Rationale: Sleep-disordered breathing recurrent intermittent hypoxia and sympathetic nervous system activity surges provide the milieu for cardiac arrhythmia development. Objective: We postulate that the prevalence of nocturnal cardiac arrhythmias is higher among subjects with than without sleepdisordered breathing. Methods: The prevalence of arrhythmias was compared in two samples of participants from the Sleep Heart Health Study frequencymatched on age, sex, race/ethnicity, and body mass index: (1 ) 228 subjects with sleep-disordered breathing (respiratory disturbance index у 30) and (2 ) 338 subjects without sleep-disordered breathing (respiratory disturbance index Ͻ 5). Supported by National Heart, Lung and Blood Institute cooperative agreements U01HL53940 (University of Washington), U01HL53941 (Boston University), U01HL53938 (University of Arizona), U01HL53916 (University of California, Davis), U01HL53934 (University of Minnesota), U01HL53931 (New York University), U01HL53937 and U01HL64360 (Johns Hopkins University), U01HL63463 (Case Western Reserve University), and U01HL63429 (Missouri Breaks Research).The opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the Indian Health Service.Correspondence and requests for reprints should be addressed to Reena Mehra, M.D., M.S., Case Western Reserve University, University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, OH 44106. E-mail: mehrar@ameritech.net This article has an online supplement, which is accessible from this issue's table of contents at www.atsjournals.org Patients with sleep-disordered breathing (SDB) may be predisposed to arrhythmias because of alterations in sympathetic and parasympathetic nervous system activity occurring with SDBassociated hypoxemia, acidosis, apneas, and arousal (1-3). Mechanisms of arrhythmogenesis involve abnormal automaticity, triggered automaticity, and reentry mechanisms. Abnormal automaticity involves spontaneous cardiac impulse formation and may occur in SDB due to hypoxemia and respiratory acidosis accompanying apneic events (4). Triggered automaticity, pacemaker activity due to a stimulated action potential, may arise in SDB due to enhanced sympathetic nervous system activity associated with respiratory event-related hypoxemia and arousal (5). Reentry mechanisms may occur through the vagal stimulation that results from respiration against a partially occluded airway, which may lead to bradycardia-dependent increased dispersion of atrial repolarization predisposing to intraatrial entry (5-7). Also, SDB-related mechanical effects of negative intrathoracic pressure on the atrial and ventricular free walls promote cardiac stretch, which may predispose to arrhythmias via mechanicalelectrical feedback mechanisms (8).Despite the biological plausibility for SDB-associated hypoxemia, arousals, and autonomic nervous system dysregulation causing generation of abnormal cardiac electrophysiologic impulses, only limited research has rigorously characterized the association...

Background-The mechanisms of chronic atrial fibrillation (AF) are not well understood. We performed epicardial mapping of chronic AF in patients undergoing open heart surgery to test the hypothesis that chronic AF is due to a left atrial "driver" with a regular, short cycle length, resulting in fibrillatory conduction to the rest of the atria. Methods and Results-Nine patients with chronic AF (1 month to Ͼ15 years' duration) were studied at open heart surgery, 8 before and 1 during cardiopulmonary bypass. During AF, atrial electrograms (AEGs) were recorded for 1 to 5 minutes from 404 epicardial electrodes arranged in bipoles along with ECG lead II or ventricular electrogram. Four-second segments of each bipolar AEG were also subjected to fast Fourier transform analysis. Two patterns of atrial activation were present during AF. In pattern 1 (7/9 patients), AEGs from parts of the atria demonstrated a short, regular cycle length with identical beat-to-beat morphology, and the rest of the atria were activated irregularly, and AEGs that demonstrated constant morphology and cycle length were localized to parts of the left atria (5/7), the right atria (1/7), or both atria (1/7). In pattern 2 (2/9 patients), AEGs showed no evidence of regular activation or constant morphology. Conclusions-In 9 patients with chronic AF, the commonest recorded AEG pattern showed an area of regular, rapid rhythm, consistent with the possibility that a driver causing fibrillatory conduction is one mechanism of AF in these patients.

Background The mechanism(s) of persistent and long-standing persistent (LSP) atrial fibrillation (AF) is/are poorly understood. We performed high density, simultaneous, bi-atrial, epicardial mapping of persistent and LSP AF in patients undergoing open heart surgery (OHS) 1) to test the hypothesis that persistent and LSP AF are due to one or more drivers, either focal or reentrant, and 2) to characterize associated atrial activation. Methods and Results Twelve patients with persistent and LSP AF (1 month - 9 years duration) were studied at OHS. During AF, electrograms (AEGs) were recorded from both atria simultaneously for 1-5 minutes from 510-512 epicardial electrodes with ECG lead II. Thirty-two consecutive seconds of activation sequence maps were produced per patient. During AF, multiple foci (QS unipolar AEGs) of different cycle lengths (mean 175±18 ms) were present in both atria in 11/12 patients. Foci (2-4 per patient, duration 5-32 secs) were either sustained or intermittent, were predominantly found in the lateral left atrial free wall, and likely acted as drivers. Random and nonrandom breakthrough activation sites (initial r or R in unipolar AEGs) were also found. In 1/12 patients, only breakthrough sites were found. All wave fronts emanated from foci and/or breakthrough sites, and largely either collided or merged with each other at variable sites. Repetitive focal QS activation occasionally generated repetitive wannabe reentrant activation in 5/12 patients. No actual reentry was found. Conclusions During persistent and LSP AF in 12 patients, wave fronts emanating from foci and/or breakthrough sites maintained AF. No reentry was demonstrated.

