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Little is known about the electrophysiological properties of the atrium predisposing to paroxysmal atrial fibrillation (AF), especially in patients without structural heart disease. This study was conducted to analyze intraatrial conduction, atrial refractoriness, and arrhythmia inducibility in patients with lone paroxysmal AF. An electrophysiological study was performed in 24 patients with a documented history of lone paroxysmal AF but in sinus rhythm at the time of the electrophysiological study. Twelve patients without any history of atrial arrhythmias served as controls. The patients with lone paroxysmal AF showed a significant prolonged local conduction time S1A1 (70 +/- 21 ms vs 36 +/- 12 ms, P0.0001), a lack of rate adaptation of the functional refractory period (FRP changes/cycle length changes10% in 15 of 24 patients with lone paroxysmal AF vs 1/12 controls, P = 0.002) and a higher incidence of inducible AF with only one extrastimulus (13/24 vs 0/12, P = 0.0014). The total P wave duration in the surface ECG (89 +/- 14 ms vs 83 +/- 8 ms, P = 0.15), the intraatrial conduction time (36 +/- 14 ms vs 28 +/- 8 ms, P = 0.07), the presence of a fragmented atrial electrogram (16/24 vs 7/12, P = 0.62), the absolute value of the effective refractory period (204 +/- 28 ms vs 212 +/- 23 ms, P = 0.42), and the vulnerability index (3.0 +/- 1.5 vs 3.6 +/- 1.5, P = 0.26) were not statistically different between the two groups. The presence of a prolonged (50 ms) S1A1 and/or the presence of a lack of rate adaptation of the FRP and/or the presence of inducible AF identified patients with spontaneous lone paroxysmal AF with a sensitivity of 96%, a specificity of 67%, a positive predictive value of 85%, and a negative predictive value of 89%. In patients with lone paroxysmal AF, the electrophysiological study using conventional techniques allows not only to detect AF inducibility using a nonaggressive protocol, but also to reveal several electrophysiological abnormalities related to the atrial substrate itself. This atrial vulnerability may explain the high incidence of recurrences in patients with lone paroxysmal AF.

The term atrial fibrillation encompasses several types of tachyarrhythmias whose common denominator is a rapid generation of atrial impulses that, with greater or lesser regularity, are conducted to the rest of the atrial myocardium, resulting in irregular ventricular responses due to variable degrees of penetration of the atrioventricular (AV) node. Advances in the treatment of atrial fibrillation using catheter ablation techniques have been achieved despite the lack of a clear idea of the different etiological and pathogenic types of this arrhythmia. Until recently, in epidemiological and even pharmacological studies, patients with atrial flutter and fibrillation were grouped under a single umbrella. Fortunately, we now know that it is necessary to separate the two. Flutter is the most common type of tachycardia secondary to atrial macroreentry, and the variety most frequently detected can be cured by means of ablation of the lower right atrial isthmus, also referred to as the cavotricuspid isthmus. Certain types of atrial fibrillation can be cured or improved by means of catheter ablation techniques; however, to continue progressing, we will have to contemplate the horizon of atrial fibrillation in the absence of past prejudices. In this respect, it would be interesting to reflect on certain considerations inspired by the article published in this issue of REVISTA ESPANOLA DE CARDIOLOGIA by Planas et al,1 aimed at determining the frequency and the factors involved in recurrences following a first episode of primary atrial fibrillation.

The aim of this study is to evaluate the mid-term clinical and functional outcomes of maze surgery in symptomatic refractory lone atrial fibrillation (AF) patients. Between March 2008 and January 2013, 39 highly symptomatic patients [mean age 51 +/- 10 (mean +/- standard deviation); 95% CI, European Heart Rhythm Association class III-IV] underwent maze surgery for lone AF. Biatrial ablations were performed with bipolar radiofrequency and cryoenergy, according to a maze III lesion set (modified by omitting the intercaval line in 5 of 39 patients). Mean ejection fraction was 51 +/- 9% (range 17-60), < 45% in 10 patients (26%). Seventeen of 39 patients (44%) had persistent, 22 of 39 patients (56%) long-standing persistent AF, and 35 of 39 patients (90%) had previous transvenous ablations (median = 2; range 0-8). No patient had concomitant structural heart disease. A minimally invasive approach was adopted in 22 patients (56%). Major complications were 1 mediastinitis, 1 re-exploration for bleeding and 2 pacemaker (5%) implantation. At a mean follow-up of 29.4 +/- 14.2 months, freedom from arrhythmias was 92 and 93% at 24 and 36 months, respectively. Freedom without antiarrhythmic drugs was 75 and 85% at 24 and 36 months, respectively. Ejection fraction normalized in all cases, from 51.3 +/- 9% to 61.1 +/- 3% (P < 0.001) overall, and from 37.0 +/- 10% to 60.3 +/- 3% (P < 0.001) when a parts per thousand currency sign45% preoperatively. AF-related symptoms score decreased to class I in 36 patients (93%). No early or late stroke occurred. Within a dedicated AF centre, maze surgery grants excellent outcomes, with symptoms relief and negligible risk. It provides a complete reversal of arrhythmia-related myocardial dysfunction and is therefore a convenient alternative to His bundle ablation and lifelong pacemaker dependency in symptomatic refractory patients.

