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We describe a novel approach for simultaneously determining regional differences in action potential (AP) morphology and tissue electrophysiological properties in isolated atria. The epicardial surface of rat atrial preparations was placed in contact with a multi-electrode array (9 × 10 silver chloride electrodes, 0.1 mm diameter and 0.1 mm pitch). A glass microelectrode (100 MΩ) was simultaneously inserted into the endocardial surface to record intracellular AP from either of 2 regions (A, B) during pacing from 2 opposite corners of the tissue. AP duration at 80% of repolarisation and its restitution curve was significantly different only in region A (p < 0.01) when AP was initiated at different stimulation sites. Alternans in AP duration and AP amplitude, and in conduction velocity were observed during 2 separate arrhythmic episodes. This approach of combining microelectrode array and intracellular membrane potential recording may provide new insights into arrhythmogenic mechanisms in animal models of cardiovascular disease.

There is a known association between obstructive sleep apnea (OSA) and atrial fibrillation (AF); however, how OSA affects the atrial myocardium is not well described.To determine whether patients with OSA have an abnormal atrial substrate.Forty patients undergoing ablation of paroxysmal AF and in sinus rhythm (20 with OSA [apnea-hypopnea index ≥ 15] and 20 reference patients with no OSA [apnea-hypopnea index15] by polysomnography) were studied. Multipolar catheters were positioned at the lateral right atrium (RA), coronary sinus, crista terminalis, and RA septum to determine the effective refractory period at 5 sites, conduction time along linear catheters at the RA and the coronary sinus, conduction at the crista terminalis, and sinus node function (corrected sinus node recovery time). Biatrial electroanatomic maps were created to determine the voltage, conduction, and distribution of complex electrograms (duration ≥ 50 ms).The groups had no differences in the prevalence of established risk factors for AF. Patients with OSA had the following compared with those without OSA: no difference in effective refractory period (P = .9), prolonged conduction times along the coronary sinus and RA (P = .02), greater number (P = .003) and duration (P = .03) of complex electrograms along the crista terminalis, longer P-wave duration (P = .01), longer corrected sinus node recovery time (P = .02), lower atrial voltage (RA, P.001; left atrium, P.001), slower atrial conduction velocity (RA, P = .001; left atrium, P = .02), and more widespread complex electrograms in both atria (RA, P = .02; left atrium, P = .01).OSA is associated with significant atrial remodeling characterized by atrial enlargement, reduction in voltage, site-specific and widespread conduction abnormalities, and longer sinus node recovery. These features may in part explain the association between OSA and AF.

Patients with lone atrial fibrillation (AF) have an abnormal atrial substrate.The purpose of this study was to determine the role of direction-dependent conduction in patients with lone AF.Twenty-four patients with paroxysmal lone AF and 24 reference patients with left-sided accessory pathways were studied. Multipolar catheters placed at the lateral right atrium, crista terminalis, coronary sinus (CS), and left atrial roof were used to determine direction-dependent conduction characteristics. Biatrial electroanatomic maps were created during sinus rhythm and with distal CS pacing to characterize direction-dependent differences in conduction velocities, electrogram complexity, and voltage.Differing wavefront directions caused changes in conduction velocity (P.001), biatrial activation times (P.001), electrogram fragmentation (P.001), site-specific conduction delays (P.001), and voltage (P.001) in both lone AF and reference patients. These direction-dependent abnormalities were amplified in lone AF patients compared to reference patients, who exhibited greater slowing in conduction velocities (P = .02), prolongation of biatrial activation time (P = .04), increase in number (P.001) and length (P.001) of lines of conduction block, increase in proportion of fractionated electrograms (P.001), and decrease in voltage (P = .03) during distal CS pacing compared to sinus rhythm.This study demonstrates the marked direction-dependent conduction abnormalities present in patients with lone AF. These results provide further insights into the critical interplay between the underlying abnormal substrate and differing wavefront directions. The study suggests that direction-dependent conduction abnormalities may explain in part the greater arrhythmogenicity of ectopic triggers from the left atrium rather than the right atrium.

