Rapid Atrial Rates Research Articles

Incidence and Determinants of Spontaneous Cardioversion of Early Onset Symptomatic Atrial Fibrillation

Atrial fibrillation (AF) is the most frequent chronic arrhythmia worldwide, and it is associated with significant morbidity and mortality, making it a considerable burden both to patients and the healthcare system. Nowadays, an early attempt to restore sinus rhythm in acute symptomatic AF through electrical or pharmacological cardioversion is the most common approach in the Emergency Department (ED). However, considering the high percentage of spontaneous cardioversion of paroxysmal AF reported by many studies, this approach may not be the ideal choice for all patients. In this manuscript we performed a review of the most relevant studies found in literature with the aim of identifying the main determinants of spontaneous cardioversion, focusing on those easy to detect in the ED. We have found that the most relevant predictors of spontaneous cardioversion are the absence of Heart Failure (HF), a small atrial size, recent-onset AF, rapid Atrial Fibrillatory Rate and the relationship between a previous AF episode and Heart Rate/Blood Pressure. A number of those are utilized, along with other easily determined parameters, in the recently developed "ReSinus" score which predicts the likelihood of AF spontaneous cardioversion. Such identification may help the physician decide whether immediate cardioversion is necessary, or whether to adopt a "watch-and-wait" strategy in the presence of spontaneous cardioversion determinants.

The Role of Mitochondrial Dysfunction in Atrial Fibrillation: Translation to Druggable Target and Biomarker Discovery.

Atrial fibrillation (AF) is the most prevalent and progressive cardiac arrhythmia worldwide and is associated with serious complications such as heart failure and ischemic stroke. Current treatment modalities attenuate AF symptoms and are only moderately effective in halting the arrhythmia. Therefore, there is an urgent need to dissect molecular mechanisms that drive AF. As AF is characterized by a rapid atrial activation rate, which requires a high energy metabolism, a role of mitochondrial dysfunction in AF pathophysiology is plausible. It is well known that mitochondria play a central role in cardiomyocyte function, as they produce energy to support the mechanical and electrical function of the heart. Details on the molecular mechanisms underlying mitochondrial dysfunction are increasingly being uncovered as a contributing factor in the loss of cardiomyocyte function and AF. Considering the high prevalence of AF, investigating the role of mitochondrial impairment in AF may guide the path towards new therapeutic and diagnostic targets. In this review, the latest evidence on the role of mitochondria dysfunction in AF is presented. We highlight the key modulators of mitochondrial dysfunction that drive AF and discuss whether they represent potential targets for therapeutic interventions and diagnostics in clinical AF.

ASSOCIATION OF SUBCLINICAL ATRIAL FIBRILLATION WITH RISK OF STROKE: RESULTS FROM A META-ANALYSIS

In this meta-analysis we systemically evaluated the evidences regarding the association of subclinical events of rapid atrial rate episodes (AHRE) detected by implanted devices, with risk of stroke. Pubmed, Medline and other databases were searched for trials that reported relation between

806Implantable loop recorders and short episodes of rapid atrial rate: relevant in the medical work-up of patients with embolic strokes of unknown source

806Implantable loop recorders and short episodes of rapid atrial rate: relevant in the medical work-up of patients with embolic strokes of unknown source

Abstract 12665: Remodeling of Nuclear Ca 2+ Disposition in Atrial Fibrillation Associated Remodeling

