bluuebunny/crossref_metadata_2025 huggingface dataset:
Autonomic Blockade Unmasks Maturational Differences in Rate‐Dependent Atrioventricular Nodal Conduction and Facilitation in the Mouse
Authors: SABA SAMIR , LONDON BARRY , GANZ LEONARD
Published: August 2010

Maturational Differences in Murine AVN Conduction. Introduction: In large animals, rate‐dependent AV nodal (AVN) properties of conduction are modulated by autonomic inputs. In this study, we investigated whether the properties of AVN conduction and facilitation are altered by autonomic blockade in the mouse and whether this effect is age dependent.

Methods and Results: Young (age 4–6 weeks; n = 11) and adult (age 8–9 months; n = 11) female mice underwent in vivo electrophysiologic testing, before and after autonomic blockade. After autonomic blockade, the adult mice had significantly longer AVN effective refractory period (AVNERP; 67 ± 14 msec vs 56 ± 4 msec, P = 0.05) and functional refractory period (AVNFRP; 81 ± 10 msec vs 72 ± 4 msec, P = 0.05). With autonomic blockade, the increase from baseline of AVN Wenckebach cycle length (ΔAVW; 1.8 ± 8.1 msec vs 8.8 ± 3.3 msec, P = 0.04), as well as of AVNERP (ΔAVNERP; 3.5 ± 3.5 msec vs 21.4 ± 12.6 msec, P = 0.002) and AVNFRP (ΔAVNFRP; 2.3 ± 3.2 msec vs 12.8 ± 9.0 msec, P = 0.008), was significantly larger in adult than in young mice. Compared with young mice, adult mice were less likely to exhibit AVN facilitation (44% vs 90%, P = 0.03) and had smaller maximal shortening of AVN conduction times after the “test beat” for any coupling of the “facilitating beat” (4 ± 4 msec vs 7 ± 3 msec, P = 0.05).

Conclusion: Complete autonomic blockade significantly increases AVN conduction times and refractory periods in adult but not in young mice. Adult mice also exhibit less AVN facilitation. Our results confirm that, like in larger animals, rate‐dependent murine AVN properties of conduction are under autonomic regulation. Adult mice have higher sympathetic AVN inputs at baseline, leading to slower conduction after autonomic blockade. (J Cardiovasc Electrophysiol, Vol. 14, pp. 191‐195, February 2003)
Effect of Heating on Pulmonary Veins:
Authors: KOK LAI CHOW , EVERETT THOMAS H. , AKAR JOSEPH G. , HAINES DAVID E.
Published: August 2010

Introduction: The success of radiofrequency energy catheter ablation for the treatment of patients with paroxysmal or chronic atrial fibrillation has been complicated by postablation development of pulmonary vein (PV) stenosis. The acute effect of heat on PV structure has not been well characterized. The aim of this study was to characterize the effects of hyperthermic exposure on PVs and to determine the critical temperature at which PV stenosis would be observed.

Methods and Results: The main PVs of acutely explanted canine hearts were identified, isolated, and dissected from the left atria. Measurements of the diameter of 3‐mm PV rings were obtained at baseline and after hyperthermic exposure at 60°C, 65°C, 70°C, and 80°C. Mechanical behavior of PVs was studied by examining the stress‐strain relationship of each PV specimen after heat exposure at different temperature settings. Twenty‐eight PVs samples from 15 dogs (1–3 PVs/dog) were obtained and had a mean circumference of

8.7 ± 2.3 mm

at baseline. After heating to 60°C, 65°C, 70°C, and 80°C, the mean PV circumference was

9.2 ± 2.3 mm

(P = NS vs baseline),

6.8 ± 2.3 mm (P < 0.0001), 4.2 ± 1.5 mm (P < 0.0001)

, and

4.2 ± 0.8 mm (P < 0.0001)

, respectively. The stress‐strain curves of PV specimens were shifted to the left upon exposure to higher temperatures, indicating loss of compliance of PVs due to heat exposure. Histology showed loss of typical collagen matrix above 60°C.

Conclusion: Significant acute heat‐induced contraction of PVs at zero‐tension state was observed between 60°C and 65°C. This change was associated with collagen denaturation.
(J Cardiovasc Electrophysiol, Vol. 14, pp. 250‐254, March 2003)
Discrepancies Between the Upper Limit of Vulnerability and Defibrillation Threshold:
Authors: Gurevitz Osnat T. , Friedman Paul A. , Glikson Michael , Trusty Jane M. , Ballman Karla V. , Rosales Ana G. , Hayes David L. , Hammill Stephen C. , Swerdlow Charles D.
Published: August 2010

Introduction: Upper limit of vulnerability (ULV) has a strong correlation with defibrillation threshold (DFT) in patients with implantable cardioverter defibrillators (ICDs). Significant discrepancies between ULV and DFT are infrequent. The aim of this study was to characterize patients with such discrepancies.

Methods and Results: The ULV and DFT were determined in 167 ICD patients. Univariate and multivariate analyses were used to evaluate clinical predictors of a significant difference (≥10 J) between ULV and DFT. Only 8 patients (5%) had ≥10 J difference. ULV exceeded DFT in all of them. Absence of coronary artery disease (6/8 vs 48/159 patients; P = 0.05) and absence of documented ventricular arrhythmias (4/8 vs 12/159 patients; P = 0.01) were the only independent predictors of a significant ULV‐DFT discrepancy.