Transforming growth factor-β1 (TGF-β1) is an important mediator of atrial fibrosis and atrial fibrillation (AF). But the involved genetic mechanism is unknown. Herein, the TGF-β1 C-509T polymorphism (rs1800469) was genotyped in a case-control study of 840 patients and 845 controls in Chinese population to explore the association between the polymorphism and susceptibility and prognosis of lone AF. As a result, the CT and/or TT genotypes had an increased lone AF risk [adjusted odds ratio (OR) = 1.50 for CT, OR = 3.72 for TT, and OR = 2.15 for CT/TT], compared with the TGF-β1CC genotype. Moreover, patients carrying CT/TT genotypes showed a higher possibility of AF recurrence after catheter ablation, compared with patients carrying CC genotype. In a genotype-phenotype correlation analysis using 24 normal left atrial appendage samples, increasing gradients of atrial TGF-β1 expression levels positively correlated with atrial collagen volume fraction were identified in samples with CC, CT and TT genotypes. The in vitro luciferase assays also showed a higher luciferase activity of the -509T allele than that of the -509C allele. In conclusion, the TGF-β1 C-509T polymorphism is involved in the etiology of lone AF and thus may be a marker for genetic susceptibility to lone AF and predicting prognosis after catheter ablation in Chinese populations. Therefore, we provide new information about treatment strategies and our understanding of TGF-β1 in AF. © 2014 Cao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

BACKGROUND The extent to which atrial myocardium is remodeled in patients with persistent lone atrial fibrillation (LAF) is largely unknown. OBJECTIVE The purpose of this study was to perform a clinicopathologic investigation in patients with persistent LAF. METHODS We characterized structural and molecular remodeling in atrial biopsies from 19 patients (17 males, mean age 49 years) with persistent (> 7 days; n = 8) or long-lasting persistent (> 1 year; n = 11) LAF who underwent surgical ablation. Atrial tissue from 15 autopsy samples without clinicopathologic evidence of heart disease served as controls. RESULTS Morphometric analysis showed cardiomyocyte hypertrophy and greater amounts of myolytic damage and interstitial fibrosis in persistent LAF patients compared to controls (P

BackgroundSystemic inflammation is accepted as one of the pathophysiological mechanisms of atrial fibrillation (AF). The role of inflammation has been shown previously. Interleukin (IL) system is the main modulator of the inflammatory responses and genetic polymorphisms of IL-1 cluster genes are associated with increased risk for inflammatory diseases. ObjectivesTo investigate the association between polymorphisms of IL-1 cluster genes and lone AF. Subjects and MethodsDNA samples were collected from 70 proven lone AF patients and 70 healthy subjects. Genomic DNA was typed for the variable number of the tandem repeat (VNTR) IL-1 receptor antagonist (RN) gene polymorphism, IL-1B -511 C > T(rs16944) promoter polymorphism, and +3953 C > T(rs1143634) polymorphism in exon 5 by polymerase chain reaction. ResultsIn lone AF group the frequency of IL-1RN2/2 and IL-1RN1/2 genotypes were higher than in the control group (7.2% vs 4.3% and 48.5% vs 22.8%, respectively; (2) = 14.1; P = 0.028). The frequency of allele 2 was significantly higher in the lone AF group (32.1% vs 15.7%; (2) = 10.7; P = 0.005). Allele and genotype distribution of IL-1B -511 C > T and +3953 C > T polymorphisms were not statistically different between the groups. C-reactive protein (CRP) levels were higher in lone AF patients compared to the control group (median = 1.25, interquartile range [IQR] = 0.85 vs median = 1.08, IQR 0.46 mg/L, respectively; P = 0.02). In multivariate regression analysis, presence of allele 2 of IL-1 VNTR polymorphism and elevated plasma high-sensitive-CRP levels were the independent predictors of lone AF. ConclusionPresence of allele 2 of VNTR polymorphism of IL-1RN gene may cause increased risk for lone AF probably due to the inadequate limitation of inflammatory reactions.

