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Obstructive sleep apnea (OSA) importantly contributes to the occurrence of atrial fibrillation (AF) in humans, but the mechanisms are poorly understood. Experimental research has provided insights into AF promotion by acute OSA episodes. However, patients with OSA usually have frequent nocturnal episodes for some time before manifesting AF.The goal of this study was to test the hypothesis that repetitive OSA causes cardiac remodeling that predisposes to AF.We mimicked OSA by using a mechanical ventilator and closing the airway at end-expiration with a 3-way stopcock (OSA rats). Matched control groups included rats with the ventilator stopped but airway left open (open airway rats) and continuously ventilated rats (sham rats). OSA rats were exposed to 20 consecutive 2-min cycles of 40 s of apnea/80 s of ventilation per day, 5 days per week for 4 weeks.OSA significantly increased the duration of AF from (median [interquartile range]) 2.6 s [1.9 s to 8.9 s] (shams) and 16 s [1.8 s to 93 s] (open airway) to 49s [34 s to 444 s]. AF inducibility increased to 56% (9 of 16) of OSA rats; this is up from 15% (2 of 13) and 13% (2 of 15) in open airway and sham rats, respectively (p 0.05). OSA rats exhibited substantial atrial conduction slowing on optical mapping, along with connexin-43 down-regulation on both quantitative immunofluorescence (expression reduced by 58% vs sham rats) and Western blot (reduced by 38%), as well as increased atrial fibrous tissue content (by 71%). OSA also caused left ventricular hypertrophy, dilation, and diastolic dysfunction and enhanced AF inducibility during superimposed acute OSA episodes to 82.4% of rats.Chronically repeated OSA episodes cause AF-promoting cardiac remodeling, with conduction abnormalities related to connexin dysregulation and fibrosis playing a prominent role. This novel animal model provides mechanistic insights into an important clinical problem and may be useful for further exploration of underlying mechanisms and therapeutic approaches.

Objectives The aim of this study was to determine if ablation that targets patient-specific atrial fibrillation (AF)-sustaining substrates (rotors or focal sources) is more durable than trigger ablation alone at preventing late AF recurrence. Background Late recurrence substantially limits the efficacy of pulmonary vein isolation for AF and is associated with pulmonary vein reconnection and the emergence of new triggers. Methods Three-year follow-up was performed of the CONFIRM (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation) trial, in which 92 consecutive patients with AF (70.7% persistent) underwent novel computational mapping. Ablation comprised source (focal impulse and rotor modulation [FIRM]) and then conventional ablation in 27 patients (FIRM guided) and conventional ablation alone in 65 patients (FIRM blinded). Patients were followed with implanted electrocardiographic monitors when possible (85.2% of FIRM-guided patients, 23.1% of FIRM-blinded patients). Results FIRM mapping revealed a median of 2 (interquartile range: 1 to 2) rotors or focal sources in 97.7% of patients during AF. During a median follow-up period of 890 days (interquartile range: 224 to 1,563 days), compared to FIRM-blinded therapy, patients receiving FIRM-guided ablation maintained higher freedom from AF after 1.2 ± 0.4 procedures (median 1; interquartile range: 1 to 1) (77.8% vs. 38.5%, p = 0.001) and a single procedure (p < 0.001) and higher freedom from all atrial arrhythmias (p = 0.003). Freedom from AF was higher when ablation directly or coincidentally passed through sources than when it missed sources (p < 0.001). Conclusions FIRM-guided ablation is more durable than conventional trigger-based ablation in preventing 3-year AF recurrence. Future studies should investigate how ablation of patient-specific AF-sustaining rotors and focal sources alters the natural history of arrhythmia recurrence. (The Dynamics of Human Atrial Fibrillation; NCT01008722). © 2014 by the American College of Cardiology Foundation. Published by Elsevier Inc.

The historical origin of the term "lone atrial fibrillation" (AF) predates by 60 years our current understanding of the pathophysiology of AF, the multitude of known etiologies for AF, and our ability to image and diagnose heart disease. The term was meant to indicate AF in patients for whom subsequent investigations could not demonstrate heart disease, but for many practitioners has become synonymous with "idiopathic AF." As the list of heart diseases has expanded and diagnostic techniques have improved, the prevalence of lone AF has fallen. The legacy of the intervening years is that definitions of lone AF in the literature are inconsistent so that studies of lone AF are not comparable. Guidelines provide a vague definition of lone AF but do not provide direction about how much or what kind of imaging and other testing are necessary to exclude heart disease. There has been an explosion in the understanding of the pathophysiology of AF in the last 20 years in particular. Nevertheless, there are no apparently unique mechanisms for AF in patients categorized as having lone AF. In addition, the term "lone AF" is not invariably useful in making treatment decisions, and other tools for doing so have been more thoroughly and carefully validated. It is, therefore, recommended that use of the term "lone AF" be avoided.