1. High-density cardiac electrophysiological study (EPS) of small animal atria has been limited to optical mapping techniques, which require complex and expensive equipment setup. We aim to evaluate the feasibility of carrying out EPS in isolated atrial tissues using a custom made high-density multiple-electrode array (MEA). 2. Isolated rat atrial preparations were studied. The MEA (4 × 5 mm) consisted of 90 silver chloride coated electrodes (0.1 mm diameter, 0.5 mm pitch) and was connected to a conventional EP system yielding 80 bipolar signals. Atrial tissues were placed over the MEA in a dish bubbled with 100% oxygen and superfused with modified HEPES solution at pH 7.35 and 37°C. Then, 1 mmol of 2,3-butanedione monoxime was added to suppress motion artifacts from muscle contractions. Custom plaque analysis software was used for offline conduction analysis. 3. Isolated atrial tissues showed good viability of > 30 min, allowing ample time for complete EPS. High quality electrograms with excellent signal to noise ratio were obtained. All electrophysiological parameters showed good reproducibility: effective refractory period, conduction velocity and heterogeneity index. Tachycardia was also inducible in these normal atria. 4. The present study shows the feasibility of performing high-density EPS of small isolated atrial tissues with a conventional electrode-based technique. The MEA system is compatible with standard electrophysiology recording systems and provides a novel, inexpensive option for detailed EPS in small animal models. In particular, it presents new research avenues to further explore the mechanisms of atrial arrhythmias in various transgenic and knockout rodent models.

Objectives The purpose of this study was to determine whether patients with paroxysmal “lone” atrial fibrillation (AF) have an abnormal atrial substrate. Background While “AF begets AF,” prompt termination to prevent electrical remodeling does not prevent disease progression. Methods Twenty-five patients with paroxysmal lone AF, without arrhythmia in the week prior, and 25 reference patients with left-sided accessory pathways were studied. Multipolar catheters placed at the lateral right atrium (RA), crista terminalis, coronary sinus, septal RA, and sequentially within the left atrium (LA) determined the effective refractory period (ERP) at 10 sites, conduction time along linear catheters, and conduction characteristics at the crista terminalis. Bi-atrial electroanatomic maps were created to determine regional differences in conduction velocity and voltage. Results Patients with AF demonstrated the following compared with reference patients: larger atrial volumes (RA: 94 ± 18 ml vs. 69 ± 9 ml, p = 0.003; LA: 99 ± 19 ml vs. 77 ± 17 ml, p = 0.006); longer ERP (at 600 ms: 255 ± 25 ms vs. 222 ± 16 ms, p Conclusions Patients with paroxysmal lone AF, remote from arrhythmia, demonstrate bi-atrial abnormalities characterized by structural change, conduction abnormalities, and sinus node dysfunction. These factors are likely contributors to the “second factor” that predisposes to the development and progression of AF.

Background Three-dimensional virtual anatomic navigation is increasingly used during mapping and ablation of complex arrhythmias. NavX Fusion software aims to mold the virtual anatomy to the patient's computed tomography (CT) image; however, the accuracy and clinical usefulness of this system have not been reported. Objective The purpose of this study was to assess the accuracy and describe the initial experience of CT image integration using NavX Fusion for atrial fibrillation ablation. Methods This study consisted of 55 consecutive patients undergoing atrial fibrillation ablation using NavX Fusion navigation. Left atrial NavX geometries were compared to a corresponding CT for geometric match. Geometric match, expressed as the difference in millimeters between CT and NavX geometry, was calculated for the original geometry (GEO-1), field scaled and primary fused geometry (GEO-2), and final secondary fused geometry (GEO-3). Navigational accuracy was assessed by moving the catheter to 10 discrete anatomic sites and determining the distance between the catheter tip and the closest GEO-2, GEO-3, and CT surface. Fusion integration time and procedural and fluoroscopic durations were recorded to assess clinical usefulness. Results GEO-1, GEO-2 and GEO-3 were associated with CT–GEO errors of 6.6±2.8 mm, 4.1±0.7 mm, 1.9±0.4 mm, respectively. Navigational accuracy was not significantly different for GEO-2, GEO-3, and CT at 3.4±1.6 mm to any surface. A significant ( P ≤.001) inverse curvilinear relationship was present between case number and the time required for image integration (r 2 = 0.35) and the fluoroscopic time normalized for procedural duration (r 2 = 0.18). Conclusion Image integration using the NavX Fusion software is highly accurate and is associated with a progressive reduction in fluoroscopic time relative to procedural duration.

