Clinical mapping approach to diagnose electrical rotors and focal impulse sources for human atrial fibrillation

Computational Mapping of Rotors and Focal Impulses in Human AF. Introduction: The perpetuating mechanisms for human atrial fibrillation (AF) remain undefined. Localized rotors and focal beat sources may sustain AF in elegant animal models, but there has been no direct evidence for localized sources in human AF using traditional methods. We developed a clinical computational mapping approach, guided by human atrial tissue physiology, to reveal sources of human AF. Methods and Results: In 49 AF patients referred for ablation (62 ± 9 years; 30 persistent), we defined repolarization dynamics using monophasic action potentials (MAPs) and recorded AF activation from 64‐pole basket catheters in left atrium and, in n = 20 patients, in both atria. Careful positioning of basket catheters was required for optimal mapping. AF electrograms at 64–128 electrodes were combined with repolarization and conduction dynamics to construct spatiotemporal AF maps. We observed sustained sources in 47/49 patients, in the form of electrical rotors (n = 57) and focal beats (n = 11) that controlled local atrial activation with peripheral wavebreak (fibrillatory conduction). Patients with persistent AF had more sources than those with paroxysmal AF (2.1 ± 1.0 vs 1.5 ± 0.8, P = 0.02), related to shorter cycle length (163 ± 19 milliseconds vs 187 ± 25 milliseconds, P < 0.001). Approximately one‐quarter of sources lay in the right atrium. Conclusions: Physiologically guided computational mapping revealed sustained electrical rotors and repetitive focal beats during human AF for the first time. These localized sources were present in 96% of AF patients, and controlled AF activity. These results provide novel mechanistic insights into human AF and lay the foundation for mechanistically tailored approaches to AF ablation. (J Cardiovasc Electrophysiol, Vol. 23, pp. 447‐454, May 2012)     

Prediction of atrial fibrillation development and progression:current perspectives

Atrial fibrillation(AF) is the most common arrhythmia in clinical practice. Several conventional and novel predictors of AF development and progression(from paroxysmal to persistent and permanent types) have been reported. The most important predictor of AF progression is possibly the arrhythmia itself. The electrical, mechanical and structural remodeling determines the perpetuation of AF and the progression from paroxysmal to persistent and permanent forms. Common clinical scores such as the hypertension, age ≥ 75 years, transient ischemic attack or stroke, chronic obstructive pulmonary disease, and heart failure and the congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category scores as well as biomarkers related to inflammation may also add important information on this topic. There is now increasing evidence that even in patients with so-called lone or idiopathic AF, the arrhythmia is the manifestation of a structural atrial disease which has recently been defined and described as fibrotic atrial cardiomyopathy. Fibrosis results from a broad range of factors related to AF inducing pathologies such as cell stretch, neurohumoral activation, and oxidative stress. The extent of fibrosis as detected either by late gadolinium enhancement-magnetic resonance imaging or electroanatomic voltage mapping may guide the therapeutic approach based on the arrhythmia substrate. The knowledge of these risk factors may not only delay arrhythmia progression, but also reduce the arrhythmia burden in patients with first detected AF. The present review highlights on the conventional and novel risk factors of development and progression of AF.     

Reproducibility of spontaneous initiations of atrial fibrillation.

INTRODUCTION: It has been suggested that some atrial regions may play a role in the maintenance of atrial fibrillation (AF), whereas little is known about the presence of critical areas for the initiation of AF. It is conceivable that the identification of such critical areas may lead to more localized and selective strategies of ablative therapy. METHODS AND RESULTS: A patient suffering from paroxysmal AF was extensively mapped in both the atria with a multielectrode basket catheter in right atrium and two decapolar catheters placed in the coronary sinus and along the left septum. During the mapping, seven identical patterns of initiation of AF were recorded. AF was initiated by an atrial premature beat (APB) arising from the superior right septum, followed by a reentrant beat originating from the same area that slowly propagated through the atria and resulted in late activation of the right lateral wall. During sinus rhythm, the majority of the electrograms were single potentials, whereas during the APB, and particularly during the first atrial reentrant beat, a high percentage of fragmented complexes was present, mainly located in the right superior septum. These fragmented complexes were present in the same sites in each initiating episode and remarkably, they showed an almost identical morphology. CONCLUSION: This case suggests that in some patients the initiation of AF could be caused by reentrant circuits localized in specific atrial regions and the reentrant circuits could be identical in the different episodes of AF. This highlights the importance of increasing our understanding of the mechanisms of the initiation of AF so that we can identify any critical area involved in the genesis of AF where selective RF lesions may be effective in curing this arrhythmia.     