Pectus excavatum is a skeletal abnormality that may have cardiac manifestations.To determine whether pectus excavatum is associated with lone atrial fibrillation (AF).The pectus severity index (PSI) is the ratio of the lateral diameter of the chest to the distance between the sternum and the spine on computed tomography scan. A normal PSI is ≤2.5 whereas patients with severe pectus excavatum have a PSI3.25. We calculated the PSI of 220 consecutive patients with AF who underwent radiofrequency catheter ablation from September 2008 to 2012 and compared this to the PSI of 225 controls without a history of AF undergoing chest computed tomography.Mean PSI was higher in patients with lone AF (2.72 ± 0.07) compared to patients with nonlone AF (2.25 ± 0.03) or controls (2.26 ± 0.03) (P.001). The likelihood of mild, moderate, or severe pectus excavatum was higher in patients with lone AF compared to patients with nonlone AF and controls (P.001). Patients with lone AF were more than 5 times as likely to have severe pectus excavatum compared to patients with nonlone AF or controls (P.001) even after adjustment for potential confounders.Nearly two-thirds of the patients with lone AF have at least mild pectus excavatum and 17% have severe pectus, which is significantly higher than in patients with nonlone AF or controls. This association suggests a potential genetic or mechanical abnormality may be common to the 2 disorders. Our study may provide insight into the pathogenesis of lone AF.

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Background: Our main purpose in this study is to compare atrial (inter-atrial, intra-leftatrial, intra-right atrial) electromechanical delays of patients with lone atrial fibrillation (LAF) with healthy individuals and examine the relationship of annual LAF attack frequency. Methods: 32 entirely healthy individuals and 32 patients who have presented with tachycardia and complying with LAF criteria have been included in the study. The time passing from the beginning of the P wave on electrocardiography to the A’ wave on tissue Doppler trace was accepted as the atrial conduction time (PA’). The PA’ time difference between the mitral annulus of left ventricle (ML) and the tricuspid annulus of right ventricle (TL) was defined as inter-atrial electromechanical delay (IA-EMD), the PA’ time difference between the ML and septal mitral annulus (MS) as intra-left electromechanical delay (ILeft-EMD), the PA’ time difference between MS and the TL as intra-right electromechanical delay (IRight-EMD). Results: ILeft-EMD (21.8 ± 9.1 vs. 14.1 ± 4.9, p < 0.001), IRight-EMD (9.3 ± 6.8 vs. 5.9 ± 4.9, p = 0.03) and IA-EMD times (24.7 ± 11.2 vs. 11.9 ± 7.1, p < 0.001) were significantly longer in LAF patients. In multivariate regression analysis, using a model including age, gender and left atrium (LA) volumes, ILeft-EMD times (OR 1.14, 95% CI 1.03–1.27,p = 0.012), IA-EMD times (OR 1.12, 95% CI 1.03–1.23, p = 0.007) and LA volumes (OR 1.18, 95% CI 1.05–1.32, p = 0.005) were independent predictors of LAF. In LAF group, the frequency of AF episodes was significantly correlated with ILeft-EMD (r = 0.90, p < 0.001) and IA-EMD times (r = 0.36, p < 0.004), whereas, IRight-EMD times and LA volumes were not correlated with recurrence rates. Conclusions: ILeft-EMD and IA-EMD may increase in the early stages of atrial fibrillation even without the left atrial dilation and may be more valuable than left atrial area and volume in predicting atrial fibrillation.

The limitations of current therapies for atrial fibrillation are forcing a rethinking of how they should be used. Questions are being raised about the use of antiarrhythmic drugs, and new nonpharmacologic procedures are promising alternatives. Most patients with atrial fibrillation still require warfarin therapy, but some low-risk patients can forego it. Sinus rhythm spontaneously returns within the first 24 hours in almost half of cases of new atrial fibrillation. Patients with hemodynamic instability due to new-onset atrial fibrillation should proceed directly to electrical cardioversion. Warfarin therapy to maintain an International Normalized Ratio (INR) of 2.0 to 3.0 is currently recommended for all patients with atrial fibrillation with no contraindications to it, except for patients younger than 60 years with lone atrial fibrillation, in whom the risk of stroke is low. Certain antiarrhythmic drugs should be avoided in patients with congestive heart failure, in whom the risks may exceed the benefits. The maze procedure is emerging as an option to restore and maintain sinus rhythm. Radiofrequency atrioventricular node ablation and modification hold promise as options to control the ventricular rate without drugs.