Conclusion: Significant discrepancies between ULV and DFT occur in 5% of patients with ICDs. Absence of coronary disease and documented ventricular arrhythmias predict such a discrepancy. At ICD implant, DFT testing is recommended in these patients and in patients with a high (>20 J) ULV before first‐shock energy and the need for lead repositioning are determined. (J Cardiovasc Electrophysiol, Vol. 14, pp. 728‐732, July 2003)
Pulmonary Vein Disconnection Using the LocaLisa Three‐Dimensional Nonfluoroscopic Catheter Imaging System
Authors: Macle Laurent , Jaïs Pierre , Scavée Christophe , Weerasooriya Rukshen , Hocini Mélèze , Shah Dipen C. , Raybaud Florence , Choi Kee‐Joon , Clémenty Jacques , Haïssaguerre Michel
Published: August 2010

Introduction: Catheter ablation for atrial fibrillation (AF) is associated with prolonged fluoroscopy times. We prospectively evaluated the use of the LocaLisa three‐dimensional nonfluoroscopic catheter imaging system with the aim of reducing fluoroscopy times during pulmonary vein (PV) disconnection.

Methods and Results: Fifty‐two patients with AF (47 men and 5 women, mean age 53 ± 9 years) underwent disconnection of all four PVs guided by a circumferential mapping catheter. The LocaLisa navigation system was used for real‐time three‐dimensional nonfluoroscopic imaging of the circumferential mapping catheter and ablation catheter electrodes in 26 patients. Procedural parameters were compared with those of a control group consisting of 26 patients in whom only standard fluoroscopy was used. PV disconnection was performed similarly in both groups by circumferential ablation around the ostia, with the endpoint of disconnecting left atrium to PV breakthroughs. The cumulative duration of radiofrequency (RF) energy delivery, procedural time, and fluoroscopy time required for PV disconnection were compared. Successful disconnection was achieved in all PVs, without acute complications. There was no significant difference in cumulative RF energy delivery: 34.8 ± 11.4 minutes for the nonfluoroscopic imaging group versus 38.2 ± 10.5 minutes for the control group. The fluoroscopy time required for disconnection of all four PVs was significantly lower in the LocaLisa group than in the control group: 8.4 ± 4.3 minutes versus 23.7 ± 9.7 minutes (P < 0.0001). There also was a significant difference in the mean time taken for PV disconnection: 46.5 ± 12.0 minutes for the nonfluoroscopic imaging group versus 66.3 ± 18.9 minutes for the control group (P < 0.0001).

Conclusion: By allowing continuous three‐dimensional monitoring of ablation and mapping catheter position and orientation, the LocaLisa nonfluoroscopic imaging system significantly reduces fluoroscopy and PV disconnection times. (J Cardiovasc Electrophysiol, Vol. 14, pp. 693–697, July 2003)
Ventricular Filling Slows Epicardial Conduction and Increases Action Potential Duration in an Optical Mapping Study of the Isolated Rabbit Heart
Authors: Sung Derrick , Mills Robert W. , Schettler Jan , Narayan Sanjiv M. , Omens Jeffrey H. , McCulloch Andrew D.
Published: August 2010

Introduction: Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear.

Methods and Results: Changes in action potential propagation and repolarization with increased left ventricular end‐diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 ± 0.004 in the muscle fiber direction and 0.032 ± 0.006 in the cross‐fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%± 3% (P < 0.0001) and correspondingly decreased average apparent surface conduction velocity by 16%± 7% (P = 0.007). Ventricular loading did not significantly alter action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 ± 7 msec to 207 ± 5 msec (P < 0.0001). The dispersion of APD20 was decreased with loading from 19 ± 2 msec to 13 ± 2 msec (P = 0.024), whereas the dispersion of APD80 was not significantly changed. These electrophysiologic changes with ventricular loading were not affected by the nonspecific stretch‐activated channel blocker streptomycin (200 μM) and were not attributable to changes in myocardial perfusion or the presence of an electromechanical decoupling agent (butanedione monoxime) during optical mapping.

Conclusion: Acute loading of the left ventricle of the isolated rabbit heart decreased apparent epicardial conduction velocity and increased action potential duration by a load‐dependent mechanism that may not involve stretch‐activated channels. (J Cardiovasc Electrophysiol, Vol. 14, pp. 739‐749, July 2003)
Rotors and Spiral Waves in Atrial Fibrillation
Authors: Jalife José
Published: August 2010

Despite many years of research, the mechanisms of atrial fibrillation (AF) are still poorly understood, and we currently are unable to adequately treat most patients with AF. Recently, the demonstration in both human and animal studies that the pulmonary veins (PVs) and the posterior left atrial (LA) wall play a substantial role in triggering and in driving the fibrillatory activity has opened new avenues for research into the mechanisms of initiation and maintenance AF at many levels of integration. This article focuses on recent studies at the whole‐heart level that support the hypothesis that maintenance of AF, whether paroxysmal or persistent, may depend on the periodic activity of a small number of rotors in the posterior LA wall‐PV region. These rotors activate the atria at exceedingly high frequencies and result in fibrillatory conduction. Recent clinical studies involving either segmental PV isolation or circumferential PV ablation support this view. Such encouraging results suggest that collaboration between basic and clinical electrophysiologists will lead to a more precise understanding of the manner in which rotors stabilize in the PV‐LA junction, which should open new doors for the development of innovative approaches for the prevention, diagnosis, and treatment of AF. (J Cardiovasc Electrophysiol, Vol. 14, pp. 776‐780, July 2003)
T‐Type Calcium Current in Electrical Activity of Cardiomyocytes Isolated from Rabbit Pulmonary Vein
Authors: CHEN YAO‐CHANG , CHEN SHIH‐ANN , CHEN YI‐JEN , TAI CHING‐TAI , CHAN PAUL , LIN CHENG‐I
Published: August 2010

Introduction: Pulmonary veins (PVs) are known to initiate paroxysmal atrial fibrillation. T‐type calcium current (ICa‐T) has a role in normal and abnormal automaticity of cardiomyocytes. The aim of this study was to evaluate whether ICa‐T contributes to PV electrical activity.

