bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Donor Splice Site Mutation in the KVLQT1 Gene is Associated with Long QT Syndrome
Authors: KANTERS JØRGEN K. , LARSEN LARS ALLAN , ORHOLM MARIANNE , AGNER ERIK , ANDERSEN PAAL SKYTT , VUUST JENS , CHRISTIANSEN MICHAEL 
Published: April 2007

KVLQT1 Gene Mutation and LQTS. Introduction: Inherited long QT syndrome (LQTS) recently has been associated with mutations in genes coding for potassium (KVLQTI, KCNEI, and HERG) or sodium (SCN5A) ion channels involved in regulating either sodium inward or potassium outward currents of heart cells, resulting in prolongation of the repolarization period. We describe a new mutation, a‐1 donor splice site mutation in a kindred with two affected members (QTc = 0.61 and 0.54 sec). Methods and Results: Single stranded conformation polymorphism (SSCP) analyses were performed on DNA fragments amplified by polymerase chain reaction from DNA extracted from whole blood. Aberrant conformers were analyzed by DNA sequencing. SSCP analysis of the KVLQTI gene revealed an aberrant conformer in the affected family members. DNA sequencing confirmed the presence of a G→A change in the last nucleotide of codon 344. This mutation does not cause an amino acid change, but a change of the splice site characteristics at the 3’end of exon 6. The mutation may affect, through deficient splicing, the putative sixth transmembrane segment of the K+ channel, and this type of mutation has not previously been described in KVLQTI. Conclusion: The clinical course of LQTS in the affected family members, in whom no deaths occurred despite 20 to 30 syncopes, can he explained by the ability of the cellular machinery to perform partial correct splicing in the mutant allele. This type of mutation may be misinterpreted as a normal variant, since it is a point mutation causing neither an amino acid change nor the introduction of a stop codon.
Origin of Heat‐Induced Accelerated Junctional Rhythm
Authors: THIBAULT BERNARD , de BAKKER JACQUES M.T. , HOCINI MÉLÈZE , LOH PETER , WITTKAMPF FRED H.M. , JANSE MICHIEL J. 
Published: April 2007

Accelerated Junctional Rhythm. Introduction: The application of high‐frequency current to the AV junctional area results in a temperature rise in the myocardium and may cause accelerated junctional rhythm (AJR). The aim of the study was to characterize heat‐induced AJR in an in vitro animal model. Methods and Results: Studies were performed in isolated perfused pig and rabbit hearts. Using a small heating probe, we could induce AJR from a discrete area located in the middle of the triangle of Koch, which was smaller than the area from which RF energy application could elicit AJR. Histology showed that the heat‐sensitive area was located over, or close to, the compact AV node. It did not correspond with the areas where double potentials were found or with the site(s) of earliest atrial activation during VA conduction. Microelectrode recordings revealed that AJR arose in nodal‐type cells. Heat increased the slope of the phase 4 depolarization and shortened the action potential duration. Two types of AJR were observed: the first one was regular and the second one showed irregularity in the intervals. Interaction of multiple foci and the presence of conduction block between the foci and the His bundle caused the irregularity of the His‐His intervals during the second type of AJR. Conclusion: AJR observed during heat and RF application in the AV nodal area results from the effect of heat on AV nodal cells with underlying pacemaker activity. The heat‐sensitive area is located over, or very close to, the compact AV node.
Detection of Ventricular Fibrillation by Transvenous Defibrillating Leads:
Authors: GOLDBERGER JEFFREY J. , HORVATH GEORGE , DONOVAN DORIS , JOHNSON DAVID , CHALLAPALLI RAM , KADISH ALAN H. 
Published: April 2007