With interest we read the Letter-to-the-Editor by Suwalski regarding our short communication in the Thoracic and Cardiovascular Surgeon and would like to take the opportunity to response to some of the issues raised. First of all, we would like to refer to our article and our response to the letter on this subject by van Putte et al. Once again, not all three patients had their TTMAZE surgery in our center. This is clearly described in our short communication. Second, our center has a proven track record, extending over 15 years, in performing surgery for lone atrial fibrillation and concomitant surgery for atrial fibrillation by a dedicated surgeon. In our open procedures, we have never encountered this complication. We also like to state that the TTMAZE procedures were performed after a formal training and introduction program and were applied according to the instructions given by AtriCure. The difficulty with this complication is the low rate of occurrence and the relatively long time frame between initial surgery and the occurrence of the complication. In this light, we advocate that our communication is seen as a matter of caution. There is a small potential of a highly devastating, even lethal, complication with this procedure. We are convinced that these fistulas are not a single-center problem. The exact mechanism of this complication remains unclear. As we described, the lesion is seen centrally in the posterior wall of left atrium, away from the ablation lines.[3] The fistula needs several weeks (6–8) to develop and to cause septicemia and air embolism. This, in our view, seems to exclude a lesion caused by wrongly applied pressure or manipulation of tissue. Moreover, relatives of all the three patients reported well-being of patients until a day or even hours before collapse or neurological impairment. To conclude, we agree that TTMAZE shows good results in treating lone atrial fibrillation. We also agree that the track record of TTMAZE is excellent in high-volume centres.[4] We do, however, warn about the potential complication of an atrio-esophageal fistula and emphasize the need for stringent follow-up of all patients and further research into the pathogenesis of this complication.

[8] Kirchhof P, Kahr PC, Kaese S, et al. PITX2c is expressed in the adult left atrium, and reducing Pitx2c expression promotes atrial fibrillation inducibility and complex changes in gene expression. Circ Cardiovasc Genet 2011;4:123–33. [9] Mommersteeg MT, Brown NA, Prall OW, et al. Pitx2c and Nkx2-5 are required for the formation and identity of the pulmonary myocardium. Circ Res 2007;101:902–9. [10] Chinchilla A, Daimi H, Lozano-Velasco E, et al. PITX2 insufficiency leads to atrial electrical and structural remodeling linked to arrhythmogenesis. Circ Cardiovasc Genet 2011;4:269–79. [11] Posch MG, Boldt LH, Polotzki M, et al. Mutations in the cardiac transcription factor GATA4 in patients with lone atrial fibrillation. Eur J Med Genet 2010;53:201–3. [12] Yang YQ, Wang XH, Tan HW, Jiang WF, Fang WY, Liu X. Prevalence and spectrum of GATA6 mutations associated with familial atrial fibrillation. Int J Cardiol 2012;155:494–6. [13] Yang YQ,Wang J, Wang XH, et al. Mutational spectrum of the GATA5 gene associated with familial atrial fibrillation. Int J Cardiol 2012;157:305–7.

The maze procedure is a therapeutic option for selected patients with standalone atrial fibrillation. Advances in ablation technology have made feasible a range of minimally invasive approaches, avoiding some of the morbidity and technical complexities of the classic maze procedure. Further, combining surgical and transvenous techniques allows a staged approach. We describe the technical aspects of the surgical portion of a staged hybrid approach developed by our group, using a bilateral thoracoscopic-assisted mini-thoracotomy approach with bipolar radiofrequency ablation. In our practice, we have found the minimally invasive bilateral thoracoscopic maze to be a safe and efficacious part of a staged strategy for the treatment of lone atrial fibrillation.

The aim of this study was to investigate the effect of statin therapy on arrhythmia recurrence in patients with lone atrial fibrillation (AF). From July 1998 to December 1999, 62 patients with lone persistent AF lasting/=3 months underwent successful external cardioversion. After a mean follow-up of 44 months, 85% had recurrence of AF. The use of statins was associated with a significant decrease in the risk of arrhythmia recurrence after successful cardioversion of AF. The result of this retrospective study demonstrates that the use of statins in patients with lone AF was associated with a significant decrease in the risk of arrhythmia recurrence after successful cardioversion.