Methods and Results: By whole‐cell clamp techniques in rabbit myocytes, ICa‐T was identified in 12 (39%) of 31 PV cardiomyocytes with pacemaker activity, 2 (9%) of 23 PV cardiomyocytes without pacemaker activity, and 2 (15%) of 13 atrial myocytes (P < 0.05). Maximum ICa‐L and ICa‐T densities from PV cardiomyocytes with pacemaker activity were 6.87 ± 2.17 pA/pF and 1.38 ± 0.69 pA/pF, respectively. Nickel (40 μM) decreased the spontaneous activity in 5 (36%) of 14 PV cardiomyocytes (3.1 ± 0.6 Hz vs 2.2 ± 0.5 Hz, P < 0.05), reduced the amplitudes of delayed afterdepolarization from 13 ± 1 mV to 7 ± 1 mV (n = 4, P < 0.05) and inhibited transient inward currents from 1.2 ± 0.2 pA/pF to 0.7 ± 0.1 pA/pF (n = 11, P < 0.01).

Conclusions: We conclude that ICa‐T contributes to PV pacemaker activity and triggered activity, which are of functional importance in PV arrhythmogenesis. (J Cardiovasc Electrophysiol, Vol. 15, pp. 567‐571, May 2004)
High‐Flow Perfusion of Sheaths for Prevention of Thromboembolic Complications During Complex Catheter Ablation in the Left Atrium
Authors: CAUCHEMEZ BRUNO , EXTRAMIANA FABRICE , CAUCHEMEZ SIMON , COSSON STÉPHANE , ZOUZOU HANANE , MEDDANE MOHAMED , D'ALLONNES LAURE REVAULT , LAVERGNE THOMAS , LEENHARDT ANTOINE , COUMEL PHILIPPE , HOUDART EMMANUEL
Published: August 2010

Introduction: Mechanisms for thromboembolic complications during complex ablation procedures in left atrium (LA) have not been defined. The aim of this study was to determine the effect of the perfusion rate of the transseptal sheath on the incidence of thromboembolic complications during catheter ablation for atrial fibrillation (AF) or LA macroreentrant tachycardia.

Methods and Results: We analyzed clinical and procedural data from 86 consecutive patients (153 procedures) referred for catheter ablation of AF (74 patients) or LA macroreentrant tachycardia (12 patients). The transseptal sheath was continuously perfused at a low flow rate (3 mL/hour) for the first 32 patients and at a high flow rate (180 mL/hour) for the subsequent 54 patients. Ablation was mainly performed using map‐guided isolation of pulmonary veins for AF and three‐dimensional electroanatomic mapping for LA macroreentrant tachycardia. Five patients (6% of patients and 3.5% of procedures) developed a cerebral thromboembolic complication, all during procedures using low‐flow perfusion. Sheath perfusion rate and total procedure duration were the two variables significantly associated with the occurrence of stroke (P = 0.013 and 0.001, respectively). After adjustment in a multivariable analysis, sheath perfusion rate remained the only risk factor for stroke. The risk was 17 times higher using low‐flow than high‐flow perfusion (odds ratio 17.26, 95% confidence interval 1.14–260.81, P = 0.04). No other clinical or procedural parameters had any significant effect.

Conclusion: Sheath perfusion rate is an important determinant of the risk factor for stroke during complex LA ablation procedures. Continuous high‐flow perfusion appears to be effective in preventing this complication. (J Cardiovasc Electrophysiol, Vol. 15, pp. 276‐283, March 2004)
Fractionation of Electrograms and Linking of Activation During Pharmacologic Cardioversion of Persistent Atrial Fibrillation in the Goat
Authors: SHAN ZHAOLIANG , VAN DER VOORT PEPIJN H. , BLAAUW YURI , DUYTSCHAEVER MATTIAS , ALLESSIE MAURITS A.
Published: August 2010

Introduction: During atrial fibrillation (AF), there is fractionation of extracellular potentials due to head‐to‐tail interaction and slow conduction of fibrillation waves. We hypothesized that slowing of the rate of AF by infusion of a Class I drug would increase the degree of organization of AF.

Methods and Results: Seven goats were instrumented with 83 epicardial electrodes on the left atrium, left atrial appendage, Bachmann's bundle, right atrium, and right atrial appendage. AF was induced and maintained by an automatic atrial fibrillator. After AF had persisted for 4 weeks, the Class IC drug cibenzoline was infused at a rate of 0.1 mg/kg/min. AF cycle length (AFCL), the percentage of fractionated potentials, conduction velocity (CV), and direction of propagation of the fibrillation waves were measured during baseline, after AFCL was increased by 20, 40, 60, and 80 ms, and shortly before cardioversion. Infusion of cibenzoline increased the mean of the median AFCLs from 96 ± 6 ms to 207 ± 43 ms (P < 0.0001). The temporal variation in AFCL in different parts of the atria was 8% to 20% during control and, with the exception of Bachmann's bundle, was not significantly reduced during cibenzoline infusion. CV decreased from 76 ± 14 ms to 52 ± 9 cm/s (P < 0.01). Cibenzoline increased the percentage of single potentials from 81%± 4% to 91%± 4% (P < 0.01) and decreased the incidence of double potentials from 14%± 4% to 7 ± 5% (P < 0.01) and multiple potentials from 5%±% to 1%± 2% (P < 0.001). Whereas during control, linking (consecutive waves propagating in the same direction) during seven or more beats occurred in 9%± 15% of the cycles, after cibenzoline the degree of linking had increased to 40%± 33% (P < 0.05). During the last two beats before cardioversion, there was a sudden prolongation in AFCL from 209 ± 37 ms to 284 ± 92 ms (P < 0.01) and a strong reduction in fractionated potentials (from 22%± 12% to 6%± 5%, P < 0.05).