Introduction: Atrial fibrillation (AF) induces substantial self-promoting remodeling related to the rapid atrial rate. There is evidence that changes in nuclear Ca 2+ content alter ion channel gene expression and thereby effect electrophysiological changes that increase AF vulnerability and maintenance. However, the ways in which AF affects atrial cardiomyocyte (ACM) nuclear Ca 2+ disposition are unknown. Here, we studied the effects of AF-related remodeling on ACM nuclear structure and Ca 2+ handling. Methods and Results: ACMs were isolated from control (CTL) dogs and dogs subjected to 1 week of AF maintained by atrial tachypacing at 600 bpm (n=7, 6 respectively). We used nuclear imaging with Fluo-5N AM and nucleoplasmic and cytoplasmic calcium transient (CaT) recordings from intact ACMs loaded with Fluo-4 AM. AF significantly decreased the number of nuclear invaginations (NIV) normalized to nuclear envelope (NE) circumference, and increased nuclear length and perimeter in ACMs (Figure A). Diastolic [Ca 2+ ] nuc and [Ca 2+ ] cyto increased in AF vs CTL (Figure B, by 110%*, 89%* respectively, *P<0.05). Nucleoplasmic Ca 2+ transient amplitude decreased significantly with AF, but simultaneously measured cytoplasmic transient amplitude did not change (Figure C). Relaxation time from peak of the Ca 2+ transient to 50% decline (TD 50 ) of nucleoplasmic and cytoplasmic CaTs were significantly prolonged in AF. The addition of a physiological nuclear Ca 2+ transient enhancer, endothelin (200 nM), increased diastolic [Ca 2+ ] nuc and [Ca 2+ ] cyto in both CTL (by 25±6%, 21±6%) and AF (by 40±4%, 31±2 ) ACMs. The IP3 receptor blocker 2-aminoethoxydiphenyl borate (2-APB, 5 μM) abolished endothelin effects on [Ca 2+ ] nuc . Conclusions: AF-related remodeling alters atrial cardiomyocyte nuclear structure and nucleoplasmic [Ca 2+ ] handling. These alterations may play an important role in associated gene-expression changes that produce the AF substrate.

Cardiac MRI assessment of atrial fibrosis in atrial fibrillation: implications for diagnosis and therapy

Atrial fibrillation (AF) is the most commonly encountered cardiac arrhythmia in clinical practice, with a prevalence of 0.4–1% in the US population.w1 AF is a potent risk factor, increasing the...

Effect of Atrial Fibrillation on Atrial Thrombogenesis in Humans: Impact of Rate and Rhythm

We sought to assess the effect of atrial fibrillation (AF) on atrial thrombogenesis in humans by determining the impact of rate and rhythm. Although AF is known to increase the risk of thromboembolic stroke from the left atrium (LA), the exact mechanisms remain poorly understood. We studied 55 patients with AF who underwent catheter ablation while in sinus rhythm; 20 patients were induced into AF, 20 patients were atrial paced at 150 beats/min, and 15 were control patients. Blood samples were taken from the LA, right atrium, and femoral vein at baseline and at 15 min in all 3 groups. Platelet activation (P-selectin) was measured by flow cytometry. Thrombin generation (thrombin-antithrombin [TAT] complex), endothelial dysfunction (asymmetric dimethylarginine [ADMA]), and platelet-derived inflammation (soluble CD40 ligand [sCD40L]) were measured using enzyme-linked immunosorbent assay. Platelet activation increased significantly in both the AF (p < 0.001) and pacing (p < 0.05) groups, but decreased in control patients (p < 0.001). Thrombin generation increased specifically in the LA compared with the periphery in both the AF (p < 0.01) and pacing (p < 0.01) groups, but decreased in control patients (p < 0.001). With AF, ADMA (p < 0.01) and sCD40L (p < 0.001) levels increased significantly at all sites, but were unchanged with pacing (ADMA, p = 0.5; sCD40L, p = 0.8) or in control patients (ADMA, p = 0.6; sCD40L, p = 0.9). Rapid atrial rates and AF in humans both result in increased platelet activation and thrombin generation. Prothrombotic activation occurs to a greater extent in the human LA compared with systemic circulation. AF additionally induces endothelial dysfunction and inflammation. These findings suggest that although rapid atrial rates increase the thrombogenic risk, AF may further potentiate this risk.

How early is early enough to prevent stroke in atrial fibrillation?

Evaluation of: Healey JS, Connolly SJ, Gold MR et al. Subclinical atrial fibrillation and the risk of stroke. N. Engl. J. Med. 366(2), 120–129 (2012).Atrial fibrillation (AF) is a potent risk factor for stroke, being responsible for 20% of ischemic strokes. Subclinical AF burden has received much attention, especially in the context of patients with cryptogenic strokes. However, little is known about the impact of subclinical episodes of rapid atrial rate and the primary risk of stroke and systemic embolism. Healey et al. investigated whether subclinical rapid atrial rate detected by implanted devices was associated with the risk of ischemic stroke in patients without clinical evidence of AF. The current article discusses the potential implications of the above results.