Aims Genetic factors may be important in the development of atrial fibrillation (AF) in the young. KCNA5 encodes the potassium channel α-subunit KV1.5, which underlies the voltage-gated atrial-specific potassium current I Kur. KCNAB2 encodes KVβ2, a β-subunit of KV1.5, which increases I Kur. Three studies have identified loss-of-function mutations in KCNA5 in patients with idiopathic AF. We hypothesized that early-onset lone AF is associated with high prevalence of genetic variants in KCNA5 and KCNAB2 . Methods and results The coding sequences of KCNA5 and KCNAB2 were sequenced in 307 patients with mean age of 33 years at the onset of lone AF, and in 216 healthy controls. We identified six novel non-synonymous mutations [E48G, Y155C, A305T (twice), D322H, D469E, and P488S] in KCNA5 in seven patients. None were present in controls. We identified a significantly higher frequency of rare deleterious variants in KCNA5 in the patients than in controls. The mutations were analysed with confocal microscopy and whole-cell patch-clamp techniques. The mutant proteins Y155C, D469E, and P488S displayed decreased surface expression and loss-of-function in patch-clamp studies, whereas E48G, A305T, and D322H showed preserved surface expression and gain-of-function for KV1.5. Conclusion This study is the first to present gain-of-function mutations in KCNA5 in patients with early-onset lone AF. We identified three gain-of-function and three loss-of-function mutations. We report a high prevalence of variants in KCNA5 in these patients. This supports the hypothesis that both increased and decreased potassium currents enhance AF susceptibility.

Dr. James Cox devised the maze procedure as a radical intervention for lone atrial fibrillation (AF) based on the multiple reentry theory. Dr. Micheal Haissaguerre discovered ectopic foci from the pulmonary veins were the trigger for paroxysmal AF. We demonstrated the efficacy of the pulmonary vein box isolation procedure for chronic AF. Dr. Koonlfawee Nademanee reported the complex fractionated atrial electrogram (CFAE) procedure to eliminate the substrate of chronic AF, which is distributed around the pulmonary veins. The complete isolation of all pulmonary veins is essential for the elimination of AF.

Atrial Remodeling and Lone Atrial Fibrillation. Background: We sought to investigate the role of anatomic remodeling of the atria and pulmonary veins (PVs) in the progression of lone atrial fibrillation (AF) using dual-source computed tomography (DSCT). Methods and Results: From 1,308 consecutive patients referred for an index ablation procedure for AF, we prospectively enrolled 29 consecutive patients with recently developed (

Lone atrial fibrillation (AFIB), or AFIB occurring in a patient with a structurally and functionally normal heart, is rare in children and adolescents. There are several reports suggesting that other forms of SVT (ie AVNRT, AVRT, or EAT) could trigger AFIB in these patients. We sought to determine

AIM: To investigate the prevalence of clinically unrecognized mitral regurgitation (MR) in lone atrial fibrillation (AF). METHODS: We studied the prevalence and severity of MR by transesophageal echocardiography (TEE) in patients with “lone” AF as compared to a matched cohort of patients in normal sinus rhythm (NSR) undergoing TEE for other indications besides recognized valvular heart disease. RESULTS: A total of 157 subjects (57 in the AF group and 100 in the NSR group) with structurally normal cardiac valves were included in the study. In the AF group, moderate MR or more was noted in 66% of the patients, mild MR in 18%, trace or no MR in 16%. In the control group, moderate MR was noted in 6% of patients, mild MR 31%, trace or no MR in 63 % of patients. Moderate MR or greater was significantly more prevalent in the AF group compared to the NSR group (66% vs 6%, P < 0.0001). CONCLUSION: Clinically unrecognized moderate MR is prevalent in “lone” AF -either as an etiologic factor leading to “lone” AF or developing after onset of AF.

慢性孤立性心房細動例の心拍数調整にジギタリス (D) , β遮断薬 (B) , Ca拮抗薬 (Oa) , およびそれらの併用投与を行ない, ホルター心電図, 運動負荷心電図上の諸パラメーターの変化を比較し次の結果を得た.(1) Dはmax HR, 運動時HR, mean HRを有意に減少したが, min HR, 夜間HRも同時に減少させ, max RRを延長した.(2) Bはmax HR, 運動時HR, mean HRを減少させたが, min HRはあまり減少させずmax RRの延長も比較的少なかった.(3) Caは量的に不足だったが, 傾向としてはBと同様と思われた.(4) 2剤併用により強力なmax HR, mean HRの減少効果が得られたが, 徐拍化も著しく注意が必要と思われた.(5) SDーRR, CVについてはD, B, Caとも著変を生じなかった.

Atrial fibrillation (AF) is the most frequent supraventricular arrhythmia, and its therapy is still unsatisfactory. Different theories have been proposed to explain its mechanism. Nowadays it seems well accepted that both focal and re-entrant mechanisms are involved, playing a different role in the

An intact male Pointer aged 9 year was found to have atrial fibrillation (AF). Thoracic radiography and echocardiography as well as routine blood work revealed no cardiac disease. Thus, the dog was diagnosed as lone AF. The arrhythmia disappeared 6 hr after the initiation of the supportive therapy, and relapse was not observed.