Sites of complex fractionated atrial electrograms (CFAEs) and highest dominant frequency (DF) have been proposed as critical regions maintaining atrial fibrillation (AF). This study aimed to determine the minimum electrogram recording duration that accurately characterizes CFAE or DF sites for ablation without unduly lengthening the procedure.Fourteen patients with AF undergoing catheter ablation had high-density (498 +/- 174 points) biatrial mapping performed during AF before ablation. At each point, 8-second electrograms were recorded. CFAE characterization using the NavX software provided a representation of electrogram complexity (CFE-mean). CFE-mean for each point from 7-, 6-, 5-, 4-, 3-, 2-, and 1-second subsamples were compared with the index 8-second CFE-mean. Offline spectral analysis defined DF as the frequency with greatest power, and DF of subsamples were compared with index DF. Index 8-second electrogram CFE-mean was 114 +/- 20 ms for right atria and 102 +/- 17 ms for left atria (P = 0.01); DF was 5.7 +/- 0.8 Hz for right atria and 6.0 +/- 0.8 Hz for left atria (P = 0.02). Means from shorter electrograms were nonsignificantly decreased for CFE-mean and overestimated for DF (P0.001). Mean absolute differences between subsampled and index values ranged from 3.3 to 20.1 ms for CFE-mean and 0.11 to 1.18 Hz for DF. Subsampled electrograms deviating10% from index values ranged from 2.5 to 56% for CFE-mean and 3.5 to 41% for DF. Intraclass correlation coefficients ranged from 0.992 to 0.788 for CFE-mean and 0.897 to 0.233 for DF. Unacceptable differences from index values were found with CFE-mean and DF from electrograms5 seconds.Electrograms ofor=5-second duration are required to accurately characterize CFAE and DF sites for ablation.

Lauren Wilson, Anthony G. Brooks, Dennis H. Lau, Hany Dimitri, Gautam Sharma, Han S. Lim, Muayad Alasady, Glenn D. Young, Prashanthan Sanders

Background: Both ageing and hypertension are known risk factors for atrial fibrillation (AF) although the pathophysiological contribution or interaction of the individual factors remains poorly understood. Here we aim to delineate the arrhythmogenic atrial substrate in mature spontaneously hypertensive rats (SHR). Methods: SHR were studied at 12 and 15 months of age (n=8 per group) together with equal numbers of age-matched normotensive Wistar-Kyoto control rats (WKY). Electrophysiologic study was performed on superfused isolated right and left atrial preparations using a custom built high-density multiple-electrode array to determine effective refractory periods (ERP), atrial conduction and atrial arrhythmia inducibility. Tissue specimens were harvested for structural analysis. Results: Compared to WKY controls, the SHR demonstrated: Higher systolic blood pressure (p

The aim of this study was to quantify cardiorespiratory interaction in patients with obstructive sleep apnea syndrome (OSAS) during night-time sleep using our recently proposed technique based on joint symbolic dynamics (JSD) and compare it with the synchrogram technique. We investigated overnight polysomnography data of 213 patients with OSAS. The R-R time series were extracted from electrocardiograms (ECG) and respiratory phases were obtained from abdominal displacement sensors using the Hilbert transform. For the JSD technique, both series were transformed into ternary symbol vectors based on the changes between two successive R-R intervals and the respective respiratory phases. Subsequently, words of length ‘3’ were formed and the correspondence between words of the two series was determined for each sleep stage to quantify cardio-respiratory interaction. To determine the effect of OSAS severity on cardiorespiratory interaction, the cohort was trichotomized based on the apnea-hypopnea index (AHI): AHI≤15, 15