EP News: Clinical

Healey et al (N Engl J Med 2012;366:120–129, PMID 22236222) evaluated whether subclinical episodes of rapid atrial rate were associated with ischemic stroke in patients without other evidence of atrial fibrillation (AF). A total of 2580 patients, 65 years or older, with hypertension and no history of AF, and in whom a pacemaker or a defibrillator had been implanted were monitored to detect subclinical atrial tachyarrhythmias (AT) (episodes of atrial rate >190 beats/min for more than 6 minutes). The primary outcome was ischemic stroke or systemic embolism.

Subclinical Atrial Fibrillation and the Risk of Stroke

BackgroundOne quarter of strokes are of unknown cause, and subclinical atrial fibrillation may be a common etiologic factor. Pacemakers can detect subclinical episodes of rapid atrial rate, which correlate with electrocardiographically documented atrial fibrillation. We evaluated whether subclinical episodes of rapid atrial rate detected by implanted devices were associated with an increased risk of ischemic stroke in patients who did not have other evidence of atrial fibrillation.MethodsWe enrolled 2580 patients, 65 years of age or older, with hypertension and no history of atrial fibrillation, in whom a pacemaker or defibrillator had recently been implanted. We monitored the patients for 3 months to detect subclinical atrial tachyarrhythmias (episodes of atrial rate >190 beats per minute for more than 6 minutes) and followed them for a mean of 2.5 years for the primary outcome of ischemic stroke or systemic embolism. Patients with pacemakers were randomly assigned to receive or not to receive continuous atrial overdrive pacing.ResultsBy 3 months, subclinical atrial tachyarrhythmias detected by implanted devices had occurred in 261 patients (10.1%). Subclinical atrial tachyarrhythmias were associated with an increased risk of clinical atrial fibrillation (hazard ratio, 5.56; 95% confidence interval [CI], 3.78 to 8.17; P<0.001) and of ischemic stroke or systemic embolism (hazard ratio, 2.49; 95% CI, 1.28 to 4.85; P=0.007). Of 51 patients who had a primary outcome event, 11 had had subclinical atrial tachyarrhythmias detected by 3 months, and none had had clinical atrial fibrillation by 3 months. The population attributable risk of stroke or systemic embolism associated with subclinical atrial tachyarrhythmias was 13%. Subclinical atrial tachyarrhythmias remained predictive of the primary outcome after adjustment for predictors of stroke (hazard ratio, 2.50; 95% CI, 1.28 to 4.89; P=0.008). Continuous atrial overdrive pacing did not prevent atrial fibrillation.ConclusionsSubclinical atrial tachyarrhythmias, without clinical atrial fibrillation, occurred frequently in patients with pacemakers and were associated with a significantly increased risk of ischemic stroke or systemic embolism. (Funded by St. Jude Medical; ASSERT ClinicalTrials.gov number, NCT00256152.)

Rapid Atrial Rates and Atrio-Ventricular Dyssynchrony Predispose to Increased Thrombogenesis in the Human Left Atrium in Patients with Atrial Fibrillation

Rapid Atrial Rates and Atrio-Ventricular Dyssynchrony Predispose to Increased Thrombogenesis in the Human Left Atrium in Patients with Atrial Fibrillation

The Effect of Acute Onset Atrial Fibrillation and Rapid Atrial Rates on Markers of Thrombogenesis in the Human Left Atrium

Background: Atrial fibrillation (AF) is associated with thromboembolic stroke. The precise mechanism of thrombogenesis in the human left atrium (LA) with acute AF remains unknown.Methods: 36 AF patients in sinus rhythm undergoing catheter ablation were studied. Blood samples were taken from the LA and femoral vein immediately after transseptal puncture and 15 minutes after AF induction (14 patients), atrial pacing at 150 bpm (14 patients) and in controls (8 patients). Platelet activation (P-selectin), thrombin generation [thrombin-antithrombin (TAT) complex], endothelial dysfunction [asymmetric dimethylarginine (ADMA)] and inflammation [soluble CD40-ligand (sCD40L)] were assessed by flow cytometry and ELISA.Results: P-selectin increased significantly with both AF (14.5±5.8 baseline vs. 22.9±12.9%+ve 15 min, p<0.01) and pacing (16.2±6.8 baseline vs. 19.5±5.6%+ve 15 min, p<0.01), but decreased in controls (p<0.05). TAT increased specifically in the LA with both AF (18.4±16.6 baseline vs. 32.1±25.2 µg/L 15 min, p<0.01) and pacing (16.5±13.8 baseline vs. 49.0±46.6 µg/L 15 min, p<0.01), but decreased peripherally (p<0.01), and decreased in controls (p<0.01). With acute AF, ADMA (p<0.05) and sCD40L (p<0.01) increased significantly, not seen with pacing (p=ns) or controls (p=ns).Conclusion: Acute onset human AF and rapid atrial rates both result in increased platelet activation and thrombin generation, more pronounced in the human LA. Acute AF also induces endothelial dysfunction and inflammation. These findings suggest that while rapid atrial rates increase the thrombogenic risk, abnormal rhythm further potentiates this risk.