Conclusion: The Class IC drug cibenzoline causes a decrease in fractionation of fibrillation electrograms and an increase in the degree of linking during AF. This supports the observation that Class I drugs widen the excitable gap during AF. (J Cardiovasc Electrophysiol, Vol. 15, pp. 572‐580, May 2004)
Atrial Activation Mapping in Sinus Rhythm in the Clinical Electrophysiology Laboratory:
Authors: COSÍO FRANCISCO G. , MARTÍN‐PEÑATO ARTURO , PASTOR AGUSTÍN , NÚÑEZ AMBROSIO , MONTERO MARÍA ANTONIA , CANTALE CARINA P. , SCHAMES SALOMAO
Published: August 2010

Introduction: The high posterolateral right atrium (RA) is considered the “sinus node area,” but we lack information on endocardial atrial activation in sinus rhythm. We studied RA and left atrial (LA) endocardial activation in the electrophysiology laboratory.

Methods and Results: Thirty‐five patients (21 men) aged 47 ± 16.4 years (mean ± SD) underwent RA mapping (22.2 ± 3.8 points). In 21 patients, LA activation was mapped (11.1 ± 3.9 points) through the coronary sinus (CS), right pulmonary artery, and/or a patent oval foramen. Fourteen patients had atrial arrhythmias, and 3 an ECG pattern of Bachmann's bundle block. Endocardial RA activation preceded P wave in 5 (–14 ± 4.2 ms), coincided in 11, and followed P onset in 18 (16.7 ± 6.6 ms). Location of the zero point varied from the superior vena cava to the low RA and from lateral to paraseptal RA. In 19 patients, activation started simultaneously in 2 to 5 points located ≥1 cm apart. RA activation was descending in most, but in 3 with low onset there was collision in the anterior and septal walls. In 15 of 21 patients, descending LA activation dominated, ending in the mid CS in 12, proximal CS in 1, and simultaneously throughout the CS in 2. In 3 with Bachmann's bundle block, CS activation was ascending and in 2 double potentials were recorded from the LA roof.

Conclusion: During stable sinus rhythm, RA activation can start in different areas or simultaneously over large areas resulting in different activation patterns, both in the RA and the LA. LA activation is predominantly descending, but in Bachmann's bundle block it becomes ascending, and double potentials suggest a location of block in the LA roof. (J Cardiovasc Electrophysiol, Vol. 15, pp. 524‐531, May 2004)
Cryoenergy Catheter Ablation:
Authors: GAITA FIORENZO , ANTONIO MONTEFUSCO , RICCARDI RICCARDO , GIUSTETTO CARLA , GROSSI STEFANO , CARUZZO ENRICO , BIANCHI FRANCESCA , VIVALDA LAURA , GABBARINI FULVIO , CALABRO RAFFAELE
Published: August 2010

Introduction: Permanent junctional reciprocating tachycardia (PJRT) is an infrequent form of reciprocating tachycardia, almost incessant from childhood and usually refractory to drug therapy. Radiofrequency catheter ablation currently is the first‐line therapy for PJRT, but its application in the septal region may be associated with complications. In contrast, cryoenergy has several advantages, such as the ability to test the effects of ablation while the lesion is still forming, thus reducing the number of ineffective, useless, and potentially harmful lesions. The aim of this study was to investigate the potential clinical utility of percutaneous cryoenergy catheter ablation for treatment of pediatric patients with PJRT.

Methods and Results: Four patients (age 14 ± 5 years; mean ± SD) with a clinical diagnosis of PJRT underwent catheter cryoablation. The ablation was successfully accomplished in 4 (100%) of 4 patients. The mean ± SD number of cryoapplications was 1.8 ± 0.8, and from 1 to 6 cryomappings were performed for each permanent cryolesion. The successful site was in the mid‐septal region (2 patients), at the coronary sinus orifice (1 patient), and in the middle cardiac vein (1 patient). No complications with cryoablation were reported, nor was there prolongation of the AH interval during cryomapping or cryoablation. No pain was reported by patients during the cryoenergy catheter ablation procedure. PJRT recurrence occurred in 1 patient who underwent a second successful cryoablation procedure.

Conclusion: The outcomes of cryoenergy catheter ablation in these 4 patients treated for PJRT suggest that cryoablation is a safe, effective, and pain‐free technique for treating pediatric patients with PJRT. (J Cardiovasc Electrophysiol, Vol. 15, pp. 263‐268, March 2004)
Misdiagnosis of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
Authors: BOMMA CHANDRA , RUTBERG JULIE , TANDRI HARIKRISHNA , NASIR KHURRAM , ROGUIN ARIEL , TICHNELL CRYSTAL , RODRIGUEZ RENE , JAMES CYNTHIA , KASPER EDWARD , SPEVAK PHILIP , BLUEMKE DAVID A. , CALKINS HUGH
Published: August 2010

Introduction: Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) has major implications for the management of patients and their first‐degree relatives. Diagnosis is based on a set of criteria proposed by the International Task Force for Cardiomyopathies. We report our experience in providing a re‐evaluation for patients who previously have been diagnosed with ARVD/C.

Methods and Results: We studied 89 patients who requested a re‐evaluation for diagnosis of ARVD/C at our center. Each of these patients had been diagnosed with ARVD/C at their initial evaluation. Each patient was re‐evaluated with clinical history, physical examination, and noninvasive testing at our center. Invasive testing, which included electrophysiologic testing, right ventricular angiography, and endomyocardial biopsy, was performed when clinically indicated. Sixty (92%) of the 65 patients who had undergone magnetic resonance imaging (MRI) at an outside institution were reported to have an abnormal MRI consistent with ARVD/C. Among these patients, the only abnormality identified was the qualitative finding of intramyocardial fat/wall thinning in 46 patients. On re‐evaluation, these qualitative findings were not confirmed. None of these 46 patients ultimately were diagnosed with ARVD/C. Among the entire patient group, only 24 (27%) of the 89 patients met the Task Force criteria for ARVD/C.

