Pathophysiology of atrial fibrillation: Focal patterns of activation.

For decades, electrical activity recorded has been investigated to unravel pathophysiology of cardiac arrhythmias, such as atrial fibrillation (AF). Particularly high-resolution mapping studies have significantly contributed to novel insights into AF mechanisms. From these mapping studies, it appeared that persistence of AF is associated with a high incidence of focal patterns of activation. Features of these focal activation patterns indicated that they could be attributed to transmural propagation of fibrillation waves. However, "focal fibrillation waves" can only appear when there is electrical asynchrony between the endocardial and epicardial layer. By performing simultaneous high-resolution mapping of the endo- and epicardial wall of the right atrium in humans during AF, the existence of electrical asynchrony (endo-epicardial asynchrony [EEA]) between the endo- and epicardial layer was indeed confirmed. During sinus rhythm, focal patterns of activation are most frequently observed at the right atrium and a considerable degree of EEA-as large as 50 ms-may occur. Furthermore, prematurely aberrant atrial extrasystoles emerging as focal waves caused the highest degree of conduction disorders, particularly in patients with left atrial dilatation and diabetes mellitus. These observations emphasize the contribution of atrial anatomy to EEA and the role of focal patterns of activation in development AF.

Spatial distribution of conduction disorders during sinus rhythm.

BACKGROUND: Length of lines of conduction block (CB) during sinus rhythm (SR) at Bachmann's bundle (BB) is associated with atrial fibrillation (AF). However, it is unknown whether extensiveness of CB at BB represents CB elsewhere in the atria. We aim to investigate during SR 1) the spatial distribution and extensiveness of CB 2) whether there is a predilection site for CB and 3) the association between CB and incidence of post-operative AF. METHODS: During SR, epicardial mapping of the right atrium (RA), BB and left atrium was performed in 209 patients with coronary artery disease. The amount of conduction delay (CD, Δlocal activation time ≥7ms) and CB (Δ≥12ms) was quantified as % of the mapping area. Atrial regions were compared to identify potential predilection sites for CD/CB. Correlations between CD/CB and clinical characteristics were tested. RESULTS: Areas with CD or CB were present in all patients, overall prevalence was respectively 1.4(0.2-4.0) % and 1.3(0.1-4.3) %. Extensiveness and spatial distribution of CD/CB varied considerably, however occurred mainly at the superior intercaval RA. Of all clinicalcharacteristics, CD/CB only correlated weakly with age and diabetes (P<0.05). A 1% increase in CD or CB caused a 1.1-1.5ms prolongation of the activation time (P<0.001). There was no correlation between CD/CB and post-operative AF. CONCLUSION: CD/CB during SR in CABG patients with electrically non-remodeled atria show considerable intra-atrial, but also inter-individual variation. Despite these differences, a predilection site is present at the superior intercaval RA. Extensiveness of CB at the superior intercaval RA or BB does not reflect CB elsewhere in the atria and is not associated with post-operative AF.

Relevance of Conduction Disorders in Bachmann's Bundle During Sinus Rhythm in Humans.

BACKGROUND: Bachmann's bundle (BB) is considered to be the main route of interatrial conduction and to play a role in development of atrial fibrillation (AF). The goals of this study are to characterize the presence of conduction disorders in BB during sinus rhythm and to study their relation with AF. METHODS AND RESULTS: High-resolution epicardial mapping (192 unipolar electrodes, interelectrode distance: 2 mm) of sinus rhythm was performed in 185 patients during coronary artery bypass surgery of whom 13 had a history of paroxysmal AF. Continuous rhythm monitoring was used to detect postoperative AF during the first 5 postoperative days. In 67% of the patients, BB was activated from right to left; in the remaining patients from right and middle (21%), right, central, and left (8%), or central (4%) site. Mean effective conduction velocity was 89 cm/s. Conduction block was present in most patients (75%; median 1.1%, range 0-12.8) and was higher in patients with paroxysmal AF compared with patients without a history of AF (3.2% versus 0.9%; P=0.03). A high amount of conduction block (>4%) was associated with de novo postoperative AF (P=0.02). Longitudinal lines of conduction block >10 mm were also associated with postoperative AF (P=0.04). CONCLUSIONS: BB may be activated through multiple directions, but the predominant route of conduction is from right to left. Conduction velocity across BB is around 90 cm/s. Conduction is blocked in both longitudinal and transverse direction in the majority of patients. Conduction disorders, particularly long lines of longitudinal conduction block, are more pronounced in patients with AF episodes.