Mapping and ablating stable sources for atrial fibrillation: summary of the literature on Focal Impulse and Rotor Modulation (FIRM)

Atrial fibrillation (AF) is the most common sustained arrhythmia and the most common indication for catheter ablation. However, despite substantial technical advances in mapping and energy delivery, ablation outcomes remain suboptimal. A major limitation to AF ablation is that the areas targeted for ablation are rarely of proven mechanistic importance, in sharp contrast to other arrhythmias in which ablation targets demonstrated mechanisms in each patient. Focal impulse and rotor modulation (FIRM) is a new approach to demonstrate the mechanisms that sustain AF (“substrates”) in each patient that can be used to guide ablation then confirm elimination of each mechanism. FIRM mapping reveals that AF is sustained by 2–3 rotors and focal sources, with a greater number in patients with persistent than paroxysmal AF, lying within spatially reproducible 2.2?±?1.4-cm² areas in diverse locations. This temporospatial reproducibility, now confirmed by several groups using various methods, changes the concepts regarding AF-sustaining mechanisms, enabling localized rather than widespread ablation. Mechanistically, the role of rotors and focal sources in sustaining AF has been demonstrated by the acute and chronic success of source (FIRM) ablation alone. Clinically, adding FIRM to conventional ablation substantially improves arrhythmia freedom compared with conventional ablation alone, and ongoing randomized trials are comparing FIRM—ablation with and without conventional ablation to conventional ablation alone. In conclusion, ablation of patient-specific AF-sustaining mechanisms (substrates), as exemplified by FIRM, may be central to substantially improving AF ablation outcomes.     

Katheterablation des Vorhofflimmerns

Atrial fibrillation (AF), the most frequently encountered sustained cardiac arrhythmia, contributes significantly to population morbidity and mortality and is associated with heart failure and stroke. Catheter ablation of AF is an effective tool to treat symptomatic paroxysmal AF. In patients with persistent AF and/or cardiac disease, however, ablation tends to be more challenging with substrate modification strategies playing a major role in many cases. Novel technologies and concepts (e.g., alternative energy sources, remote robotic catheter navigation, elimination of localized re-entrant waves or “rotors”, and gene therapy) have been developed to reduce the AF recurrence rate and are currently under evaluation at different stages of clinical and experimental studies. Long-term continuation of oral anticoagulant therapy is required post-ablation irrespective of the procedural success in all patients with a CHA₂DS₂-VASc score of ≥?2. Finally, ongoing clinical trials are investigating potential effects of AF ablation on morbidity and mortality and on left ventricular ejection fraction in patients with heart failure.     

Adjunct ablation strategies for persistent atrial fibrillation—beyond pulmonary vein isolation

Atrial fibrillation (AF) is the most common sustained arrhythmia. Recent guidelines recommend pulmonary vein isolation (PVI) as the main procedural endpoint to control recurrent AF in symptomatic patients resistant to antiarrhythmic drugs. The efficacy of such procedure is higher in paroxysmal AF while is still unsatisfactory in persistent and long-standing persistent AF. This review will summarize the state-of-the-art of AF ablation techniques in patients with persistent AF, discussing the evidence underlying different approaches with a particular focus on adjunctive ablation strategies beyond PVI including linear ablation, ablation of complex fractionated atrial electrograms (CFAE), ablation of ganglionated plexi, dominant frequency, rotors and other anatomical sites frequently involved in AF triggers.     