As the most common cardiac arrhythmia, atrial fibrillation has been the subject of investigation for the past few decades. During this time, surgical treatment for patients with this condition has evolved significantly. After the history of surgical therapy for atrial fibrillation is discussed, this article examines current surgical therapeutic options, including the most recent progress on energy sources, concomitant surgical ablation, and minimally invasive surgical ablation for lone atrial fibrillation. The article also highlights the hybrid approaches that are currently being researched.

To the Editor: In the June issue of Circulation: Cardiovascular Genetics , Kattygnarath and coworkers report MOG1 as a new susceptibility gene for Brugada syndrome (BrS).1 A missense mutation p.E83D was identified in a female patient with aborted sudden cardiac death but not in 281 control subjects. This very interesting finding adds to our understanding of BrS and the (patho-) physiological role of macromolecular complexes underlying the sodium current INa in the heart. Yet, we would like to raise some concerns about this new player in the genetics of BrS. Very recently, we have screened MOG1 in cohorts of BrS and early-onset lone atrial fibrillation.2 In 4 of 209 lone atrial fibrillation cases, we identified a nonsense variation c.181G>T (p. E61X), resulting in premature stop codon …

We want to answer the letter Olesen et al addressed to Circulation: Cardiovascular Genetics after the publication of our report on MOG1 as a new susceptibility gene for Brugada syndrome (BrS). Olesen et al1 screened MOG1 in 23 patients with BrS and in 197 patients with early-onset lone atrial fibrillation, and they identified the nonsense variation c.181G>T (p.E61X) in 4 patients with atrial fibrillation, resulting in a premature stop codon that truncates the protein upstream of the region that interacts with Nav1.5. They also identified this variant in 2 of 488 healthy individuals (ie, in 0.4% of control subjects vs 1.8% of patients). As indicated by Olesen et al, we reported this nonsense variant at the American Heart Association 2009 scientific sessions,2 in an asymptomatic male patient with a type 1 BrS ECG. This variant was thought to be relevant because it had not been found in 100 control individuals. We later found it in 3 other BrS probands, positive or negative for the SCN5A mutation, and in some family members; in addition, we found it in …

Background— Plasma B-type natriuretic peptide (BNP) is abnormally elevated in patients with lone atrial fibrillation (AF). The exact significance and prognostic implications of this elevation have yet to be determined. Little is known about BNP in lone AF patients undergoing arrhythmia ablation. We sought to determine the relationship between BNP levels and the risk of recurrent arrhythmia after ablation of lone AF. Methods and Results— We followed up 726 patients with lone AF undergoing first-time arrhythmia ablation. All had BNP levels measured on the day of ablation with of the point-of-care Triage Meter assay (Biosite Diagnostics, San Diego, CA). At baseline, factors associated with elevated BNP levels in multivariable linear regression analysis (with log BNP being the dependent variable) were older age (β regression coefficient for +1-year change, 0.025; P P =0.01), nonparoxysmal AF (versus paroxysmal; β, 0.52; P 2 change, 0.040; P P P P for trend across quintiles Conclusions— B-type natriuretic peptide levels correlate with AF burden (chronicity, altered hemodynamics, and anatomic remodeling) in patients with lone AF and are strong predictors of recurrent arrhythmia after ablation. Elevated BNP levels may reflect increased cardiac chamber wall stress and/or intrinsic atrial disease, thus increasing the risk of arrhythmia recurrence.

Currently, off-pump video-assisted thoracoscopic epicardial pulmonary vein isolation offers an attractive alternative to on-pump Maze procedures for surgical treatment of lone atrial fibrillation. Nevertheless, on-pump Maze procedures through a mid-sternotomy approach still play an important role in patients with lone atrial fibrillation on many occasions, especially in patients with failed percutaneous pulmonary vein alone. The aim of this article was to give a brief review of the surgical strategies for treating lone atrial fibrillation, and present the possible indications for on-pump Maze procedures through a mid-sternotomy approach. Atualmente, isolamento epicárdico da veia pulmonar com cirurgia torácica vídeo-assistida sem circulação extracorpórea oferece uma alternativa atraente para procedimento de Maze com circulação extracorpórea no tratamento cirúrgico da fibrilação atrial solitária. No entanto, procedimento de Maze com circulação extracorpórea através de uma meio-esternotomia ainda desempenha papel importante em pacientes com fibrilação atrial isolada em várias ocasiões, especialmente em pacientes com falha da veia pulmonar percutânea isoladamente. O objetivo do artigo é fazer uma breve revisão de estratégias para o tratamento cirúrgico fibrilação atrial isolado e apresentar as possíveis indicações de procedimento de Maze com extracorpórea, através de uma abordagem meio-esternotomia.