Knock-in gain-of-function sodium channel mutation prolongs atrial action potentials and alters atrial vulnerability

Patients with long QT syndrome (LQTS) are at increased risk not only for ventricular arrhythmias but also for atrial pathology including atrial fibrillation (AF). Some patients with "lone" AF carry Na(+)-channel mutations. The purpose of this study was to determine the mechanisms underlying atrial pathology in LQTS. In mice with a heterozygous knock-in long QT syndrome type 3 (LQT3) mutant of the cardiac Na(+) channel (ΔKPQ-SCN5A) and wild-type (WT) littermates, atrial size, function, and electrophysiologic parameters were measured in intact Langendorff-perfused hearts, and histologic analysis was performed. Atrial action potential duration, effective refractory period, cycle length, and PQ interval were prolonged in ΔKPQ-SCN5A hearts (all P < .05). Flecainide (1 μM) reversed atrial action potential duration prolongation and induced postrepolarization refractoriness (P < .05). Arrhythmias were infrequent during regular rapid atrial rate in both WT and ΔKPQ-SCN5A but were inducible in 15 (38%) of 40 ΔKPQ-SCN5A and 8 (29%) of 28 WT mice upon extrastimulation. Pacing protocols generating rapid alterations in rate provoked atrial extrasystoles and arrhythmias in 6 (66%) of 9 ΔKPQ-SCN5A but in 0 (0%) of 6 WT mice (P < .05). Atrial diameter was increased by nearly 10% in ΔKPQ-SCN5A mice > 5 months old without increase in fibrotic tissue. Murine hearts bearing an LQT3 mutation show abnormalities in atrial electrophysiology and subtle changes in atrial dimension, including an atrial arrhythmogenic phenotype on provocation. These results support clinical data suggesting that LQTS mutations can cause atrial pathology and arrhythmogenesis and indicate that murine sodium channel LQTS models may be useful for exploring underlying mechanisms.

Atrial Remodeling and Atrial Fibrillation

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It can occur at any age but is very rare in children and becomes extremely common in the elderly, with a prevalence approaching 20% in patients >85 years of age.1 AF is associated with a wide range of potential complications and contributes significantly to population morbidity and mortality. Present therapeutic approaches to AF have major limitations, including limited efficacy and significant adverse effect liability. These limitations have inspired substantial efforts to improve our understanding of the mechanisms underlying AF, with the premise that improved mechanistic insights will lead to innovative and improved therapeutic approaches.2 Our understanding of AF pathophysiology has advanced significantly over the past 10 to 15 years through an increased awareness of the role of “atrial remodeling.” Any persistent change in atrial structure or function constitutes atrial remodeling. Many forms of atrial remodeling promote the occurrence or maintenance of AF by acting on the fundamental arrhythmia mechanisms illustrated in Figure 1. Both rapid ectopic firing and reentry can maintain AF. Reentry requires a suitable vulnerable substrate, as well as a trigger that acts on the substrate to initiate reentry. Ectopic firing contributes to reentry by providing triggers for reentry induction. Atrial remodeling has the potential to increase the likelihood of ectopic or reentrant activity through a multitude of potential mechanisms. This article reviews the types of atrial remodeling, their underlying pathophysiology, the molecular basis of their occurrence, and finally, their potential therapeutic significance. Figure 1. General schema representing AF mechanisms and the role of remodeling. The mechanisms underlying AF are portrayed schematically in Figure 2. AF can be maintained by rapid focal firing, which may itself be regular but result in fibrillatory activity because of wave breakup in portions of the atrium that …

Double Dissociated Tachycardias: Isorhythmic A-V Dissociation at Rapid Atrial and Ventricular Rates