Toward discerning the mechanisms of atrial fibrillation from surface electrocardiogram and spectral analysis

Atrial fibrillation (AF) is the main cause of stroke and the most common sustained arrhythmia, afflicting about 2.3 million Americans. Clinical treatment and management of AF would benefit from a noninvasive and global assessment of the arrhythmia; however, that avenue seems currently limited in part by our poor understanding of arrhythmia itself. Experimental studies of AF in the isolated sheep heart demonstrated that high-frequency sources in the posterior wall of the left atrium drive the fibrillatory activity throughout both atria. Motivated by those results and by a growing body of work investigating how measurements of the cycle length of activity in patients during AF can contribute to its treatment, we focused our analysis on the dispersion of dominant frequency (DF) of the activity during AF in humans. Using electroanatomic mapping and Fourier methods, we generated 3-dimensional intracardiac DF maps of the atria in patients before AF ablation procedures and identified relatively small high-DF (HDF) sites. In patients with paroxysmal AF, the HDF sites are often localized to the posterior left atrium near the ostia of the pulmonary veins. In contrast, patients with permanent AF demonstrate HDF sites that are more often localized to the atria than the posterior left atrium-pulmonary vein junction. In our study, ablation at HDF sites resulted in significant slowing of the arrhythmia and termination of sustained AF in 87% of patients with paroxysmal AF. Furthermore, we found that abolishing, by ablation, preexisting left atrium to right atrium DF gradients predicted long-term freedom of AF in both paroxysmal and persistent AF patients. Overall, the analysis of intracardiac electrical recordings in the frequency domain has greatly enhanced our understanding of its underlying mechanisms and may contribute to monitoring drug effects and guide ablation procedures aiming at its termination. On the other hand, current body surface mapping methods have also suggested better correlations between surface AF frequency and intracardiac local DFs as compared with spatiotemporal activation patterns. Therefore, further study of the correlation of spectral observables obtained from the atria and from the surface electrocardiogram during AF seems to have the potential to advance our ability to diagnose and discern mechanisms of AF noninvasively.     

Acute Termination of Human Atrial Fibrillation by Identification and Catheter Ablation of Localized Rotors and Sources: First Multicenter Experience of Focal Impulse and Rotor Modulation (FIRM) Ablation

FIRM Ablation of Human AF Rotors. Introduction: Catheter ablation of atrial fibrillation (AF) currently relies on eliminating triggers, and no reliable method exists to map the arrhythmia itself to identify ablation targets. The aim of this multicenter study was to define the use of Focal Impulse and Rotor Modulation (FIRM) for identifying ablation targets. Methods: We prospectively enrolled the first (n = 14, 11 males) consecutive patients undergoing FIRM‐guided ablation for persistent (n = 11) and paroxysmal AF at 5 centers. A 64‐pole basket catheter was used for panoramic right and left atrial mapping during AF. AF electrograms were analyzed using a novel system to identify sustained rotors (spiral waves), or focal beats (centrifugal activation to surrounding atrium). Ablation was performed first at identified sources. The primary endpoints were acute AF termination or organization (>10% cycle length prolongation). Conventional ablation was performed only after FIRM‐guided ablation. Results: Twelve out of 14 cases were mapped. AF sources were demonstrated in all patients (average of 1.9 ± 0.8 per patient). Sources were left atrial in 18 cases, and right atrial in 5 cases, and 21/23 were rotors. FIRM‐guided ablation achieved the acute endpoint in all patients, consisting of AF termination in n = 8 (4.9 ± 3.9 minutes at the primary source), and organization in n = 4. Total FIRM time for all patients was 12.3 ± 8.6 minutes. Conclusions: FIRM‐guided ablation revealed localized AF rotors/focal sources in patients with paroxysmal, persistent and longstanding persistent AF. Brief targeted FIRM‐guided ablation at a priori identified sites terminated or substantially organized AF in all cases prior to any other ablation. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1277‐1285, December 2012)     

Pulmonary vein triggers,focal sources,rotors and atrial cardiomyopathy: implications for the choice of the most effective ablation therapy