Atrial fibrillation is the most common sustained rhythm disturbance. Thromboembolic events related to atrial fibrillation result in significant morbidity, mortality and increases in the cost of healthcare. Anticoagulants are pivotal agents for the prevention and treatment of thromboembolic disorders. The latest American College of Cardiology/American Heart Association guidelines recommend antithrombotic therapy to prevent thromboembolism for all patients with atrial fibrillation, except those with lone atrial fibrillation or contraindications. Vitamin K antagonists were first synthesized in 1948 and for the past six decades they have been the only agents used for long-term oral anticoagulant therapy. Although these drugs are effective, they have numerous limitations, which have led to the development of newer anticoagulant therapies. The emerging oral anticoagulant agents are target selective. They have predictable pharmacokinetic and pharmacodynamic parameters and do not require routine monitoring. They are not associated with significant food and drug interactions, and can be administered in simple fixed daily or twice daily doses. This article reviews the current literature on various targets for anticoagulant therapy and newer oral anticoagulants for atrial fibrillation.

Aims Patients with a history of atrial fibrillation (AF) have previously been shown to have altered atrial conduction, as seen non-invasively using signal-averaged P-wave analysis. However, little is known about the P-wave morphology in patients in the early phases of AF with structurally normal hearts. Methods and results Thirty-six patients with lone AF were included before the age of 40 years (34 ± 4 years, 34 men) and compared with age- and gender-matched control subjects. Standard 12-lead electrocardiogram (ECG) was recorded for at least 10 s. P-wave morphology and duration were estimated using signal-averaged P-wave analysis. Echocardiography was performed in association with the ECG recording. Heart rate (67 ± 13 vs. 65 ± 7 b.p.m., P = 0.800) and PQ-interval (163 ± 16 vs. 164 ± 23 ms, P = 0.629) were similar in AF cases and controls, as was P-wave duration (136 ± 13 vs. 129 ± 13 ms, P = 0.107). The distribution of P-wave morphology differed between the AF cases and controls [33/58/0/8 vs. 75/25/0/0% (Type 1/Type 2/Type 3/atypical), P = 0.001], with a larger proportion of patients with AF exhibiting signs of impaired interatrial conduction. Conclusion A significant difference in P-wave morphology distribution was seen between patients with early-onset, lone paroxysmal AF and age- and gender-matched healthy control subjects. This finding indicates that alterations in atrial electrophysiology are common in the early stage of the arrhythmia, and since it occurs in young patients without co-morbidity may well be the cause rather than the consequence of AF. (Less)

Aims A prothrombotic state with elevated levels of soluble P-selectin (sP-sel), fibrinogen, von Willebrand factor (vWf), and other haemostatic indices has been reported in some patients with atrial fibrillation (AF). Whether these changes are due to AF itself or coexistent cardiovascular diseases remains a matter of debate. Therefore, in the present study, the differences in plasma levels of sP-sel, fibrinogen, and vWf between patients with idiopathic/lone AF and sex-, age-, and risk factor-matched controls were investigated to determine whether AF itself might be associated with a hypercoagulable state. Methods and results Ninety consecutive patients (63 males, 54.1 ± 10.1 years) with idiopathic AF were studied, 60 (43 males, 48.8 ± 7.5 years) of whom were diagnosed as lone AF. Plasma sP-sel and vWf were measured by enzyme-linked immunosorbent assay. Plasma fibrinogen was measured by chromometry. These indices in AF patients were compared with those in sex-, age- and risk factor-matched controls. Compared with the controls, patients with idiopathic AF had higher levels of sP-sel (AF vs. control: 33.4 ± 7.4 vs. 29.2 ± 6.5 ng/mL, P < 0.001) and fibrinogen (AF vs. control: 3.3 ± 0.9 vs. 3.0 ± 0.6 g/L, P = 0.02), but not vWf, whether with the adjustment of covariates or not. As for those

Methods: 174 patients with AF were included in the original analysis. 25 of these patients met criteria for Lone AF as deined by absence of structural heart disease based on history, physical examination and imaging tests including chest x-ray and echocardiography, with no history of coronary artery disease, diabetes, hypertension, and hyperthyroidism. Patients underwent DE-MRI and placed in 1 of 3 categories; Stage 1 structural remodeling (SRM) ( 35%).

In the developed world between 1% and 1.5% of the population is suffering from atrial fibrillation [1]. Due to higher life expectancy, the prevalence of this disease will grow at least 3-fold in the next 50 years. Compared to many other diseases, the health and economic burden imposed by AF and AF-related morbidity is immense.