Double Dissociated Tachycardias: Isorhythmic A-V Dissociation at Rapid Atrial and Ventricular Rates

Effects of Systolic Atrial Function on Plasma Renin Activity and Natriuretic Peptide Secretion after High Rate Atrial and Ventricular Pacing in Dogs

Rapid atrial rates cause electrical, structural remodeling, and neuro-humoral changes. This study compares the effects of mechanical remodeling on plasma renin activity (PRA) and atrial natriuretic peptide (ANP) secretion. Eight beagles were subjected to rapid atrial pacing (AP) at 400 beats/min for 16 days. After complete recovery of left ventricular function, they underwent rapid ventricular pacing (VP) at 240 beats/min of equal duration. Left atrial systolic maximal dimension (LAmax) and left atrial appendage (LAA) peak late emptying velocity (LAA-E) were assessed by echocardiography. Blood samples were taken from the right atrium and from the peripheral vein. LAmax after AP and VP enlarged significantly (2.16 +/- 0.21 cm vs 2.41 +/- 0.23 cm, P = 0.002). Compared with baseline, LAA-E velocities were significantly reduced (0.65 +/- 0.12 m/s vs 0.26 +/- 0.16 m/s, P = 0.001) after AP only. AP caused a significant elevation of PRA in right atrial (9.28 +/- 4.23 nmol/L per hour) and peripheral samples compared with baseline values (4.82 +/- 2.53 nmol/L per hour, P = 0.04). ANP levels increased after AP (1117.12 +/- 252.21 fmol/L) with respect to baseline values (824.37 +/- 159.08 fmol/L, P = 0.001). There was no difference in PRA and ANP levels between atrial and peripheral samples. Atrial size and impaired systolic appendage function play an important role in secretion of PRA and ANP. Both neuro-humoral pathways may be therapeutic targets in the treatment of patients with AF.

Effect of the cardioselective, sarcolemmal K(ATP) channel blocker HMR 1098 on atrial electrical remodeling during pacing-induced atrial fibrillation in dogs.

The progressive shortening of the atrial effective refractory period (ERP) during atrial fibrillation (AF) might be due to the activation of the KATP channels by rapid atrial rates. We tested the hypothesis that the cardioselective, sarcolemmal KATP channel blocker HMR 1098 would prevent atrial ERP shortening during AF. Nine dogs were treated with HMR 1098 (3 mg/kg bolus injection followed by a continuous intravenous (i.v.) infusion at 17 microg/kg/min rate maintained throughout the study) and 7 dogs served as controls receiving i.v. saline. Pharmacological autonomic blockade was induced by i.v. administration of atropine (0.04 mg/kg) and propranolol (0.2 mg/kg) and maintained throughout the study by continuous i.v. infusion of atropine (0.007 mg/kg/h) and propranolol (0.04 mg/kg/h). Rapid right atrial pacing at 50 msec cycle length (CL) was initiated and maintained for 6 hours. High right atrial ERP (HRA-ERP) and corrected sinus node recovery time (HRA-cSNRT), coronary sinus ERP (CS-ERP) and corrected SNRT (CS-cSNRT) at three (400, 300, 200 msec) CLs were measured before and after pacing at different time points. Baseline values were not different between control and treated dogs. In the control group the HRA-ERP progressively shortened (from 179 +/- 21 msec at baseline to 161 +/- 23 msec at 360 min at 400 msec CL) ( p = 0.002), with a gradual decrease, loss or inversion of ERP rate adaptation at shorter (300, 200 msec) CLs. HMR 1098 treatment did not prevent the shortening of HRA-ERP during the first 2 to 3 hours of rapid atrial pacing. However, beginning at 180-240 min, HMR 1098 increased the HRA-ERP ( p = 0.01) to baseline by 360 min. HMR 1098 treatment did not prevent another feature of atrial electrical remodeling, the flattening or inversion of ERP rate adaptation. In neither group did CS-ERP shortening occur. The maximum cSNRT at 360 min prolonged significantly in both groups during HRA and CS pacing as well compared with baseline. HMR 1098 treatment did not prevent the shortening of HRA-ERP, the salient feature of atrial electrical remodeling in the first 2 to 3 hours of rapid atrial rates, but did prevent it thereafter. Another characteristic feature of atrial electrical remodeling, the flattening or inversion of physiological ERP rate adaptation was not prevented by HMR 1098 treatment. Sinus node depression was detectable after short-term (6 hours) rapid atrial pacing and was not affected by HMR 1098.