Dynamics of Endo- and Epicardial Focal Fibrillation Waves at the Right Atrium in a Patient With Advanced Atrial Remodelling.

Focal waves appear frequently at the epicardium during persistent atrial fibrillation (AF), however, the origin of these waves is under debate. We performed simultaneous endo-epicardial mapping of the right atrial wall during longstanding persistent AF in a patient undergoing cardiac surgery. During 10 seconds 53 and 59 focal waves appeared at random at respectively the endocardium and epicardium. Repetitive focal activity did not last longer than 3 cycles. Transmural asynchrony and conduction might be the origin of focal waves. Asynchronous propagation of fibrillation waves in 3 dimensions would stabilize the arrhythmia and could explain the limited success of persistent AF ablation.

QUest for the Arrhythmogenic Substrate of Atrial fibRillation in Patients Undergoing Cardiac Surgery (QUASAR Study): Rationale and Design.

The heterogeneous presentation and progression of atrial fibrillation (AF) implicate the existence of different pathophysiological processes. Individualized diagnosis and therapy of the arrhythmogenic substrate underlying AF may be required to improve treatment outcomes. Therefore, this single-center study aims to identify the arrhythmogenic areas underlying AF by intra-operative, high-resolution, multi-site epicardial mapping in 600 patients with different heart diseases. Participants are divided into 12 groups according to the underlying heart diseases and presence of prior AF episodes. Mapping is performed with a 192-electrode array for 5-10 s during sinus rhythm and (induced) AF of the entire atrial surface. Local activation times are converted into activation and wave maps from which various electrophysiological parameters are derived. Postoperative cardiac rhythm registrations and a 5-year follow-up will show the incidence of postoperative and persistent AF. This project provides the first step in the development of a tool for individual AF diagnosis and treatment.

Dynamics of Focal Fibrillation Waves during Persistent Atrial Fibrillation.

The incidence and appearance of focal fibrillation waves on the right and left atrial epicardial surface were visualized during 10 seconds of persistent atrial fibrillation in a 71-year-old woman with valvular heart disease. The frequent, nonrepetitive, widespread, and capricious distribution of focal waves suggests that transmural conduction of fibrillation waves is most likely the mechanism underlying focal fibrillation waves.

HALT & REVERSE: Hsf1 activators lower cardiomyocyt damage; towards a novel approach to REVERSE atrial fibrillation.

BACKGROUND: Atrial fibrillation is a progressive arrhythmia, the exact mechanism underlying the progressive nature of recurrent AF episodes is still unknown. Recently, it was found that key players of the protein quality control system of the cardiomyocyte, i.e. Heat Shock Proteins, protect against atrial fibrillation progression by attenuating atrial electrical and structural remodeling (electropathology). HALT & REVERSE aims to investigate the correlation between electropathology, as defined by endo- or epicardial mapping, Heat Shock Protein levels and development or recurrence of atrial fibrillation following pulmonary vein isolation, or electrical cardioversion or cardiothoracic surgery. STUDY DESIGN: This study is a prospective observational study. Three separate study groups are defined: (1) cardiothoracic surgery, (2) pulmonary vein isolation and (3) electrical cardioversion. An intra-operative high-resolution epicardial (group 1) or endocardial (group 2) mapping procedure of the atria is performed to study atrial electropathology. Blood samples for Heat Shock Protein determination are obtained at baseline and during the follow-up period at 3 months (group 2), 6 months (groups 1 and 2) and 1 year (group 1 and 2). Tissue samples of the right and left atrial appendages in patients in group 1 are analysed for Heat Shock Protein levels and for tissue characteristics. Early post procedural atrial fibrillation is detected by continuous rhythm monitoring, whereas late post procedural atrial fibrillation is documented by either electrocardiogram or 24-h Holter registration. CONCLUSION: HALT & REVERSE aims to identify the correlation between Heat Shock Protein levels and degree of electropathology. The study outcome will contribute to novel diagnostic tools for the early recognition of clinical atrial fibrillation. TRIAL REGISTRATIONS: Rotterdam Medical Ethical Committee MEC-2014-393, Dutch Trial Registration NTR4658.