Cardiac and respiratory rhythms reveal transient phases of phase-locking which were proposed to be an important aspect of cardiorespiratory interaction. The aim of this study was to quantify cardio-respiratory phase-locking in obstructive sleep apnea (OSA). We investigated overnight polysomnography data of 248 subjects with suspected OSA. Cardiorespiratory phase-coupling was computed from the R-R intervals of body surface ECG and respiratory rate, calculated from abdominal and thoracic sensors, using Hilbert transform. A significant reduction in phase-coupling was observed in patients with severe OSA compared to patients with no or mild OSA. Cardiorespiratory phase-coupling was also associated with sleep stages and was significantly reduced during rapid-eye-movement (REM) sleep compared to slow-wave (SW) sleep. There was, however, no effect of age and BMI on phase coupling. Our study suggests that the assessment of cardiorespiratory phase coupling may be used as an ECG based screening tool for determining the severity of OSA.

Atrial electrical remodeling has been shown after termination of atrial flutter (AFL); however, whether abnormalities persist beyond an arrhythmic episode is not known. We aimed to characterize the atrial substrate, remote from arrhythmia, in patients with typical AFL. We compared 20 patients, studied remote from episodes of typical AFL and without a history of atrial fibrillation, to 20 reference patients. Multipolar catheters placed at the lateral right atrium (RA), coronary sinus, crista terminalis, and septal RA measured the effective refractory period at 5 sites; conduction characteristics at the crista terminalis; and the conduction time along the lateral RA and coronary sinus. Electroanatomic right atrial maps were created to determine regional differences in voltage and conduction. Patients with AFL demonstrated the following compared to the reference patients: a larger right atrial volume (121 +/- 30 vs 83 +/- 24 ml, p = 0.005); a prolonged P-wave duration (122 +/- 18 vs 102 +/- 11 ms, p = 0.007); a longer right atrial activation time (107 +/- 23 vs 85 +/- 14 ms, p = 0.02); a prolonged conduction time along the lateral RA (67 +/- 4 vs 47 +/- 3 ms, p

Introduction: Measuring the postpacing interval (PPI) and correcting for the tachycardia cycle length (TCL) is an important entrainment response (ER). However, it may be impossible to measure PPI due to electrical noise on the mapping catheter. To overcome this problem, 2 alternative methods for the assessment of ER have been proposed: N+1 difference (N+1 DIFF) and PPIR method. PPI-TCL difference (PPI − TCL) correlates very well with ER assessed by new methods, but the agreement with PPI − TCL was established only in relation to PPIR method. Moreover, it is not known which of these methods is superior in the assessment of ER. Methods: We analyzed 155 episodes of ER in 21 patients with heterogeneous reentrant arrhythmias. ER was estimated by PPI − TCL and by both alternative methods. Agreement between methods was assessed by means of the Bland-Altman test, kappa coefficient (κ), and correlation coefficient (r). Finally, a mathematical comparison of the alternative methods was performed. Results: The agreement between PPI − TCL and alternative methods was very good. For N+1 DIFF the mean difference was −1.86 ± 7.31 ms; kappa = 0.9; r = 0.98; for PPIR method the mean difference was −1.46 ± 7.65 ms; kapa = 0.92; r = 0.99. Agreement between both alternative methods was also very high: the mean difference of 0.5 ± 6.6 ms; kappa = 0.89; r = 0.99. The analysis of the equations used for calculation of ER by these methods revealed that essentially they were mathematically equivalent. Conclusion: Each of the alternative methods may be used for evaluation of ER when PPI − TCL cannot be assessed directly. Results obtained by both alternative methods are comparable.