Integrated Versus Dedicated Bipolar Sensing of VF. Introduction: Dedicated bipolar sensing has been suggested to be safer than integrated bipolar sensing due to an increased incidence of failure to redetect ventricular fibrillation after an unsuccessful shock with leads that use integrated bipolar sensing. We compared sensing charactersitics during ventricular fibrillation of simultaneously recorded dedicated and integrated bipolar electrograms. Methods and Results: Thirty patients undergoing transvenous defibrillator implantation with a Transvene lead were studied. Simultaneous recordings were made from the dedicated bipole and the integrated bipole from the distal tip to the coil (interelectrode distance 18.3 mm). The mean detection time and number of undetected beats for the initial episode of ventricular fibrillation were 2804 ± 569 msec and 0.9 ± 0.8 using the dedicated recordings and 2938 ± 546 msec and 1.4 ± 1.1 (P = 0.026) using the integrated recordings. The mean redetection times and number of undetected beats following a failed first shock (n = 13) were 2468 ± 225 msec and 0.8 ± 1.1 for the dedicated recordings and 3042 ± 498 msec (P < 0.0003) and 4.2 ± 4.2 (P < 0.005) for the integrated recordings. Frequency analysis of the ventricular fibrillation electrograms demonstrated that the signal energy in the dedicated electrograms was significantly greater than the energy in the integrated electrograms (P < 0.0001). There was a significant negative relationship between detection times and the ventricular fibrillation signal energy. There was no independent effect of recording type (dedicated versus integrated). Conclusion: There are only minor differences in detection/redetection of ventricular fibrillation between dedicated and integrated (with tip to coil spacing of 18.3 mm) recording configurations. Detection times during ventricular fibrillation are related to the signal variance or energy recorded. Differences in the sensing performance of the two recording configurations can be explained by the differences in signal energy between the dedicated and integrated recordings that occur during ventricular fibrillation.
Effect of Heart Rate on T Wave Alternans
Authors: KAVESH NEAL G. , SHOROFSKY STEPHEN R. , SARANG SAMANTHA E. , GOLD MICHAEL R. 
Published: April 2007

Heart Rate and T Wave Alternans. Introduction: T wave alternans (TWA) is a promising technique for detecting arrhythmia vulnerability. Previous studies in animals demonstrated that the magnitude of TWA is dependent on heart rate. However, the effects of heart rate on TWA in humans and the clinical relevance of this effect remain controversial. Methods and Results: This was a prospective evaluation of pacing rate and monitoring lead configuration on TWA in subjects undergoing electrophysiologic study. Measurements of TWA were performed on 45 patients in the absence of antiarrhythmic drugs. Recordings were made in normal sinus rhythm and during atrial pacing at 100 and 120 beats/min. Sustained monomorphic ventricular tachycardia (VT) was induced in 29 patients with programmed stimulation. TWA in the vector magnitude lead increased with heart rate, independent of VT inducibility (0.4 ± 0.7 μ V, 1.6 ± 1.9 μ V, and 2.4 ± 2.1 μ V in sinus rhythm and at 100 and at 120 beats/min, respectively; P < 0.001). In addition, the diagnostic performance of TWA for inducible VT was dependent on heart rate (sensitivity 4%, 42%, and 65%, and specificity 100%, 93%, and 63% at 77, 100, and 120 beats/min, respectively). By analyzing orthogonal leads rather than the vector magnitude lead, the sensitivity is increased from 42% to 59% at 100 beats/min, but the specificity is reduced from 93% to 72%. Conclusion: These results indicate that TWA in humans is strongly dependent on heart rate with regard to both magnitude and diagnostic performance. The optimal heart rate for the measurement of TWA is between 100 and 120 beats/min and multiple leads should be monitored.
Radiofrequency Modification of the Atrioventricular Node in Patients with Chronic Atrial Fibrillation:
Authors: STABILE GIUSEPPE , TURCO PIETRO , DE SIMONE ANTONIO , COLTORTI FERNANDO , DE MATTEIS CARMINE 
Published: April 2007

RF Modification of AVN in AF. Introduction: We compared, in a prospective and randomized fashion with a cross‐over design, the anterior and posterior approaches to radiofrequency (RF) modification of the AV node in patients with chronic atrial fibrillation. Methods and Results: Thirty‐three patients were randomized to receive first an anterior (group I) or posterior (group II) approach for RF modification of AV nodal conduction. Patients who did not fill the endpoint ventricular rate (< 90 beats/min) were crossed over to the alternative approach. After the anterior approach in group I patients, mean ventricular rate was significantly lower than in group II patients after the posterior approach (79.6 ± 18.8 beats/min vs 110.8 ± 16.2 beats/min, P < 0.001). In group I, 14 (82%) of 17 patients fulfilled the endpoint, 1 (6%) had complete AV block, and 2 (12%) were crossed over to the posterior approach fulfilling the endpoint. In group II, 4 (25%) of 16 patients fulfilled the endpoint. No transient or permanent high‐degree AV block was observed. Among the 12 patients who were crossed over to the anterior approach, 8 fulfilled the endpoint, whereas 4 had permanent high‐degree AV block. RF ablation carried out only in the anterior region was safer than a stepwise approach (6% vs 33% incidence of AV block), even though the difference did not reach statistical significance (P = 0.09). Conclusion: Posterior AV nodal modification is less effective but safer than anterior AV nodal modification. However, to reduce the incidence of AV block, the anterior approach is preferable to a stepwise approach from the posterior to the anterior zone.
Potentiating Effect of Acetylcholine on Stimulation by Isoproterenol of L‐Type Ca2+ Current and Arrhythmogenic Triggered Activity in Guinea Pig Ventricular Myocytes
Authors: SONG YEJIA , SHRYOCK JOHN C. , BELARDINELLI LUIZ 
Published: April 2007

