Hany Dimitri

Atrial remodeling in obstructive sleep apnea: implications for atrial fibrillation.

BACKGROUND 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. OBJECTIVE To determine whether patients with OSA have an abnormal atrial substrate. METHODS 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 index < 15] 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). RESULTS 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). CONCLUSION 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.

High-Density Mapping of Atrial Fibrillation in Humans: Relationship Between High-Frequency Activation and Electrogram Fractionation

Introduction: Sites of complex fractionated atrial electrograms (CFAE) and dominant frequency (DF) have been implicated in maintaining atrial fibrillation (AF); however, their relationship is poorly understood.

The Effect of Electrogram Duration on Quantification of Complex Fractionated Atrial Electrograms and Dominant Frequency

Introduction: 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.

Image integration using NavX fusion: Initial experience and validation

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 patients 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 < or =.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.

Atrial Arrhythmia in Ageing Spontaneously Hypertensive Rats: Unraveling the Substrate in Hypertension and Ageing

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<0.0001), bi-atrial enlargement (p<0.05), bi-ventricular hypertrophy (p<0.05), lower atrial ERP (p = 0.008), increased atrial conduction heterogeneity (p = 0.001) and increased atrial interstitial fibrosis (p = 0.006) & CD68-positive macrophages infiltration (p<0.0001). These changes resulted in higher atrial arrhythmia inducibility (p = 0.01) and longer induced AF episodes (p = 0.02) in 15-month old SHR. Ageing contributed to incremental bi-atrial hypertrophy (p<0.01) and atrial conduction heterogeneity (p<0.01) without affecting atrial ERP, fibrosis and arrhythmia inducibility. The limited effect of ageing on the atrial substrate may be secondary to the reduction in CD68-positive macrophages. Conclusions Significant atrial electrical and structural remodeling is evident in the ageing spontaneously hypertensive rat atria. Concomitant hypertension appears to play a greater pathophysiological role than ageing despite their compounding effect on the atrial substrate. Inflammation is pathophysiologically linked to the pro-fibrotic changes in the hypertensive atria.

Cardiorespiratory Phase-Coupling Is Reduced in Patients with Obstructive Sleep Apnea

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.

Direction-dependent conduction in lone atrial fibrillation

BACKGROUND Patients with lone atrial fibrillation (AF) have an abnormal atrial substrate. OBJECTIVE The purpose of this study was to determine the role of direction-dependent conduction in patients with lone AF. METHODS 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. RESULTS 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. CONCLUSION 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.

Characterization of Atrial Remodeling Studied Remote from Episodes of Typical Atrial Flutter

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 <0.001); a slower mean conduction velocity (1.2 +/- 0.2 vs 2.1 +/- 0.6 mm/ms, p <0.001); a greater proportion of fractionated electrographic findings (16 +/- 4% vs 10 +/- 6%, p = 0.006); more frequent abnormal electrographic findings at the crista terminalis (4.1 +/- 2.6 vs 1.0 +/- 1.1, p = 0.001); a prolonged corrected sinus node recovery time (318 +/- 71 vs 203 +/- 94 ms, p = 0.02); a trend toward greater effective refractory period (232 +/- 29 vs 213 +/- 12 ms, p = 0.06); and a lower voltage (2.1 +/- 0.5 vs 3.0 +/- 0.5 mV, p <0.001). In conclusion, studied remote from arrhythmia, patients with AFL demonstrated significant and diffuse atrial abnormalities characterized by structural changes, conduction abnormalities, and sinus node dysfunction. These persisting abnormalities characterize the substrate underlying typical AFL and may account for the subsequent development of atrial fibrillation.

Clinical Validation and Comparison of Alternative Methods for Evaluation of Entrainment Mapping

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.

Feasibility of high-density electrophysiological study using multiple-electrode array in isolated small animal atria.

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).