Conclusion: This study demonstrates that the high frequency of “misdiagnosis” of ARVD/C is due to over‐reliance on the presence of intramyocardial fat/wall thinning on MRI, incomplete diagnostic testing, and lack of awareness of the Task Force criteria. Diagnosis of ARVD/C cannot rely solely upon qualitative features on MRI. (J Cardiovasc Electrophysiol, Vol. 15, pp. 300‐306, March 2004)
Activation of the Ca2+‐Activated Nonselective Cation Channel by Diacylglycerol Analogues in Rat Cardiomyocytes
Authors: GUINAMARD ROMAIN , CHATELIER AURÉLIEN , LENFANT JACQUES , BOIS PATRICK
Published: August 2010

Introduction: Cardiac hypertrophy is associated with changes in electrophysiologic properties due to ionic channel modifications and increases in protein kinase C (PKC) activity and diacylglycerol (DAG) content. These changes may contribute to an increased propensity for arrhythmia. Similar electrophysiologic modifications have been reported in adult rat cardiomyocytes undergoing dedifferentiation in primary culture.

Methods and Results: Single‐channel measurements on such cells identified the appearance of a Ca2+‐activated nonselective cation channel (NSCCa) during the dedifferentiation process. The current study investigated the sensitivity of this channel to PKC and DAG analogues. In the cell‐attached configuration, channel conductance was 20.2 pS under physiologic conditions. Perfusion with the DAG analogue 1‐oleoyl‐2‐acetyl‐sn‐glycerol (OAG, 0.1 mM) or the PKC activator phorbol 12‐myristate 13‐acetate (PMA, 0.5 μM) increased the channel normalized open probability (nPo), whereas in the presence of the PKC inhibitor calphostin C (1 μM), only OAG retained this effect. In the inside‐out configuration, perfusion of both DAG analogues OAG (0.1 mM) and 1‐stearoyl‐2‐arachidonoyl‐sn‐glycerol (SAG, 10 μM) on the inside of the membrane increased nPo. These results indicate that DAG regulates the NSCCa channel via both the PKC pathway and by a direct interaction.

Conclusion: DAG content, PKC activity, and channel expression increased during hypertrophy. This indicates that the NSCCa channel exhibits high activity in this condition and, therefore, is a candidate for the genesis of arrhythmias in ventricular cardiomyocytes. In addition, regulation of the channel by DAG and PKC contributes to current understanding of the physiologic role of this channel, which shares properties with the cloned TRPM4b channel. (J Cardiovasc Electrophysiol, Vol. 15, pp. 342‐348, March 2004)
Embryonic Conduction Tissue:
Authors: JONGBLOED MONIQUE R.M. , SCHALIJ MARTIN J. , POELMANN ROBERT E. , BLOM NICO A. , FEKKES MADELON L. , WANG ZHIYONG , FISHMAN GLENN I. , GITTENBERGER‐DE GROOT ADRIANA C.
Published: August 2010

Introduction: The occurrence of arrhythmias in adult patients may arise preferentially in anatomic regions derived from the specialized cardiac conduction system. To examine this hypothesis, we performed a detailed analysis of the developing cardiac conduction system using the recently described CCS‐lacZ transgenic mouse strain.

Methods and Results: Transgenic embryos (E9.5–15.5) were stained for β‐galactosidase activity and co‐stained with the myocardial marker HHF35. Results were reconstructed three dimensionally. CCS‐lacZ expression was observed in the sinoatrial node, left and right venous valves, septum spurium, right and left atrioventricular ring, His bundle, bundle branches, and right ventricular moderator band. Furthermore, lacZ‐positive cells could be demonstrated for the first time in the left atrium, in the posterior wall surrounding the pulmonary venous orifice. and, in later stages, surrounding the pulmonary venous wall. These cells were continuous with the left venous valve in the right atrium. LacZ‐positive tissue also could be identified in Bachmann's bundle, running retro‐aortically between the right atrium and left atrium.

Conclusion: Known arrhythmogenic areas including Bachmann's bundle, the pulmonary veins, and sinus venosus derived internodal structures, demonstrate lacZ expression. These data support the hypothesis that areas derived from the developing cardiac conduction system may contribute to the arrhythmogenic substrate in adult hearts. (J Cardiovasc Electrophysiol, Vol. 15, pp. 349‐355, March 2004)
Spatial Dispersion of Repolarization is a Key Factor in the Arrhythmogenicity of Long QT Syndrome
Authors: RESTIVO MARK , CAREF EDWARD B. , KOZHEVNIKOV DMITRY O. , EL‐SHERIF NABIL
Published: August 2010

Introduction: The occurrence of significant spatial dispersion of repolarization in vivo as it relates to the mechanism of arrhythmia formation in the long QT syndrome (LQTS) continues to be questioned.

Methods and Results: We investigated a guinea pig model of LQT3 using anthopleurin‐A (AP‐A) to study the contribution of rate‐dependent spatial dispersion of repolarization in the intact heart to the arrhythmogenicity of LQTS. Optical action potentials were measured using potentiometric fluorescent dye di‐4ANEPPS in Langendorff‐perfused hearts with induced AV block. AP‐A exacerbated the normal uniform epicardial apex‐base action potential duration (APD) gradient, resulting in rate‐dependent increased APD dispersion and nonuniform APD gradient. Spontaneous focal premature beats induced functional conduction block along boundaries where large nonuniform APD gradient occurred setting the stage for circulating wavefronts and ventricular tachyarrhythmia (VT). Endocardial ablation abolished spontaneous VT, but nonuniform epicardial APD gradient persisted and could be challenged by a stimulated premature stimulus to induce VT.

