 and (a) postheparin procedure duration (range 40 to 317 min), (b) number of RF pulses (range 1 to 16). or (c) RF current duration (range 46 to 687 sec). Plasma β‐TG concentration showed similar trends. Fibrinolytic activity increased moderately from baseline until heparin administration; then remained around the upper reference values. PAP at the end of procedure and D‐dimer at the time of heparin administration both correlated with preheparin procedure duration (r = 0.70, P = 0.007 and r = 0.69, P = 0.01. respectively). All parameters were normal the next morning. Conclusion: Procedure duration prior to heparin administration, and not the delivery of RF current per se, determines activation of hemostasis and fibrinolysis during RF ablation.
Distinctive RR Dynamics Preceding Two Modes of Onset of Spontaneous Sustained Ventricular Tachycardia
Authors: ANDERSON KELLEY P. , SHUSTERMAN VLADIMIR , AYSIN BENHUR , WEISS RAUL , BRODE SUSAN , GOTTIPATY VENKATESHWAR ,   for the ESVEM Investigators
Published: April 2007

RR Dynamics Before VT. Introduction: We hypothesized that autonomic activity preceding spontaneous sustained monomorphic ventricular tachycardia (VTsm) as assessed by heart rate (HR) and RR interval variability (RRV) differs between type 1 VTsm which is initiated by morphologically distinct, early cycle, possibly triggering premature ventricular complexes (PVCs) and type 2 VTsm in which the initial complex has a QRS waveform identical to subsequent complexes. Methods and Results: Baseline Holter tapes (1,646) from a clinical trial were scanned for VTsm. QRS complexes of VTsm, were compared by two‐lead cross‐correlation to distinguish type 1 and type 2 VTsm, Frequency domain RRV index were estimated over 5 minutes, 15 minutes, and 24 hours. Type 1 and type 2 VTsm, were present in 15 (group 1) and 33 (group 2) of 48 patients, respectively. HR did not change in group 1 (88.4 ± 15.2 to 89.7 ± 13.0 beats/min, P = 0.89), but increased before the onset of VTsm in group 2 (74.3 ± 16.3 to 81.2 ± 18.0 beats/min, P < 0.001). RRV index were severely depressed in both groups. No RRV index changed significantly before the onset of type 1 VTsm, whereas significant changes occurred before type 2 VTsm from 24‐hour average to 30 minutes before VTsm in very low (very low‐frequency power [VLFP]: 6.62 ± 1.53 to 6.20 ± 2.07 In msec2, P = 0.036), low (low‐frequency power [LFP]: 5.61 ± 1.43 to 5.28 ± 1.59 in msec2, P = 0.004), normalized low (normalized low‐frequency power [LFPn]: ‐0.48 ± 0.58 to ‐0.55 ± 0.64 normalized units [nu], P = 0.05) and the ratio of LFP to high‐frequency power (HFP) (LPP/HFP: 4.20 ± 3.47 to 3.45 ± 2.53, P = 0.017). Declines in RRV index between 2 hours to the 30‐minute period before VTsm, occurred in group 2 but not group 1 in LFP (5.85 ± 1.42 to 5.28 ± 1.59 In msec, P = 0.043) and HFP (4.94 ± 5.14 to 3.46 ± 2.52 In msec2 P = 0.008), with a downward trend in LFP/HFP (4.94 ± 5.14 to 3.45 ± 2.53, P = 0.127) and LFPn (‐0.38 ± 0.36 to ‐0.55 ± 0.64, P = 0.15), while HFPn tended to rise (‐1.47 ± 0.65 to ‐1.27 ± 0.64, P = 0.15). Conclusions: HR and RRV did not change before type 1 VTsm, suggesting that short‐term changes in autonomic activity were not essential to initiation of apparent PVC‐triggered VTsm. In contrast, RR interval dynamics before type 2 VTsm suggested that short‐term changes in neurohormonal activity contributed to arrhythmia initiation. Heterogeneities in arrhythmia onset may reflect distinct triggers and substrate properties that could provide a basis for effective therapeutic targets.