A novel intra-operative, high-resolution atrial mapping approach.

PURPOSE: A new technique is demonstrated for extensive high-resolution intra-operative atrial mapping that will facilitate the localization of atrial fibrillation (AF) sources and identification of the substrate perpetuating AF. METHODS: Prior to the start of extra-corporal circulation, a 8 × 24-electrode array (2-mm inter-electrode distance) is placed subsequently on all the right and left epicardial atrial sites, including Bachmann's bundle, for recording of unipolar electrograms during sinus rhythm and (induced) AF. AF is induced by high-frequency pacing at the right atrial free wall. A pacemaker wire stitched to the right atrium serves as a reference signal. The indifferent pole is connected to a steal wire fixed to subcutaneous tissue. Electrograms are recorded by a computerized mapping system and, after amplification (gain 1000), filtering (bandwidth 0.5-400 Hz), sampling (1 kHz) and analogue to digital conversion (16 bits), automatically stored on hard disk. During the mapping procedure, real-time visualization secures electrogram quality. Analysis will be performed offline. RESULTS: This technique was performed in 168 patients of 18 years and older, with coronary and/or structural heart disease, with or without AF, electively scheduled for cardiac surgery and a ventricular ejection fraction above 40 %. The mean duration of the entire mapping procedure including preparation time was 9 ± 2 min. Complications related to the mapping procedure during or after cardiac surgery were not observed. CONCLUSIONS: We introduce the first epicardial atrial mapping approach with a high resolution of ≥1728 recording sites which can be performed in a procedure time of only 9±2 mins. This mapping technique can potentially identify areas responsible for initiation and persistence of AF and hopefully can individualize both diagnosis and therapy of AF.

Diagnosis and Therapy of Atrial Fibrillation: The Past, The Present and The Future.

Atrial fibrillation (AF) is the most common age-related cardiac arrhythmia. It is a progressive disease, which makes treatment difficult. The progression of AF is caused by the accumulation of damage in cardiomyocytes which makes the atria more vulnerable for AF. Especially structural remodeling and electrical remodeling, together called electropathology are sustainable in the atria and impair functional recovery to sinus rhythm after cardioversion. The exact electropathological mechanisms underlying persistence of AF are at present unknown. High resolution wavemapping studies in patients with different types of AF showed that longitudinal dissociation in conduction and epicardial breakthrough were the key elements of the substrate of longstanding persistent AF. A double layer of electrically dissociated waves propagating transmurally can explain persistence of AF (Double Layer Hypothesis) but the molecular mechanism is unknown. Derailment of proteasis -defined as the homeostasis in protein synthesis, folding, assembly, trafficking, guided by chaperones, and clearance by protein degradation systems - may play an important role in remodeling of the cardiomyocyte. As current therapies are not effective in attenuating AF progression, step-by-step analysis of this process, in order to identify potential targets for drug therapy, is essential. In addition, novel mapping approaches enabling assessment of the degree of electropathology in the individual patient are mandatory to develop patient-tailored therapies. The aims of this review are to 1) summarize current knowledge of the electrical and molecular mechanisms underlying AF 2) discuss the shortcomings of present diagnostic instruments and therapeutic options and 3) to present potential novel diagnostic tools and therapeutic targets.