Understanding of the pathophysiological mechanism(s) underlying atrial fibrillation (AF) is the foundation on which current ablation strategies are built. In the vast majority of patients with paroxysmal AF, the ablation procedure should target the pulmonary veins. In patients with nonparoxysmal AF, however, pulmonary vein isolation alone seems to be insufficient to prevent the arrhythmia. Several recent clinical trials have investigated the concept that rotors (re‐entry based on a meandering central core from which spiral waves emanate) might be the mechanism responsible for sustaining AF. Ablation of these localized AF sources is an important step towards substrate‐driven procedures in persistent AF. Hybrid AF ablation procedures, based on the integration of endocardial transcatheter and epicardial off‐pump surgical techniques, have been introduced to overcome their mutual shortcomings. The long‐term results are encouraging, especially in currently challenging settings such as nonparoxysmal AF and failed endocardial catheter ablation procedures.     

Ibutilide added to propafenone for the conversion of atrial fibrillation and atrial flutter

OBJECTIVES: We evaluated the safety and efficacy of ibutilide when added to propafenone in treating both paroxysmal and chronic atrial fibrillation (AF) and atrial flutter (AFL). BACKGROUND: The effects of ibutilide in patients with paroxysmal or chronic AF/AFL who were pre-treated with propafenone have not been previously evaluated. METHODS: Oral propafenone was initially given in 202 patients with AF/AFL without left ventricular dysfunction. Intravenous ibutilide was administered in 104 patients in whom propafenone failed to convert the arrhythmia. Two different propafenone dosage regimens were used according to the duration of the presenting arrhythmia: patients with paroxysmal arrhythmia (n = 48) received 600 mg loading dose, and patients with chronic arrhythmia (n = 56) were receiving 150 mg three times a day as stable-dose pre-treatment. RESULTS: Ibutilide offered an overall conversion efficacy of 66.3% (69 of 104 patients), 70.8% for patients with paroxysmal AF/AFL and 62.5% for patients with chronic AF/AFL. Ibutilide significantly decreased the heart rate (HR) and further prolonged the QTc interval (p < 0.0001). The degree of HR reduction after ibutilide administration emerged as the sole predictor of successful arrhythmia termination (p < 0.001). After ibutilide, one patient (1%) developed two asymptomatic episodes of non-sustained torsade de pointes, and 10 patients (9.6%) manifested transient bradyarrhythmic events; however, all bradyarrhythmic effects were predictable, occurring mostly at the time of arrhythmia termination. None of 82 patients who decided to continue propafenone after successful cardioversion had immediate arrhythmia recurrence. CONCLUSIONS: Our graded approach using propafenone and ibutilide appears to be a relatively safe and effective alternative for the treatment of paroxysmal and chronic AF/AFL to both rapidly restore sinus rhythm in nonresponders to monotherapy with propafenone and prevent immediate recurrences of the arrhythmia.     

A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate

OBJECTIVES: We sought to test the hypothesis that complex fractionated electrograms (CFAEs) recorded during atrial fibrillation (AF) could be used as target sites for catheter ablation of AF. BACKGROUND: Mapping of AF in humans has shown that areas of CFAEs correlate with areas of slowed conduction and pivot points of reentrant wavelets. We hypothesized that such areas of CFAEs could be identified in patients with AF and might serve as target sites for catheter ablation to maintain sinus rhythm. METHODS: The study population included 121 patients (29 females; mean age, 63 years) with refractory AF (57 paroxysmal, 64 chronic). All patients underwent nonfluoroscopic electroanatomic mapping (CARTO) during AF. Using CARTO, the biatrial replica, displayed in a three-dimensional color-coded voltage map, was created during AF, and areas associated with CFAEs were identified. Radiofrequency ablation of the area with CFAEs was performed, aiming to eliminate CFAE and/or convert to sinus rhythm. RESULTS: Complex fractionated atrial electrograms were found in seven of nine regions of both atria, but were mainly confined to the interatrial septum, pulmonary veins, roof of left atrium, and left posteroseptal mitral annulus and coronary sinus ostium. Ablations of the areas associated with CFAEs resulted in termination of AF without external cardioversion in 115 of the 121 patients (95%); 32 (28%) required concomitant ibutilide treatment. At the one-year follow-up, 110 (91%) patients were free of arrhythmia and symptoms, 92 after one ablation and 18 after two. CONCLUSIONS: Areas with CFAEs represent a defined electrophysiologic substrate and are ideal target sites for ablations to eliminate AF and maintain normal sinus rhythm.     