Molecular mechanisms of early electrical remodeling: transcriptional downregulation of ion channel subunits reduces ICa,Land Itoin rapid atrial pacing in rabbits

ObjectivesThe purpose of the study was to characterize the ionic and molecular mechanisms in the very early phases of electrical remodeling in a rabbit model of rapid atrial pacing (RAP). BackgroundLong-term atrial fibrillation reduces L-type Ca2+(ICa,L) and transient outward K+(Ito) currents by transcriptional downregulation of the underlying ionic channels. However, electrical remodeling starts early after the onset of rapid atrial rates. The time course of ion current and channel modulation in these early phases of remodeling is currently unknown. MethodsRapid (600 beats/min) right atrial pacing was performed in rabbits. Animals were divided into five groups with pacing durations between 0 and 96 h. Ionic currents were measured by patch clamp techniques; messenger ribonucleic acid (mRNA) and protein expression were measured by reverse transcription-polymerase chain reaction and Western blot, respectively. ResultsL-type calcium current started to be reduced (by 47%) after 12 h of RAP and continued to decline as pacing continued. Current changes were preceded or paralleled by decreased mRNA expression of the Ca2+channel β subunits CaB2a, CaB2b, and CaB3, whereas significant reductions in the α1subunit mRNA and protein expression began 24 h after pacing onset. Transient outward potassium current densities were not altered within the first 12 h, but after 24 h, currents were reduced by 48%. Longer pacing periods did not further decrease Ito. Current changes were paralleled by reduced Kv4.3 mRNA expression. Kv4.2, Kv1.4, and the auxiliary subunit KChIP2 were not affected. ConclusionsL-type calcium current and Itoare reduced in early phases of electrical remodeling. A major mechanism appears to be transcriptional downregulation of underlying ion channels, which partially preceded ion current changes.

Atrial fibrillation: molecular biology bases

Atrial fibrillation is the most frequent form of sustained arrhythmia. In most cases the arrhythmia is acquired, in rarer cases it may occur as a familial disease with a autosomal dominant pattern of inheritance. Recent advances in molecular biology and genetics have had a major impact on our understanding of the mechanisms responsible for the initiation, maintenance and chronification of the arrhythmia. Recently, the chromosomal locus for familial atrial fibrillation has been mapped to chromosome 10q22-q23, however, so far the causative gene has not been identified. Atrial fibrillation itself modifies atrial electrical properties in a way that promotes the occurrence and maintenance of the arrhythmia, in other words "atrial fibrillation begets atrial fibrillation". The principle stimulus for atrial remodeling is the rapid atrial rate. It is hoped that the results of future studies will not only further improve our understanding of the mechanisms underlying atrial fibrillation but may also help to develop new therapeutic strategies.

Vorhofflimmern: Pathophysiologie

Although several classical studies seemed to provide clear ideas on the pathophysiology of atrial fibrillation, current concepts have to be modified on the basis of more recent findings. Based on the findings of Garrey and of Moe & Abildskov, atrial fibrillation has long been considered as the prototype of an arrhythmia being caused by multiple, random reentrant circuits, the number of which would determine the stability of the reentrant process. Local refractory and conduction properties would determine the size of individual circuits, a hypothesis quite convincing with respect to refractoriness, but so far hard to prove with respect to conduction. The finding that rapid atrial rates shorten atrial refractory periods and reverse rate adaptation (atrial remodeling) has coined the phrase "atrial fibrillation begets atrial fibrillation", indicating that any atrial tachyarrhythmia modifies the substrate in a way that favors reentry. With intracellular calcium overload being the initial trigger, down-regulation of genes encoding for calcium channels seems to primarily account for atrial remodeling. Primarily neglected concepts on the pathophysiology of atrial fibrillation suggesting single, meandering circuits or focal activity have regained attention. Atrial fibrillation as a random phenomenon is questioned not only by the dominant role of the left atrium for the maintenance of the arrhythmia, but also by most recent data demonstrating a spatio-temporal periodicity in activation patterns. Finally, ablation studies have provided convincing evidence that there is a subset of patients with focal or at least focally induced atrial fibrillation.