The purpose of this study was to determine whether patients with paroxysmal "lone" atrial fibrillation (AF) have an abnormal atrial substrate.While "AF begets AF," prompt termination to prevent electrical remodeling does not prevent disease progression.Twenty-five patients with paroxysmal lone AF, without arrhythmia in the week prior, and 25 reference patients with left-sided accessory pathways were studied. Multipolar catheters placed at the lateral right atrium (RA), crista terminalis, coronary sinus, septal RA, and sequentially within the left atrium (LA) determined the effective refractory period (ERP) at 10 sites, conduction time along linear catheters, and conduction characteristics at the crista terminalis. Bi-atrial electroanatomic maps were created to determine regional differences in conduction velocity and voltage.Patients with AF demonstrated the following compared with reference patients: larger atrial volumes (RA: 94 +/- 18 ml vs. 69 +/- 9 ml, p = 0.003; LA: 99 +/- 19 ml vs. 77 +/- 17 ml, p = 0.006); longer ERP (at 600 ms: 255 +/- 25 ms vs. 222 +/- 16 ms, p0.001; at 450 ms: 234 +/- 20 ms vs. 212 +/- 14 ms, p = 0.004); longer conduction time along linear catheters (57 +/- 18 ms vs. 47 +/- 10 ms, p = 0.01); longer bi-atrial activation time (128 +/- 17 ms vs. 89 +/- 10 ms, p0.001); slower conduction velocity (RA: 1.3 +/- 0.3 mm/ms vs. 2.1 +/- 0.5 mm/ms; LA: 1.2 +/- 0.2 mm/ms vs. 2.2 +/- 0.4 mm/ms, p0.001); greater proportion of fractionated electrograms (27 +/- 8% vs. 8 +/- 5%, p0.001); longer corrected sinus node recovery time (265 +/- 57 ms vs. 185 +/- 60 ms, p = 0.002); and lower voltage (RA: 1.7 +/- 0.4 mV vs. 2.9 +/- 0.4 mV; LA: 1.7 +/- 0.7 mV vs. 3.3 +/- 0.7 mV, p0.001).Patients with paroxysmal lone AF, remote from arrhythmia, demonstrate bi-atrial abnormalities characterized by structural change, conduction abnormalities, and sinus node dysfunction. These factors are likely contributors to the "second factor" that predisposes to the development and progression of AF.

Catheter ablation has rapidly gained acceptance as a mainstay of therapy for many symptomatic patients with atrial fibrillation since the original publication by the Bordeaux group [1]. Early on it became apparent that in most patients with par-oxysmal AF, the arrhythmia was initiated by focal firing in the pulmonary veins. Ablation focused on elimination of such triggers and was largely lim-ited to patients who would stay in sinus rhythm long enough to allow successful mapping within the pulmonary veins. As this was time consuming and was associated with high risk of developing pulmonary vein stenosis, ablation lesions were moved further and further away from the sources of focal firing with co-development of Circumfer-ential Pulmonary Vein Ablation (CPVA) [2] aim-ing to encompass pulmonary vein ostia with cir-cular lesions without verification of conduction block and Segmental Pulmonary Vein Isolation [3] evolving into Pulmonary Vein Antrum Isola-tion [4] with the targeted area similar to that in CPVA but with requisite documentation of entry and / or exit block of conduction. While successful in the majority of patients with paroxysmal AF, these approaches were lacking in patients with persistent and permanent AF. A concurrent ap-proach addressing the fibrillatory substrate was developed and proved to be a successful stand-alone alternative to lesions encircling the pulmo-nary veins at one center [5]. This approach had the advantage of better tailoring the lesion set to the individual patient and potentially limiting energy delivery and associated risks. Addressing fibrillatory conduction as an adjunct to ablating triggers had since become incorporated into the lesion set targeting persistent and permanent atri-al fibrillation in a stepwise approach popularized by the Bordeaux group [6]. At the same time better tools have enabled clinicians to probe deeper into the complex interaction of the mechanisms initi-ating and maintaining atrial fibrillation. So in ex-perimental models of atrial fibrillation “drivers” or areas of microreentry were seen surrounded by areas of fibrillatory conduction [7-9]. Research has pointed to the possibility of the “drivers” or “triggers” to be in close proximity to areas of atrial myocardium innervated by autonomic gan-glionated plexi with areas of fibrillatory conduc-tion 1-2 cm remote from these [10]. Relationship between areas of high dominant frequency and atrial tachyarrhythmias that follow AF ablation has been demonstrated [11] suggesting that such arrhythmias may actually drive AF prior to de-fragmentation.In their paper published last month [12], Drs Stiles and Brooks describe high-density bi-atrial map-ping during atrial fibrillation prior to ablation to identify areas of presumed drivers and fibrillato-ry conduction. The investigators collected around 500 points in each of the 20 patients during atrial fibrillation using a PentaRay (Biosense Webster, Diamond Bar, CA, USA) catheter and NavX soft-ware (St. Jude Medical, St. Paul, MN, USA). Each point was screened manually to eliminate points with unacceptable signal-to-noise ratio. Eight