In this CHF model, FFT analysis and activation sequence mapping demonstrate that sustained AF is characterized by single and multiple, stable LA and RA drivers with predominant sources in the PVs and high RA causing fibrillatory conduction.

This prospective multicenter series shows a high success rate of ECM in accurately diagnosing the mechanism of AT and the location of focal arrhythmia. Intraprocedural use of the system and its application to atrial fibrillation mapping is under way.

The canine sterile pericarditis model is characterized by impaired conduction and atrial arrhythmia vulnerability. Electrical and structural remodeling processes caused by the inflammatory response likely promote these abnormalities. In the present study, we tested the hypothesis that altered distribution of atrial connexins is associated with markedly abnormal atrial conduction, thereby contributing to vulnerability to atrial flutter (AFL) and atrial fibrillation (AF) induction and maintenance. During rapid pacing and induced, sustained AFL or AF in five sterile pericarditis (SP) and five normal (NL) dogs, epicardial atrial electrograms were recorded simultaneously from both atria (380 electrodes) or from the right atrium (RA) and Bachmann's bundle (212 electrodes). Tissues from RA sites were subjected to immunostaining and immunoblotting to assess connexin (Cx) 40 and Cx43 distribution and expression. Transmural myocyte (alpha-actinin) and fibroblast (vimentin) volume were also assessed by immunostaining. RA pacing maps showed markedly abnormal conduction in SP, with uniform conduction in NL. Total RA activation time was significantly prolonged in SP vs. NL at 300-ms and 200-ms pacing-cycle lengths. Sustained arrhythmias were only inducible in SP [total: 4/5 (AFL: 3/5; AF: 1/5)]. In NL, Cx40, Cx43, alpha-actinin, and vimentin were homogeneously distributed transmurally. In SP, Cx40, Cx43, and alpha-actinin were absent epicardially, decreased midmyocardially, and normal endocardially. SP increased epicardial vimentin expression, suggesting fibroblast proliferation. Immunoblot analysis confirmed reduced expression of Cx40 and Cx43 in SP. The transmural gradient in the volume fraction of Cx40 and Cx43 in SP is associated with markedly abnormal atrial conduction and is likely an important factor in the vulnerability to induction and maintenance of AFL/AF in SP.

Background— Twelve lead ECGs have limited value in precisely identifying atrial and ventricular activation during arrhythmias, including accessory atrioventricular conduction activation. The aim of this study was to report a single center’s clinical experience validating a novel, noninvasive, whole heart, beat-by-beat, 3-dimensional mapping technology with invasive electrophysiological studies, including ablation, where applicable. Methods and Results— Using an electrocardiographic mapping (ECM) system in 27 patients, 3-dimensional epicardial activation maps were generated from >250 body surface ECGs using heart–torso geometry obtained from computed tomographic images. ECM activation maps were compared with clinical diagnoses, and confirmed with standard invasive electrophysiological studies mapping. (1) In 6 cases of Wolff–Parkinson–White syndrome, ECM accurately identified the ventricular insertion site of an accessory atrioventricular connection. (2) In 10 patients with premature ventricular complexes, ECM accurately identified their ventricular site of origin in 8 patients. In 2 of 10 patients transient premature ventricular complex suppression was observed during ablation at the site predicted by ECM as the earliest. (3) In 10 cases of atrial tachycardia/atrial flutter, ECM accurately identified the chamber of origin in all 10, and distinguished isthmus from nonisthmus dependent atrial flutter. (4) In 1 patient with sustained exercise induced ventricular tachycardia, ECM accurately identified the focal origin in the left ventricular outflow tract. Conclusions— ECM successfully provided valid activation sequence maps obtained noninvasively in a variety of rhythm disorders that correlated well with invasive electrophysiological studies.

Manifest NFV pathways presented with variable QRS expression dependent on the ventricular insertion site and often coexisted with other tachycardia mechanisms (atrioventricular nodal reentry tachycardia and atrioventricular reentrant tachycardia). In most cases, the atrial insertion of the pathway was in or near the slow pathway region. The NFV pathways were either critical to the tachycardia circuit or served as bystanders.