Conclusion: The study shows that in LQT3, spatial variations in steady‐state properties result in zones of nonuniform APD gradients. These provide a substrate for functional conduction block and reentrant excitation when challenged by subendocardial “early afterdepolarization‐triggered” premature beats. The study emphasizes the key importance of spatial dispersion of repolarization, whether located in epicardial or intramyocardial layers, in arrhythmia formation in LQTS. (J Cardiovasc Electrophysiol, Vol. 15, pp. 323‐331, March 2004)
Efficacy and Safety of Segmental Ostial Versus Circumferential Extra‐Ostial Pulmonary Vein Isolation for Atrial Fibrillation
Authors: MANSOUR MOUSSA , RUSKIN JEREMY , KEANE DAVID
Published: August 2010

Introduction: Pulmonary vein (PV) isolation for atrial fibrillation (AF) can be performed using a segmental ostial or a circumferential extra‐ostial approach. The relative merits and potential limitations of each approach are currently debated. Here we report our early experience with each of these approaches, including their relative efficacy and safety.

Methods and Results: Forty patients with drug‐refractory AF underwent segmental ostial PV isolation and were compared to 40 consecutive patients who underwent PV isolation using a circumferential extra‐ostial approach. The latter approach described here is novel in two aspects: (1) the endpoint for ablation was PV isolation and not only delay in left atrial to PV conduction time, and (2) isolation of the right and left PVs was achieved by a single encirclement of ipsilateral veins. At follow‐up, 60% of the patients in the segmental group were free of AF compared to 75% of the patients in the circumferential group. There was one thromboembolic cerebrovascular complication during the ablation procedure in each group.

Conclusion: PV isolation using a circumferential extra‐ostial approach, where the ipsilateral PVs are isolated together by one encircling line of block using electroanatomic mapping, is a technically feasible procedure. This approach is at least as effective and safe as the more established segmental ostial approach for AF ablation. (J Cardiovasc Electrophysiol, Vol. 15, pp. 532‐537, May 2004)
Superior Vena Cava Rhythm Masquerading as Normal Sinus Rhythm
Authors: YUNIADI YOGA , TAI CHING‐TAI , LIN YENN‐JANG , CHEN SHIH‐ANN
Published: August 2010

We report the case of a patient with persistent cardiac rhythm originating from the superior vena cava (3 cm above the vena cava‐atrial junction). It was detected by noncontact balloon mapping before induction of tachycardia and confirmed by conventional contact mapping with image studies. Thus, a 12‐lead ECG showing normal morphologies of P waves may not indicate that the P waves are of sinus node origin.
Atrial Fibrillatory Wave Characteristics on Surface Electrogram:
Authors: XI QIN , SAHAKIAN ALAN V. , NG JASON , SWIRYN STEVEN
Published: August 2010

Introduction: Fibrillatory waves on the surface ECG have been scrutinized to allow inferences about underlying mechanisms and pathophysiology, based on the premise that fibrillatory waves do not vary “randomly” but provide a consistent reflection of the underlying state of the atria in an individual patient. This premise is untested.

Methods and Results: Ten standard ECGs were recorded over a 24‐hour period in each of 20 clinically stable inpatients with atrial fibrillation. After QRS‐T cancellation, the remainder fibrillatory waves were analyzed. Interpatient versus intrapatient differences in fibrillatory wave characteristics were evaluated by analysis of variance (ANOVA). The fibrillatory wave peak‐to‐peak amplitude of all the patients ranged from 0.06 to 0.35 mV, whereas 1 SD of the amplitude for each patient ranged from 0.004 to 0.053 mV. Short‐term peak frequencies of all the patients ranged from 4.6 to 8.0 Hz, whereas 1 SD for each patient varied from 0.2 to 0.5 Hz. For these and all other parameters tested, interpatient differences were significantly greater compared to intrapatient differences (P < 0.0001).

Conclusion: Fibrillatory wave characteristics are repeatable from ECG to ECG over 24 hours for clinically stable patients, whereas substantial differences are present between patients. Further study of the relationship of such characteristics to pathophysiology and management decisions is valid and warranted. (J Cardiovasc Electrophysiol, Vol. 15, pp. 911‐917, August 2004)
Relationship Between QRS Duration and Left Ventricular Dyssynchrony in Patients with End‐Stage Heart Failure
Authors: BLEEKER GABE B. , SCHALIJ MARTIN J. , MOLHOEK SANDER G. , VERWEY HARRIETTE F. , HOLMAN EDUARD R. , BOERSMA ERIC , STEENDIJK PAUL , VAN DER WALL ERNST E. , BAX JEROEN J.
Published: August 2010

Introduction: Patients with end‐stage heart failure and a wide QRS complex are considered candidates for cardiac resynchronization therapy (CRT). However, 20% to 30% of patients do not respond to CRT. Lack of left ventricular dyssynchrony may explain the nonresponse. Accordingly, we evaluated the presence of left ventricular dyssynchrony using tissue Doppler imaging (TDI) in 90 consecutive patients with heart failure.

Methods and Results: Ninety patients with severe heart failure (left ventricular ejection fraction <35%, New York Heart Association class III–IV) were prospectively evaluated. Based on QRS duration, 30 consecutive patients with a narrow QRS complex were included (QRS duration ≤120 ms), 30 patients with an intermediate QRS duration (120–150 ms), and 30 patients with a wide QRS complex (>150 ms). All patients underwent TDI to assess left ventricular dyssynchrony. Extensive left ventricular dyssynchrony was defined as an electromechanical delay on TDI between the septum and lateral wall, the so‐called septal‐to‐lateral delay, of >60 ms. Severe dyssynchrony was observed in 27% of patients with narrow QRS complex, 60% with intermediate QRS duration, and 70% with wide QRS complex. No relation existed between QRS duration and septal‐to‐lateral delay.