The number of patients with implantable cardioverter–defibrillator (ICD) is rapidly increasing due to their expanding indications. Amongst the various types of electromagnetic interferences, little is reported about the effects of radiotherapy. We report a case of electrical reset of a single chamber ICD by scattered irradiation from radiotherapy.

We present a 51-year-old morbidly obese man who underwent insertion of a single-chamber implantable cardioverter defibrillator for monomorphic ventricular tachycardia occurring after myocardial infarction. After a period of satisfactory device function, a sudden change in R-wave with atrial over-sensing heralded inappropriate defibrillation and induction of ventricular fibrillation, with subsequent death of the patient.

obstruction (as determined by simultaneous polysomnography). Results: 20 obstructive episodes met the inclusion criteria. Mean O2 at the beginning (B) of the events was 95± 2.6%, nadir (N) 86± 4.1% and recovery (R) 95± 2.3%. ERP changes were dynamic but not different at the 3 time points (p= 0.07). CT across the CS was not different for S1, however, was significantly different for S2 (134± 30ms(B) vs. 148± 26ms(N) vs. 147± 40ms(R); p= 0.01). Lateral CT significantly changed for S1 (119± 20ms(B) vs. 126± 18ms(N) vs. 123± 20ms(R)) and S2 (177± 44ms(B) vs. 207± 38ms(N) vs. 207± 48ms(R); p= 0.03) measures. Local conduction delay (CD=A1A2−S1S2)was significantly different at the distal CS (63± 20ms(B) vs. 70± 15ms(N) vs. 74± 24ms(R); p= 0.01) and lateral RA (78± 26ms(B) vs. 97± 21ms(N) vs. 92± 30ms(R); p< 0.001). Conclusion: Acute obstruction during sleep apnoea results in significant atrial remodelling characterized by slowing of conduction during obstruction and incomplete recovery after the event. These changes may account in part for the development of AF in association with clinical OSA. doi:10.1016/j.hlc.2010.06.921

Background: Incessant focal atrial tachycardia (AT)may be complicated by LV dysfunction. The aim was to characterise the incidence, ECG and EP features of incessant focal AT and identify predictors of tachycardia mediated cardiomyopathy (TCM). Methods: 82 of 345 (24%) pts with focal AT presenting for radiofrequency ablation between 1997 and 2008 were incessant. Incessant AT was defined as continuous tachycardia or recurrent paroxysms of tachycardia separated by ≤2 sinus beats. Results: The mean age was 42± 20 years, 57% were male and mean symptom duration was 5± 7 years. TCM was present in 30/82 (37%), defined as LVEF

mode. These findings indicate persistent native heart offloading even with intermittent compression. doi:10.1016/j.hlc.2009.05.170