ACh Facilitation of Triggered Activity. Introduction: The objective of this study was to determine whether the effect of isoproterenol (Iso) to increase L‐type Ca2+ current [Ica(L)] and action potential duration (APD) was potentiated in ventricular myocytes following termination of an exposure of these cells to acetylcholine (ACh), and whether this potentiating effect of Ach could he arrhythmogenic. Methods and Results: Transmembrane currents and potentials of guinea pig Isolated ventricular myocytes were measured using the whole cell, patch clamp technique. Stimulation of Ica(L) and prolongation of APD caused by Iso (10 nmol/L) were attenuated in the presence of Ach (10 μ mol/L), but were transiently enhanced by 111%± 20% and 214%± 44%, respectively, following termination of a 2‐ to 4‐minute exposure of myocytes to ACh. No changes were observed in the absence of Iso. Both the amplitude and incidence of isoinduced transient inward current, afterdepolarizations, and sustained triggered activity were greater immediately after termination of exposure to ACh than before application of ACh. Conclusion: Stimulation by Iso of Ica(L) is transiently enhanced in guinea pig ventricular myocytes following termination of exposure of these cells to ACh. The rebound increase of Iso‐stimulated Ica(L) is associated with an increase of APD and induction of arrhythmogenic triggered activity.
Postshock Potential Gradients and Dispersion of Repolarization in Cells Stimulated with Monophasic and Biphasic Waveforms
Authors: SOBIE ERIC A. , TUNG LESLIE 
Published: April 2007

Effects of Monophasic and Biphasic Stimuli. Introduction: Even though the clinical advantage of biphasic defibrillation waveforms is well documented, the mechanisms that underlie this greater efficacy remain incompletely understood. It is established, though, that the response of relatively refractory cells to the shock is important in determining defibrillation success or failure. We used two computer models of an isolated ventricular cell to test the hypothesis that biphasic stimuli cause a more uniform response than the equivalent monophasic shocks, decreasing the likelihood that fibrillation will be reinduced. Methods and Results: Models of reciprocally polarized and uniformly polarized cells were used. Rapid pacing and elevated [K]o were simulated, and either 10‐nisec rectangular monophasic or 5‐msec/5‐msec symmetric biphasic stimuli were delivered in the relative refractory period. The effects of stimulus intensity and coupling interval on response duration and postshock transmembrane potential (Vm) were quantified for each waveform. With reciprocal polarization, biphasic stimuli caused a more uniform response than monophasic stimuli, resulting in fewer large gradients of Vm (only for shock strengths ≤ 1.25× threshold vs ≤ 2.125× threshold) and a smaller dispersion of repolarization (1611 msec2 vs 1835 msec2). The reverse was observed with uniform polarization: monophasic pulses caused a more uniform response than did biphasic stimuli. Conclusion: These results show that the response of relatively refractory cardiac cells to biphasic stimuli is less dependent on the coupling interval and stimulus strength than the response to monophasic stimuli under conditions of reciprocal polarization. Because this may lead to fewer and smaller spatial gradients in Vm, these data support the hypothesis that biphasic defibrillation waveforms will be less likely to reinduce fibrillation. Further, published experimental results correlate to a greater degree with conditions of reciprocal polarization than of uniform polarization, providing indirect evidence that interactions between depolarized and hyper polarized regions play a role in determining the effects of defibrillation shocks on cardiac tissue.
Effects of Blocked Atrial Beats on the Atrioventricular Nodal Recovery Property
Authors: WU JING‐MING , YOUNG MING‐LON , LIN MENG‐HSUN , WOLFE GRACE S. 
Published: April 2007