Conclusion: From 30% to 40% of heart failure patients with QRS duration >120 ms do not exhibit left ventricular dyssynchrony, which may explain the nonresponse to CRT. Alternatively, 27% of patients with heart failure and a narrow QRS complex show significant left ventricular dyssynchrony and may be candidates for CRT. (J Cardiovasc Electrophysiol, Vol. 15, pp. 544‐549, May 2004)
Impact of Biphasic Electrical Cardioversion of Atrial Fibrillation on Early Recurrent Atrial Fibrillation and Shock Efficacy
Authors: SIAPLAOURAS STEPHANOS , BUOB AXEL , RÖTTER CARSTEN , BÖHM MICHAEL , JUNG JENS
Published: August 2010

Introduction: Early recurrent atrial fibrillation (ERAF) after external cardioversion of atrial fibrillation (AF) occurs in 12% to 26% of patients. Whether biphasic cardioversion has an impact on the incidence of ERAF after cardioversion of AF is unclear.

Methods and Results: Consecutive patients (n = 216, mean age 66 years, 71% male, 88% with structural cardiovascular disease or hypertension) underwent cardioversion with a biphasic (Bi) or monophasic (Mo) shock waveform in randomized fashion. Energies used were 120‐150‐200‐200 Ws (Bi) or 200‐300‐360‐360 Ws (Mo). The two study groups (Bi vs Mo) did not differ with regard to age, sex, body mass index, underlying cardiovascular disease, left atrial diameter, left ventricular ejection fraction, duration of AF fibrillation, and antiarrhythmic drug therapy. Mean delivered energy was significantly lower in the Bi group (Bi: 186 ± 143 Ws vs Mo: 324 ± 227 Ws; P < 0.001). Overall incidence of ERAF (AF relapse within 1 minute after successful cardioversion) was 8.9% and showed no difference between the two groups (Bi: 8.1% vs Mo: 9.7%, P = NS). Cardioversion was successful in 95.4% of patients. The success rate was comparable in both groups (Bi: 94.3% vs Mo 96.8%; P = NS). First shock efficacy did not differ between Bi and Mo (76.4% vs 67.7%; P = NS). Mean number of shocks were 1.4 shocks per patient in both groups.

Conclusion: Biphasic cardioversion allows comparable success rates with significantly lower energies. However, the incidence of ERAF is not influenced by biphasic cardioversion. With the energies used, biphasic and monophasic shock waveforms are comparable with regard to first shock and cmulative shock efficacy.
Myocardial Ischemia and Induction of Sustained Ventricular Tachyarrhythmias:
Authors: STAMBLER BRUCE S. , AKOSAH KWAME O. , MOHANTY PRAMOD K. , WOOD MARK A. , ELLENBOGEN KENNETH A.
Published: August 2010

Introduction: This study examined the relationship between dobutamine facilitation of ventricular tachyarrhythmia (VT) inducibility with programmed electrical stimulation (PES) and dobutamine stress‐induced myocardial ischemia.

Methods and Results: Twenty patients with prior myocardial infarction and cardiac arrest or sustained VT but no sustained VT induced at baseline electrophysiologic testing underwent repeat PES during dobutamine infusion. Ischemia (new or worsened wall‐motion abnormality) was documented by echocardiography performed in conjunction with PES. Eight patients were receiving Class I or III antiarrhythmic drugs and seven beta‐blockers. Dobutamine facilitated induction of sustained VT in 16 patients (80%) and provoked ischemia in 13 patients (65%). Induction of VT was associated with ischemia in 9 patients (56%). VTs associated with ischemia were induced at higher dobutamine doses (26 ± 11 vs 11 ± 10 μg/kg per min, P = 0.02) than were VTs without ischemia (n = 7). Among 13 patients with provoked ischemia, 9 (69%) had VTs induced and 4 remained noninducible. The onset of ischemia occurred at the same dose as induction of VT in 5 patients and at a lower dose in 4 patients. Monomorphic VT (318 ± 59 ms) was induced in 13 patients, of whom 8 (62%) had ischemia. The ECG morphology of VT suggested an origin in a myocardial segment that demonstrated initial viability at low doses then ischemic dysfunction at higher doses preceding VT induction in 7 (88%) of 8 patients.

Conclusion: Dobutamine enhances inducibility of sustained VTs during PES. The temporal and anatomic association of dobutamine‐induced ischemia and VT suggests that at high dobutamine doses, ischemia may contribute to ventricular arrhythmia inducibility in some patients.
Delayed Afterdepolarization‐Mediated Triggered Activity Associated with Slow Calcium Sequestration Near the Endocardium
Authors: LAURITA KENNETH R. , KATRA RODOLPHE P.
Published: August 2010

Introduction: Previously, we have shown that cells near the endocardium are more prone to elevated diastolic intracellular calcium levels than cells near the epicardium. The arrhythmogenic consequence of such regional differences in calcium handling is not clear.

Methods and Results: Using optical mapping techniques, calcium transients and action potentials were recorded simultaneously from ventricular sites across the transmural wall of the arterially perfused canine left ventricular wedge preparation during control conditions, and under conditions of increased calcium entry (IK blockade and β‐adrenergic stimulation). Under conditions of enhanced calcium entry, the decay of the calcium transient and diastolic calcium levels during rapid pacing were slower (38%, P < 0.01) and higher (215%, P < 0.02), respectively, near (within ∼3 mm) the endocardium compared to the epicardium (n = 9). Immediately after termination of rapid pacing under conditions of increased calcium entry, ectopic activity and simultaneous delayed afterdepolarizations and spontaneous calcium release events were observed. Over all experiments, ectopic activity occurred more frequently closer to the endocardium compared to the epicardium.