Tachycardia-induced silencing of subcellular Ca2+ signaling in atrial myocytes.

Atrial fibrillation (AF) is characterized by sustained high atrial activation rates and arrhythmogenic cellular Ca2+ signaling instability; however, it is not clear how a high atrial rate and Ca2+ instability may be related. Here, we characterized subcellular Ca2+ signaling after 5 days of high atrial rates in a rabbit model. While some changes were similar to those in persistent AF, we identified a distinct pattern of stabilized subcellular Ca2+ signaling. Ca2+ sparks, arrhythmogenic Ca2+ waves, sarcoplasmic reticulum (SR) Ca2+ leak, and SR Ca2+ content were largely unaltered. Based on computational analysis, these findings were consistent with a higher Ca2+ leak due to PKA-dependent phosphorylation of SR Ca2+ channels (RyR2s), fewer RyR2s, and smaller RyR2 clusters in the SR. We determined that less Ca2+ release per [Ca2+]i transient, increased Ca2+ buffering strength, shortened action potentials, and reduced L-type Ca2+ current contribute to a stunning reduction of intracellular Na+ concentration following rapid atrial pacing. In both patients with AF and in our rabbit model, this silencing led to failed propagation of the [Ca2+]i signal to the myocyte center. We conclude that sustained high atrial rates alone silence Ca2+ signaling and do not produce Ca2+ signaling instability, consistent with an adaptive molecular and cellular response to atrial tachycardia.

Transmural conduction is the predominant mechanism of breakthrough during atrial fibrillation: evidence from simultaneous endo-epicardial high-density activation mapping.

BACKGROUND: Endo-epicardial dissociation (EED) of electric activations resulting in transmural conduction of fibrillation waves (breakthroughs) has been postulated to contribute to the complexity of the substrate of atrial fibrillation (AF). The aim of this study was to elucidate the correlation between EED and incidence of breakthrough and to test the plausibility of transmural conduction versus ectopic focal discharges as sources of breakthrough. METHODS AND RESULTS: We analyzed high-resolution simultaneous endo-epicardial in vivo mapping data recorded in left atrial free walls of goats with acute AF, 3 weeks and 6 months of AF (all n=7). Waves were analyzed for number, size, and width and categorized according to their origin outside (peripheral wave) or within the mapping area (breakthrough). Breakthrough incidence was lowest (2.1±1.0%) in acute AF, higher (11.4±6.1%) after 3 weeks (P<0.01 versus acute AF) and highest (14.2±3.8%) after 6 months AF (P<0.001 versus acute AF) and similar in the epicardium and endocardium. Most of the breakthroughs (86%; n=564) could be explained by transmural conduction, whereas only 13% (n=85) could be explained by ectopic focal discharges. Transmural microreentry did not play a role as source of breakthrough. CONCLUSIONS: This is the first study to present simultaneous endo-epicardial in vivo mapping data at sites of breakthrough events. Breakthrough incidence and degree of EED increased with increasing AF substrate complexity. In goat left atrial free walls, most of the breakthroughs can be explained by transmural conduction, whereas ectopic focal discharges play a limited role as source of breakthrough.

Electrophysiological effects of acute atrial stretch on persistent atrial fibrillation in patients undergoing open heart surgery.