Ablation for atrial fibrillation (AF) is an important and exciting therapy whose results remain suboptimal. Although most clinical trials show that ablation eliminates AF more effectively than medications, it is disappointing that the continued single procedural success remains ≈50% despite the substantial advances that have taken place in imaging, catheter positioning and energy delivery. Focal impulse and rotor modulation (FIRM), on the other hand, offers the opportunity to precisely define and then ablate patient-specific sustaining mechanisms for AF, rather than trying to eliminate all possible AF triggers. For over a decade, electrophysiologists have described cases in which AF terminates after only limited ablation – usually that cannot be explained by ‘random’ meandering wavelets. Indeed, recent studies from several laboratories show that all forms of clinical AF are typically ‘driven’ by stable electrical rotors and focal sources, not by multiple meandering waves. FIRM mapping enables an operator to place a catheter at typically 1-3 predicted sites in the atria, and with 80% of patients with persistent and paroxysmal AF and increase the single procedure rate of AF elimination from 50% with PV isolation alone to >80%. Ongoing studies hint that FIRM only ablation, enabling ablation times in the range observed for typical atrial flutter, may also achieve these high success rates without subsequent trigger ablation. This review summarizes the current state-of-the-art on FIRM mapping and ablation.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is a major cause of strokes, hospitalizations, and mortality in the United States. The toll of AF is expected to worsen in coming decades as the number of elderly Americans increases (1). This harsh demographic reality has provided an impetus to seek new strategies to prevent, control, and eliminate the arrhythmia. About a decade ago, it was discovered that AF is frequently triggered by ectopy or bursts of tachycardia that originate in muscle bundles that extend from the atrium to the pulmonary veins (PVs) (2) and that electrical pulmonary vein isolation (PVI) by transcatheter ablation can maintain sinus rhythm. The past decade has witnessed great enthusiasm for PVI. With current techniques, 50% to 60% of patients remain in sinus rhythm 1 year after a single procedure (3), but the remainder show early or late recurrence of AF (4).

ObjectivesThe aim of this study was to determine whether onset sites of human atrial fibrillation (AF) exhibit conduction slowing, reduced amplitude, and/or prolonged duration of signals (i.e., fractionation) immediately before AF onset.BackgroundFew studies have identified functional determinants of AF initiation. Because conduction slowing is required for reentry, we hypothesized that AF from pulmonary vein triggers might initiate at sites exhibiting rate-dependent slowing in conduction velocity (CV restitution) or local slowing evidenced by signal fractionation.MethodsIn 28 patients with AF (left atrial size 43 ± 5 mm; n = 13 persistent) and 3 control subjects (no AF) at electrophysiological study, we measured bi-atrial conduction time (CT) electrogram fractionation at 64 or 128 electrodes with baskets in left (n = 17) or both (n = 14) atria during superior pulmonary vein pacing at cycle lengths (CL) accelerating from 500 ms (120 beats/min) to AF onset.ResultsAtrial fibrillation initiated in 19 of 28 AF patients and no control subjects. During rate acceleration, conduction slowed in 23 of 28 AF patients (vs. no control subjects, p = 0.01) at the site of AF initiation (15 of 19) or latest activated site (20 of 28). The CT lengthened from 79 ± 23 ms to 107 ± 39 ms (p < 0.001) on acceleration, in a spectrum from persistent AF (greatest slowing) to control subjects (least slowing; p < 0.05). Three patterns of CV restitution were observed: 1) broad (gradual CT prolongation, 37% patients); 2) steep (abrupt prolongation, at CL 266 ± 62 ms, 42%); and 3) flat (no prolongation, 21% AF patients, all control subjects). The AF initiation was more prevalent in patients with CV restitution (17 of 23 vs. 2 of 8; p = 0.03) and immediately followed abrupt re-orientation of the activation vector in patients with broad but not steep CV restitution (p < 0.01). Patients with broad CV restitution had larger atria (p = 0.03) and were more likely to have persistent AF (p = 0.04). Notably, neither amplitude nor duration (fractionation) of the atrial signal at the AF initiation site were rate-dependent (both p = NS).ConclusionsAcceleration-dependent slowing of atrial conduction (CV restitution) precedes AF initiation, whereas absence of CV restitution identifies inability to induce AF. Conduction restitution, but not fractionated electrograms, may thus track the functional milieu enabling AF initiation and has implications for guiding AF ablation and pharmacological therapy.