AVN Recovery Property After Blocked Atrial Beats. Introduction: Blocked atrial beats (AB) usually have concealed AV nodal penetration, which can change the nodal conduction time (AH) of a subsequent beat. However, without an output marker it is difficult to assess their effect on the node. In this report we used all possible parameters as nodal resting time after AB and plotted them against the AH of testing beats to study their effects on the node.Methods and Results: Atrial extrastimulation studies were done in 21 patients in whom one blocked atrial heat (A2B) was observed. Nodal recovery curves were obtained for basic pacing (A1), after a conducted premature heat (A2), and after A2B. In six patients there were 2 to 3 consecutively blocked beats (AnB) and recovery curves were constructed after each AnB. Nodal recovery curves were plotted with AH of the testing beat against different nodal resting parameters and fitted to a single exponential equation. We found contradicting phenomena when using different formats. (1) For recovery curves of A2B, there was a rightward shift from that of the basic curve when using H1A3 or A1A3 as the gauge (depression phenomenon). On the contrary, there was a leftward shift of the curves when using A2BA3 (facilitating phenomenon). (2) For recovery curves after multiple blocked beats there was a marked rightward shift of all curves except A(n‐1)BAn ‐curves, which were all leftward shifted.Conclusion: Because these contradicting phenomena were dictated by the presenting formats, the terms “depression” and “facilitation” cannot he considered intrinsic AV nodal properties outside of the strict context of the pacing protocol and the format of data presentation.
Body Surface Potentials During Discharge of the Implantable Cardioverter Defibrillator
Authors: PETERS WERNER , KOWALLIK PETER , REISBERG MANFRED , MEESMANN MALTE 
Published: April 2007

Body Surface Potentials During ICD Discharge. Introduction: Little is known about the hazard for persons in contact with patients experiencing a high‐voltage discharge of their implantable cardioverter defibrillator (ICD). Compared to epicardial systems, this risk may be increased with transvenous electrode systems and particularly in active can configurations.Methods and Results: In 23 patients with a transvenous active can ICD system, body surface potentials VS and current through an external resistance were measured during 35 discharges. VS was detected using skin electrodes positioned over the left subpectorally implanted pulse generator [C], apex of the heart [A], and the right pectoral region [RP]. Mean VS during discharges without an external shunt resistance ranged between 13 and 63.8 V [C to A] and 12.5 to 47.3 V [C to RP] (ICD peak stored/output voltage Vcap= 183 to 606 V, n = 20). Mean current flow [C to A] was 8.2 to 46.8 mA (Vcap= 288 to 633 V. n = 10) and 42 to 120.7 mA (Vcap= 447 to 579 V, n = 5) across a resistance of 1.696 and 797 ω, respectively.Conclusion: During high‐output shocks, a considerable potential difference is present on the hody surface of ICD patients that, according to the literature, may induce a single cardiac response in a bystander. Analogous to spontaneous extrasystoles, there is only a minimal chance of triggering a tachyarrhythmia by this stimulated extra beat. Direct induction of ventricular fibrillation is unlikely, since reported fibrillation threshold values are much higher than the ohserved magnitudes of current and voltage.
Combination of Sotalol and Quinidine in a Canine Model of Torsades de Pointes
Authors: CHÉZALVIEL‐GUILBERT FRÉDÉRIQUE , DEPLANNE VALÉRIE , DAVY JEAN‐MARC , POIRIER JEAN‐MARIE , XIA YONG‐ZHONG , CHEYMOL GEORGES , WEISSENBURGER JACQUES 
Published: April 2007

Sotalol Plus Quinidine and Torsades de Pointes. Introduction: Clinical treatment with a combination of Class IA and III antiarrhythmic drugs is not recommended, as they both favor bradycardia‐dependent proarrhythmic events such as torsades de pointes (TdP). However, this theoretical additive effect on ventricular repolarization has never heen demonstrated and could be questioned as other Class I drugs, such as mexiletine, a Class IB drug, limit the number of sotalol‐induced TdP in dogs with AV block, suggesting the possibility of an antagonistic action of Class I properties against Class III effects.Methods and Results: We compared the electrophysiologic and proarrhythmic effects of sotalol (Class III) alone and combined with quiuidine (Class IA) in a canine model of acquired long QT syndrome. Seven hypokalemic (K*: 3 ± 0.1 mEq/L) dogs with chronic AV block had a demand pacemaker implanted and set at a rate of 25 beats/min. They were submitted to two (sotatol‐alone and sotalol‐plus‐quinidine) experiments 48 bours apart usiug a randomized cross‐over protocol. They were pretreated with quinidine (10 mg/kg + 1.8 mg/kg per hour) or saline infused throughout the experiment, aud given sotalol (4.5 mg/kg + 1.5 mg/kg per hour) for 2 hours, 30 minutes after the beginning of the pretreatment infusion during both experiments. Ventricular and atrial cycle lengths were similarly increased by sotalol after quinidine or saline. The sotalol‐induced prolongation of the QT interval was significantly shorter in quinidine‐pretreated dogs (24 ± 7 msec after quinidine vs 40 ± 8 msec after saline). Fewer dogs developed TdP: significantly during the first hour of infusion (1/7 sotalol‐plus‐quinidine vs 6/7 sotalol‐alone dogs, P < 0.05) but nonsignificantly during the second hour (3/7 vs 6/7).Conclusion: In this model, the sotalol‐plus‐quinidine combination is at least no more arrhythmogenic than either of the drugs given alone.
Effects of Electrophysiologic‐Guided Therapy with Class IA Antiarrhythmic Drugs on the Long‐Term Outcome of Patients with Idiopathic Ventricular Fibrillation with or without the Brugada Syndrome
Authors: BELHASSEN BERNARD , VISKIN SAMI , FISH ROMAN , GLICK AHARON , SETBON ISRAEL , ELDAR MICHAEL 
Published: April 2007