BACKGROUND: The electrophysiologic effects of acute atrial dilatation and dedilatation in humans with chronic atrial fibrillation remains to be elucidated. OBJECTIVE: To study the electrophysiological effects of acute atrial dedilatation and subsequent dilatation in patients with long-standing persistent atrial fibrillation (AF) with structural heart disease undergoing elective cardiac surgery. METHODS: Nine patients were studied. Mean age was 71 ± 10 years, and left ventricular ejection was 46% ± 6%. Patients had at least moderate mitral valve regurgitation and dilated atria. After sternotomy and during extracorporal circulation, mapping was performed on the beating heart with 2 multielectrode arrays (60 electrodes each, interelectrode distance 1.5 mm) positioned on the lateral wall of the right atrium (RA) and left atrium (LA). Atrial pressure and size were altered by modifying extracorporal circulation. AF electrograms were recorded at baseline after dedilation and after dilatation of the atria afterward. RESULTS: At baseline, the median AF cycle length (mAFCL) was 184 ± 27 ms in the RA and 180 ± 17 ms in the LA. After dedilatation, the mAFCL shortened significantly to 168 ± 13 ms in the RA and to 168 ± 20 ms in the LA. Dilatation lengthened mAFCL significantly to 189 ± 17 ms in the RA and to 185 ± 23 ms in the LA. Conduction block (CB) at baseline was 14.3% ± 3.6% in the RA and 17.3% ± 5.5% in the LA. CB decreased significantly with dedilatation to 7.4% ± 2.9% in the RA and to 7.9% ± 6.3% in the LA. CB increased significantly with dilatation afterward to 15.0% ± 8.3% in the RA and to 18.5% ± 16.0% in the LA. CONCLUSIONS: Acute dedilatation of the atria in patients with long-standing persistent AF causes a decrease in the mAFCL in both atria. Subsequent dilatation increased the mAFCL. The amount of CB decreased with dedilatation and increased with dilatation afterward in both atria.

Aldosterone promotes atrial fibrillation.

AIMS: Hyperaldosteronism is associated with an increased prevalence of atrial fibrillation (AF). However, it is unclear whether this is the consequence of altered haemodynamics or a direct aldosterone effect. It was the aim of the study to demonstrate load-independent effects of aldosterone on atrial structure and electrophysiology. METHODS: Osmotic mini-pumps delivering 1.5 µg/h aldosterone were implanted subcutaneously in rats (Aldo). Rats without aldosterone treatment served as controls. After 8 weeks, surface electrocardiogram, the inducibility of AF, and atrial pressures were recorded in vivo. In isolated working hearts, left ventricular function was measured, and conduction in the right atrium (RA) and the left atrium (LA) was mapped epicardially. The atrial effective refractory period (AERP) was determined. Atrial tissue was analysed histologically. RESULTS: Neither systolic nor diastolic ventricular function nor atrial pressures were altered in Aldo rats. All Aldo (11/11) showed inducible atrial arrhythmias vs. two of nine controls (P = 0.03). In Aldo, the P-wave duration and the total RA activation time were longer. Prolongation of local conduction times occurred more often in Aldo, whereas the AERP did not differ between both groups. In Aldo, atrial fibroblasts and interstitial collagen were increased, active matrix metalloproteinase 13 was reduced, and atrial myocytes were hypertrophied. The connexin 43 content was unaltered. CONCLUSIONS: Aldosterone causes a substrate for atrial arrhythmias characterized by atrial fibrosis, myocyte hypertrophy, and conduction disturbances. The described model imputes atrial proarrhythmia directly to aldosterone, since ventricular haemodynamics appeared unaltered in this model. This mechanism may have therapeutical impact for primary and secondary prevention of AF.

Electropathological substrate of longstanding persistent atrial fibrillation in patients with structural heart disease: epicardial breakthrough.