Termination of persistent atrial fibrillation (AF) is a valuable ablation endpoint but is difficult to anticipate. We evaluated whether temporal and spatial indices of AF regularization predict intraprocedural AF termination and outcome.The purpose of this study was to test whether temporospatial organization of AF after pulmonary vein isolation (PVI) predicts whether subsequent stepwise ablation will terminate persistent AF or predict outcome.In 75 patients with persistent AF, we measured AF cycle length (AFCL), temporal regularity index (TRI, a spectral measure of timing regularity), and spatial regularity index (SRI, cycle-to-cycle variations in spatial vector) between right atrial appendage and proximal and distal coronary sinus before and during stepwise ablation to the endpoint of AF termination.AF termination was achieved in 59 patients (79%) by ablation. AF terminated during PVI in 11 patients, who were excluded from analysis. In the remaining 48 patients, TRI and SRI increased during stepwise ablation, as compared with 16 patients without termination (P.05). AFCL was prolonged in both groups. From receiver operating characteristics analysis of the first 22 patients (training set), a post-PVI TRI increase predicted AF termination in the latter 42 patients (test set) with a positive predictive value of 96%, negative predictive value of 53%, sensitivity of 71%, and specificity of 91%. Results were similar for SRI. After 36 months, higher arrhythmia-free outcome was observed in patients in whom PVI caused temporospatial regularization in AF.Temporal and spatial regularization of persistent AF after PVI identifies patients in whom stepwise ablation subsequently terminates AF and prevents recurrence.

ObjectivesThis multicenter study sought to evaluate the long-term follow-up of patients ablated for idiopathic ventricular fibrillation (VF).BackgroundCatheter ablation of idiopathic VF that targets ventricular premature beat (VPB) triggers has been shown to prevent VF recurrences on short-term follow-up.MethodsFrom January 2000, 38 consecutive patients from 6 different centers underwent ablation of primary idiopathic VF initiated by short coupled VPB. All patients had experienced at least 1 documented VF, with 87% having experienced ≥2 VF episodes in the preceding year. Catheter ablation was guided by activation mapping of VPBs or pace mapping during sinus rhythm.ResultsThere were 38 patients (21 men) age 42 ± 13 years, refractory to a median of 2 antiarrhythmic drugs. Triggering VPBs originated from the right (n = 16), the left (n = 14), or both (n = 3) Purkinje systems and from the myocardium (n = 5). During a median post-procedural follow-up of 63 months, 7 (18%) of 38 patients experienced VF recurrence at a median of 4 months. Five of these 7 patients underwent repeat ablation without VF recurrence. Survival free of VF was predicted only by transient bundle-branch block in the originating ventricle during the electrophysiological study (p < 0.0001). The number of significant events (confirmed VF or aborted sudden death) was reduced from 4 (interquartile range 3 to 9) before to 0 (interquartile range 0 to 4) after ablation (p = 0.01).ConclusionsAblation for idiopathic VF that targets short coupled VPB triggers is associated with a long-term freedom from VF recurrence.

The authors sought to study mechanisms to explain why single premature atrial complexes (PACs) from the pulmonary veins (PVs) may initiate human atrial fibrillation (AF).Theoretically, single PACs may initiate AF if the rate response of action potential duration (APD) restitution has a slope1. However, human left atrial APD restitution and its relationship to AF have not been studied. We hypothesized that an APD restitution slope1 near PVs explains the initiation of clinical AF.We studied 27 patients with paroxysmal and persistent (n = 13) AF. We advanced monophasic action potential catheters transseptally to superior PVs. Restitution was plotted as APD of progressively early PACs against their diastolic interval (DI) from prior beats. Activation time restitution was measured using the time from the pacing artifact to each PAC.Compared with paroxysmal AF, patients with persistent AF had shorter left atrial APD and effective refractory period (p = 0.01). In paroxysmal AF, maximum left atrial APD restitution slope was 1.5 +/- 0.4; and 12 of 13 patients had slope1 (p0.001). In persistent AF, PACs encountered prolonged activation for a wider range of beats than in paroxysmal AF (p = 0.01), which prolonged DI and flattened APD restitution (slope 0.7 +/- 0.2; p0.001); no patient had APD restitution slope1. A single PAC produced AF in 5 patients; in all, an APD restitution slope1 caused extreme APD oscillations after the PAC, then AF.In patients with paroxysmal AF, maximum APD restitution slope1 near the PVs enables single PACs to initiate AF. However, patients with persistent AF show marked dynamic activation delay near PVs that flattens APD restitution. Studies should determine how regional APD and conduction dynamics contribute to the substrates of persistent AF.