Rotors and spiral waves in atrial fibrillation

Despite many years of research, the mechanisms of atrial fibrillation (AF) are still poorly understood, and we currently are unable to adequately treat most patients with AF. Recently, the demonstration in both human and animal studies that the pulmonary veins (PVs) and the posterior left atrial (LA) wall play a substantial role in triggering and in driving the fibrillatory activity has opened new avenues for research into the mechanisms of initiation and maintenance AF at many levels of integration. This article focuses on recent studies at the whole-heart level that support the hypothesis that maintenance of AF, whether paroxysmal or persistent, may depend on the periodic activity of a small number of rotors in the posterior LA wall-PV region. These rotors activate the atria at exceedingly high frequencies and result in fibrillatory conduction. Recent clinical studies involving either segmental PV isolation or circumferential PV ablation support this view. Such encouraging results suggest that collaboration between basic and clinical electrophysiologists will lead to a more precise understanding of the manner in which rotors stabilize in the PV-LA junction, which should open new doors for the development of innovative approaches for the prevention, diagnosis, and treatment of AF.     

An epidemiological study of symptomatic paroxysmal atrial fibrillation in northwest Greece.

AIM: Although atrial fibrillation (AF) is the most commonly sustained arrhythmia, information about its incidence in the general population is sparse. Even more sparse is information on an important variety of AF, paroxysmal AF. The aim of this study is to assess the frequency of new cases of symptomatic paroxysmal AF per year ('incidence') in a general unselected population and to compare other epidemiological features with chronic AF patients. METHODS AND RESULTS: Over a 4 year period, we conducted a prospective, population-based survey of cases of AF in a defined geographical area with a known population size stratified for age and sex. Sources of identification were the two hospitals which serve the area and all the primary care settings. Patients with AF of less than 7 days duration were characterized as paroxysmal AF and all others as chronic AF. During the study period we identified 1551 patients with chronic AF (51.7% male, mean age 71 +/- 10.4 years and 48.3% females, mean age 73.1 +/- 10.8 years) and 443 patients with paroxysmal AF (59.6% male, mean age 59.6 +/- 13.3 years and 40.4% female, mean age 65.2 +/- 10.1 years). There was no underlying cardiovascular disease in 15.6% and 32.3% of patients with chronic and paroxysmal AF, respectively. The mean annual occurrence of new cases of paroxysmal AF was 6.2/10,000/year, and was higher (P<0.01) for men (7.2/10,000/year) than for women (5.3/10,000/year). The frequency of new paroxysmal AF cases rises with age, reaching a peak at 70-79 years and then declines. CONCLUSIONS: We conclude that paroxysmal AF is a relatively common arrhythmia, the occurrence of which increases with age and is more frequent in younger men than in women. Patients with chronic AF are older and more often have underlying heart and other disease than patients with paroxysmal AF.     

Cardiac Sarcoidosis

Atrial fibrillation (AF) is the most common arrhythmia targeted by catheter ablation. Despite significant advances in our understanding of AF, ablation outcomes remain suboptimal, and this is due in large part to an incomplete understanding of the underlying sustaining mechanisms of AF. Recent developments of patient-tailored and physiology-based computational mapping systems have identified localized electrical spiral waves, or rotors, and focal sources as mechanisms that may represent novel targets for therapy. This report provides an overview of Focal Impulse and Rotor Modulation (FIRM) mapping, which reveals that human AF is often not actually driven by disorganized activity but instead that disorganization is secondary to organized rotors or focal sources. Targeted ablation of such sources alone can eliminate AF and, when added to pulmonary vein isolation, improves long-term outcome compared with conventional ablation alone. Translating mechanistic insights from such patient-tailored mapping is likely to be crucial in achieving the next major advances in personalized medicine for AF.     