BACKGROUND: During persistent atrial fibrillation (AF), waves with a focal spread of activation are frequently observed. The origin of these waves and their relevance for the persistence of AF are unknown. METHODS AND RESULTS: In 24 patients with longstanding persistent AF and structural heart disease, high-density mapping of the right and left atria was performed during cardiac surgery. In a reference group of 25 patients, AF was induced by rapid pacing. For data analysis, a mapping algorithm was developed that separated the fibrillatory process into its individual wavelets and identified waves with a focal origin. During persistent AF, the incidence of focal fibrillation waves in the right atrium was almost 4-fold higher than during acute AF (median, 0.46 versus 0.12 per cycle per 1 cm² (25th to 75th percentile, 0.40 to 0.77 and 0.01 to 0.27; P<0.0001). They were widely distributed over both atria and were recorded at 46 ± 18 of all electrodes. A large majority (90.5) occurred as single events. Repetitive focal activity (>3) happened in only 0.8. The coupling interval was not more than 11 ms shorter than the average AF cycle length (P=0.04), and they were not preceded by a long interval. Unipolar electrograms at the site of origin showed small but clear R waves. These data favor epicardial breakthrough rather than a cellular focal mechanism as the underlying mechanism. Often, conduction from a site of epicardial breakthrough was blocked in 1 or more directions. This generated separate multiple wave fronts propagating in different directions over the epicardium. CONCLUSIONS: Focal fibrillation waves are due to epicardial breakthrough of waves propagating in deeper layers of the atrial wall. In patients with longstanding AF, the frequency of epicardial breakthroughs was 4 times higher than during acute AF. Because they provide a constant source of independent fibrillation waves originating over the entire epicardial surface, they offer an adequate explanation for the high persistence of AF in patients with structural heart disease.

Electropathological substrate of long-standing persistent atrial fibrillation in patients with structural heart disease: longitudinal dissociation.

BACKGROUND: The electropathological substrate of persistent atrial fibrillation (AF) in humans is largely unknown. The aim of this study was to compare the spatiotemporal characteristics of the fibrillatory process in patients with normal sinus rhythm and long-standing persistent AF. METHODS AND RESULTS: During cardiac surgery, epicardial mapping (244 electrodes) of the right atrium (RA), the left lateral wall (LA), and the posterior left atrium (PV) was performed in 24 patients with long-standing persistent AF. Twenty-five patients with normal sinus rhythm, in whom AF was induced by rapid pacing, served as a reference group. A mapping algorithm was developed that separated the complex fibrillation process into its individual elements (wave mapping). Parameters used to characterize the substrate of AF were (1) the total length of interwave conduction block, (2) the number of fibrillation waves, and (3) the ratio of block to collision of fibrillation waves (dissociation index). In 4403 maps of persistent AF, no evidence for the presence of stable foci or rotors was found. Instead, many narrow wavelets propagated simultaneously through the atrial wall. The lateral boundaries of these waves were formed by lines of interwave conduction block, predominantly oriented parallel to the atrial musculature. Lines of block were not fixed but continuously changed on a beat-to-beat basis. In patients with persistent AF, the total length of block in the RA was more than 6-fold higher than during acute AF (median, 21.1 versus 3.4 mm/cm(2); P<0.0001). The highest degree of interwave conduction block was found in the PV area (33.0 mm/cm(2)). The number of fibrillation waves during persistent AF was 4.5/cm(2) compared with 2.3 during acute AF, and the dissociation index was 7.3 versus 1.5 (P<0.0001). The interindividual variation of these parameters among patients was high. CONCLUSIONS: Electric dissociation of neighboring atrial muscle bundles is a key element in the development of the substrate of human AF. The degree of the pathological changes can be measured on an individual basis by electrophysiological parameters in the spatial domain.

Role of progressive widening of the temporal excitable gap for perpetuation of atrial fibrillation in the goat.