Electrophysiologic Drug Testing in Idiopathic VF. Introduction: Implantation of a implantable cardioverter defibrillator (ICD) is viewed universally as the “gold standard” therapy for patients with idiopathic ventricular fibrillation (VF). We sought to study the long‐term value of electrophysiologic (EP)‐guided therapy with Class IA antiarrhythmic drugs in patients with idiopathic VF with or without the Brugada syndrome. Methods and Results: We performed EP studies in 34 consecutive patients who had idiopathic VF with (n = 5) or without (n = 29) the Brugada syndrome. All patients with inducible sustained polymorphic ventricular tachycardia (SPVT) or VF underwent repeated EP evaluation after oral administration of a Class IA antiarrhythmic drug (mainly quinidine). Patients rendered noninducible received this therapy on a long‐term basis. SPVTA/VF were induced in 27 (79.4%) patients at baseline studies. Class IA drugs effectively prevented induction of SPVTA'F in 26 (96%) patients. Of the 23 patients treated with these medications, no patient died or had a sustained ventricular arrhythmia during a mean follow‐up period of 9.1 ± 5.6 years (7 to 20 years in 15 patients). Two deaths occurred in patients without inducible SPVTA'F at baseline studies who had been treated empirically. Conclusion: Our results suggest that EP‐guided therapy with Class IA agents is a reasonable, safe, and effective approach for the long‐term management of patients with idiopathic VF. A randomized prospective study of EP‐guided Class IA therapy in patients with ICDs seems warranted.
Characterization of Conduction in the Ventricles of Normal and Heterozygous Cx43 Knockout Mice Using Optical Mapping
Authors: MORLEY GREGORY E. , VAIDYA DHANANJAY , SAMIE FARAMARZ H. , LO CECILIA , DELMAR MARIO , JALIFE JOSÉ 
Published: April 2007

Conduction in Normal and C×43+/− Mice. Introduction: Gap junction channels are important determinants of conduction in the heart and may play a central role in the development of lethal cardiac arrhythmias. The recent development of a C×43‐deficient mouse has raised fundamental questions about the role of specific connexin isoforms in intercellular communication in the heart. Although a homozygous null mutation of the C×43 gene (C×43−/−) is lethal, the heterozygous (Cx43+/−) animals survive to adulthood. Reports on the cardiac electrophysiologic phenotype of the C×43+/− mice are contradictory. Thus, the effects of a null mutation of a single C×43 allele require reevaluation. Methods and Results: High‐resolution video mapping techniques were used to study propagation in hearts from C×43+/− and littermate control (C×43+/+) mice. Local conduction velocities (CVs) and conduction patterns were quantitatively measured by determining conduction vectors. We undertook the characterization of ECG parameters and epicardial CVs of normal and Cx43+/− mouse hearts. ECG measurements obtained from 12 C×43+/+ and 6 C×43+/− age matched mice did not show differences in any parameter, including QRS duration (14.5 ± 0.9 and 15.7 ± 2.3 msec for C×43+/+ and C×43+/−, respectively). In addition, using a sensitive method of detecting changes in local CV, video images of epicardial wave propagation revealed similar activation patterns and velocities in both groups of mice. Conclusion: A sensitive method that accurately measures local CVs throughout the ventricles revealed no changes in C×43+/− mice, which is consistent with the demonstration that ECG parameter values in the heterozygous mice are the same as those in wild‐type mice.