Conclusions: Under conditions of enhanced calcium entry, myocytes closer to the endocardium exhibit a higher level of diastolic calcium and greater ectopic activity compared to the epicardium. We show for the first time simultaneous delayed afterdepolarization and spontaneous calcium release events from myocytes in a normally coupled multicellular preparation. These data combined suggest that myocytes near the endocardium are more susceptible to calcium‐mediated triggered activity.
Regional Variation in Capture of Fibrillating Swine Left Ventricle During Electrical Stimulation
Authors: NANTHAKUMAR KUMARASWAMY , JOHNSON PHILLIP L. , HUANG JIAN , KILLINGSWORTH CHERYL R. , ROLLINS DENNIS L. , MCELDERRY HUGH T. , SMITH WILLIAM M. , IDEKER RAYMOND E.
Published: August 2010

Introduction: While it has been shown that electrical stimulation can capture a region of myocardium during ventricular fibrillation (VF), the ideal location to stimulate to maximize capture of the fibrillating in vivo left ventricle (LV) is not known. We previously demonstrated a mean directionality to the propagation of VF wavefronts in swine from posterior to anterior LV. We hypothesized that this directionality of VF wavefronts would affect capture of the LV epicardium while stimulating during VF.

Methods and Results: In seven open‐chest swine, during different VF episodes, electrical stimulation was performed singly or simultaneously from two lines of 26 epicardial electrodes, one on the posterior LV adjacent to the posterior descending coronary artery and another on the anterior LV adjacent to the left anterior descending coronary artery. Mapping was performed between the line of stimulating electrodes with 768 recording electrodes 2‐mm apart. The incidence and extent of epicardium captured by stimulation through the lines of stimulating electrodes were determined in the mapped region. Capture occurred during 67% of 78 VF episodes. Capture from the posterior LV line was achieved in 88% of the episodes and from the anterior LV line in 44% of the episodes (P = 0.001). The maximum amount of myocardium captured was also much greater for stimulating from the posterior as compared to the anterior LV line (232 ± 168 mm2 vs 64 ± 124 mm2, P = 0.003). A significant part of the variability in capture was related to the direction of the mean VF wavefront velocity vector in each animal (r = 0.84, P < 0.05).

Conclusion: Electrical stimulation from the posterior LV resulted in a greater incidence and extent of LV capture than stimulation from the anterior LV. A significant component of the variability in capture is related to the mean direction of VF wavefronts.
Cardiac Resynchronization Therapy: Retiming the Failing Right Ventricle
Authors: COWBURN PETER J. , PARKER JOHN D. , CAMERON DOUGLAS A. , HARRIS LOUISE
Published: August 2010

Cardiac resynchronization therapy (CRT) improves symptoms, reduces hospitalization, and may decrease mortality in patients with moderate/severe heart failure and left bundle branch block. Whether CRT may have a role in the management of patients with adult congenital heart disease and a failing right (systemic) ventricle is unknown. We report the case of an adult patient with transposition of the great arteries and previous Mustard's repair, who successfully underwent CRT using a hybrid transvenous/epicardial approach. Exercise tolerance improved, right ventricular (systemic) ejection fraction improved, diuretic requirements reduced, and renal function improved. CRT may offer a new therapeutic option for this patient population.
Automatic Impedance Monitoring and Patient Alert Feature in Implantable Cardioverter Defibrillators:
Authors: DURU FIRAT , LUECHINGER ROGER , SCHARF CHRISTOPH , BRUNCKHORST CORINNA
Published: August 2010

Recent advances in implantable cardioverter defibrillator (ICD) technology have enabled implementation of an automatic monitoring feature in ICDs that provides daily measurements of several technical parameters such as battery status, pacing, and high‐voltage impedance. The system alerts the patient with an audible alarm to contact the physician in case the measured parameters are not within normal limits. Early detection of intermittent and potentially serious complications justifies routine use of this feature. This report describes a patient with an ICD who died suddenly due to ventricular fibrillation, which was not appropriately treated by the device. The cause of device malfunction was most likely an intermittent lead fracture that was not detected by the automatic impedance monitoring and alert feature of this device. Based on these data, potential benefits and theoretical pitfalls of automatic impedance monitoring and alert features are discussed.
Clinical and Electrophysiological Characteristics of Brugada Syndrome Caused by a Missense Mutation in the S5‐Pore Site of SCN5A
Authors: ITOH HIDEKI , SHIMIZU MASAMI , MABUCHI HIROSHI , IMOTO KEIJI
Published: August 2010

Brugada syndrome is an inherited cardiac disorder caused by mutations in the SCN5A gene encoding the cardiac sodium channel α‐subunit, and potentially leads to ventricular fibrillation and sudden death. We report a case of a novel SCN5A mutation associated with Brugada syndrome. A 51‐year‐old man suffered from recurrent nocturnal syncopal attacks due to polymorphic ventricular tachycardia. His electrocardiogram showed ST‐segment elevation in V1–V3 leads, but there was no evidence of structural heart disease. DNA sequence analysis of SCN5A in this patient revealed a missense mutation (R282H) in the S5‐pore region of domain I. This mutational change was not present in 100 healthy Japanese controls. In the patient's family, a 36‐year‐old brother had died suddenly. Genetic analysis identified two other carriers of the R282H mutation, who had ST‐segment elevation and slightly increased QRS widths, but they experienced no syncopal episodes or ventricular fibrillation. Electrophysiological investigation of the R282H mutant channel expressed in cultured cells showed a severe reduction in sodium current density and a mild positive shift of activation curve. R282H did not enhance intermediate inactivation. Single‐channel conductance of R282H was slightly decreased compared with WT. The electrophysiological characteristics of the R282H channel are suggested to be closely related to the clinical phenotype of Brugada syndrome.