BACKGROUND: Previous studies suggest that a short temporal excitable gap exists between the fibrillation waves during atrial fibrillation (AF). The aim of this study was to investigate the role of that gap in the development of sustained AF in goats. METHODS AND RESULTS: Eight female goats were instrumented with left atrium (LA) electrodes, and sustained AF (>24 h) was induced by intermittent rapid atrial pacing for 9.3+/-4.6 days. In the process of sustained AF development, the atrial effective refractory period (AERP), refractory period during AF (RP(AF)), mean AF cycle length (AFCL), temporal excitable gap during AF (EG(AF) = AFCL - RP(AF)) and degree of fractionation of fibrillation electrograms at LA were studied. When the induced AF lasted for 3-10 min, AFCL, RP(AF) and EG(AF) were 98.3+/-11.0 ms, 90.5+/-13.2 ms and 7.8+/-2.4 ms, respectively. During sustained AF, the values were 84.9+/-5.2 ms, 63.0+/-4.8 ms and 21.9+/-3.5 ms, respectively (P<0.05). Percentage of single potentials was 94.2+/-3.9% and 75.6+/-5.5%, respectively (P<0.05). CONCLUSIONS: In this model progressive shortening of atrial refractoriness and widening of the temporal excitable gap induced by electrical remodeling created an electrophysiologic substrate for the perpetuation of AF.

Analysis of fractionated atrial fibrillation electrograms by wavelet decomposition.

This study introduces the use of wavelet decomposition of unipolar fibrillation electrograms for the automatic detection of local activation times during complex atrial fibrillation (AF). The purpose of this study was to evaluate this technique in patients with structural heart disease and longstanding persistent AF. In 46 patients undergoing cardiac surgery, unipolar fibrillation electrograms were recorded from the right atrium, using a mapping array of 244 electrodes. In 25 patients with normal sinus rhythm, AF was induced by rapid pacing, whereas 21 patients were in persistent AF. In patients with longstanding AF, the atrial electrograms showed a high degree of fractionation. In each patient, 12 s of AF were analyzed by wavelet transformation (15 scales). The finest scales (1-7) were used to reconstruct a "local" fibrillation electrogram, whereas with the coarse scales (9-15), a far-field signal was generated. With these local and far-field electrograms, the "primary" fibrillation potentials, due to wave propagation underneath the electrode, could be distinguished from double potentials and multiple components generated by remote wavefronts. Wavelet transformation resulted in AF histograms with a closely gaussian distribution and the automatically generated activation maps showed a good resemblance with fibrillation maps obtained by laborious manual editing. A special chaining algorithm was developed to detect multiple components in fractionated electrograms. The degree of fractionation showed a positive correlation with the complexity of fibrillation, thus providing an objective quantification of the degree of electrical dissociation of the atria. Wavelet transformation can be a useful technique to detect the primary potentials and quantify the degree of fractionation of fibrillation electrograms. This could enable real-time mapping of complex cases of human AF and classification of the underlying electropathological substrate.

Progression from paroxysmal to persistent atrial fibrillation clinical correlates and prognosis.

OBJECTIVES: We investigated clinical correlates of atrial fibrillation (AF) progression and evaluated the prognosis of patients demonstrating AF progression in a large population. BACKGROUND: Progression of paroxysmal AF to more sustained forms is frequently seen. However, not all patients will progress to persistent AF. METHODS: We included 1,219 patients with paroxysmal AF who participated in the Euro Heart Survey on AF and had a known rhythm status at follow-up. Patients who experienced AF progression after 1 year of follow-up were identified. RESULTS: Progression of AF occurred in 178 (15%) patients. Multivariate analysis showed that heart failure, age, previous transient ischemic attack or stroke, chronic obstructive pulmonary disease, and hypertension were the only independent predictors of AF progression. Using the regression coefficient as a benchmark, we calculated the HATCH score. Nearly 50% of the patients with a HATCH score >5 progressed to persistent AF compared with only 6% of the patients with a HATCH score of 0. During follow-up, patients with AF progression were more often admitted to the hospital and had more major adverse cardiovascular events. CONCLUSIONS: A substantial number of patients progress to sustained AF within 1 year. The clinical outcome of these patients regarding hospital admissions and major adverse cardiovascular events was worse compared with patients demonstrating no AF progression. Factors known to cause atrial structural remodeling (age and underlying heart disease) were independent predictors of AF progression. The HATCH score may help to identify patients who are likely to progress to sustained forms of AF in the near future.