Mechanisms of atrial fibrillation: lessons from studies in patients

Recent clinical studies performed in human subjects have provided important clues that improved our understanding of the mechanisms of atrial fibrillation (AF) and facilitated development of new treatment strategies. When analyzed together, these studies confirm the complexity and multifactorial nature of AF. Because a variety of mechanisms such as focal drivers within the thoracic veins, rotors in the left atrium, multiple reentrant circuits, and autonomic innervation may play a role in the initiation and maintenance of AF alone or in combination, the best strategy to eliminate AF may be the accurate identification of one or more of the mechanisms critical to the genesis of AF and to target the specific mechanism(s).     

房室折返性心动过速合并阵发性心房颤动的射频导管消融策略

目的探讨房室折返性心动过速（AVRT）合并阵发性心房颤动的射频导管消融（下称消融）策略。方法对经电生理检查证实的AVRT患者15例行旁道消融术,其中男性9例,女性6例,并对术后心房颤动的转归进行12～36个月的随访,观察心房颤动发生、持续时间、有无心律失常等情况。结果13例未再发生心房颤动,2例有严重器质性心脏病的患者仍有阵发性心房颤动复发,但发作次数明显减少,口服胺碘酮可控制症状。1例动态心电图示频发房性期前收缩。结论AVRT与阵发性心房颤动发生率增高密切相关,AVRT是心房颤动的触发因素。旁道消融后,阵发性心房颤动可明显改善,未改善者与心房扩大等心房基质未改善有关。     

持续性心房纤颤的辅助消融策略

心房纤颤（简称房颤）是一种临床上最常见的持续性心律失常,发病率高,危害大。近年来,房颤的非药物治疗取得了较快发展,其中肺静脉隔离（PVI）就是一种有效的治疗方法。这种方法对于阵发性房颤患者治愈率较高,而在持续性房颤和长时程房颤患者中疗效一般。本综述主要探讨针对持续性房颤患者的最新辅助消融策略及其机制,包括线性消融、复杂碎裂心房电位（CFAE）消融、神经节（丛）消融、主频率消融、转子消融和与房颤触发相关的其他解剖位点消融。     

Epicardial foci of atrial arrhythmias apparently originating in the left pulmonary veins

INTRODUCTION: Epicardial potential sources of atrial arrhythmias, such as the ligament of Marshall, are in close proximity with, and electrically connected to, the left superior pulmonary vein. Ectopic activity arising from these areas may be difficult to differentiate from ectopy that, according to endocardial only mapping, originates in the left superior pulmonary vein. We hypothesized that in patients with paroxysmal atrial fibrillation (AF) apparently originating in the left pulmonary veins, mapping through the distal coronary sinus might identify possible epicardial locations of the arrhythmogenic focus. METHODS AND RESULTS: Forty patients (age 48 +/- 12 years) who underwent catheter ablation for paroxysmal AF were studied by epicardial mapping through the distal, superoposterior coronary sinus. Catheterization of the distal coronary sinus in order to approach the ostium of the left superior pulmonary vein was feasible in 14 of 19 patients with AF originating in the left superior vein (11 patients) or inferior pulmonary vein (3 patients) according to endocardial mapping criteria. In 2 patients, the sole focus of atrial tachycardia/fibrillation was epicardial with earliest activation clearly preceding electrograms recorded at the os of the left superior pulmonary vein or any other endocardial mapping site. Epicardial potentials separated from atrial electrograms were present during sinus rhythm in both patients and during atrial tachycardia in one patient. Catheter ablation through the coronary sinus rendered the arrhythmia noninducible in both patients without abolishing epicardial potentials in one of them. CONCLUSION: In patients with paroxysmal AF apparently originating from the left superior or inferior pulmonary vein, detailed epicardial mapping through the distal coronary sinus might identify epicardial locations of the arrhythmogenic focus.