The atrial fibrillation is linked to an overmortality (x2), except in patients with lone atrial fibrillation. The severity of atrial fibrillation is due to the risk of thromboembolism event, especially stroke. This risk is very high in presence of rhumatismal mitral valve pathology or prosthetic valve. The annual risk of thromboembolism has been evaluated and the CHADS2 score defined from 0 to 6 In function of the CHADS2 score the risk of thromboembolism event is 1.9 to 18.2%/year. Other factors of thromboembolism accident are actually evaluated such as renal insufficiency, proteinuria. The main objective of atrial fibrillation treatment is the prevention of thromboembolism event. The antivitamin K agents proved their efficiency in term of mortality and morbidity justifying to identify the patients at risk of thromboembolism event.

Background Whether and how lone atrial fibrillation (AF) is associated with functional mitral regurgitation (MR) remain unclear. Method We studied 12 lone AF patients without left ventricular (LV) dysfunction and/or dilatation, who underwent mitral valve annuloplasty for functional mitral regurgitation (MR). Ten lone AF patients without MR served as controls. Results Lone AF Patients with MR had a greater mitral valve annular area and left atrial area than those without MR. There were no differences in LV volumes or LV ejection fraction. Conclusions Therefore, we concluded that left atrial dilation and corresponding mitral annular dilation may cause MR in lone AF patients without LV dysfunction and/or dilatation.

Histologic and ultrastructural examination of atrial tissue regarding the main entities responsible of human atrial fibrillation, is reported. The pathologic changes deriving from various disorders, like degenerative, inflammatory, ischemic diseases as well as from cardiac aging and hormonal imbalance are analysed. Structural changes associated with lone atrial fibrillation and investigated by atrial biopsy are also described, as being able to provide useful information on the disease's etiology, prognosis and treatment.

Dr Mont and colleagues highlight prior papers suggesting that, in young and middle-aged adults, high-intensity endurance training is associated with higher risk of lone atrial fibrillation (AF). At first glance, such observations might appear inconsistent with our recent findings that greater habitual light-to-moderate physical activities are associated with significantly lower risk of new-onset AF in older adults.1 Several factors may explain these ostensibly divergent findings. First, AF is a common clinical manifestation of remarkably heterogeneous cardiac and noncardiac conditions, …

Lone atrial fibrillation (LAF) is atrial fibrillation without structural heart disease and is commonly observed in Standardbred horses. In certain families the disease appears to be associating as a simple autosomal trait, yet causes of equine LAF remain unknown. In humans, LAF is often caused by an inherited cardiac ion channel mutation. We hypothesized that LAF in some Standardbred horses is the result of a mutation(s) in one or more cardiac ion channel genes. A candidate gene approach was used to scan six ion channel genes for a potential LAF-causative mutation. Non-synonymous substitutions were observed in genes 'KCNH2, KCNQ1', and 'SCN5A' which did not associate with the disease in a simple Mendelian manner, but may represent risk factors. It is possible that a mutation is present in a non-coding region or a different gene, in which case a linkage analysis study may be necessary.

BACKGROUND Although the electrophysiological mechanisms underlying self-sustaining atrial fibrillation (AF) are unclear, recent studies suggest that one requirement for reentry, slow conduction, is frequently present in patients with AF. However, these observations limited to paroxysmal AF may not necessarily apply to chronic AF. Therefore, electrophysiological properties of the atrium and sinus nodal function in chronic lone AF were evaluated. METHODS AND RESULTS Electrophysiological studies were performed after electrocardioversion in 12 patients with chronic lone AF. Atrial enlargement was absent in the patients with AF. Twelve patients without atrial arrhythmias served as the control group. The patients with AF had a higher incidence of sinus nodal dysfunction, a shorter atrial effective refractory period (215 +/- 19 msec versus 238 +/- 23 msec, p less than 0.02), and a longer P wave duration than control patients (115 +/- 16 msec versus 86 +/- 16 msec, p less than 0.01). The conduction delay zone was significantly greater in patients with AF (60 +/- 12 msec) than that in the control patients (8 +/- 13 msec, p less than 0.01), and the maximal conduction delay was also greater in the study patients than those in the control group, both to the His bundle region (31 +/- 12 msec versus 10 +/- 15 msec, p less than 0.01) and to the coronary sinus (41 +/- 15 msec versus 15 +/- 11 msec, p less than 0.01). The fragmented atrial activity zone was wider in the study group (23 +/- 25 msec) than in control subjects (1.7 +/- 4 msec, p less than 0.02). Repetitive atrial firing was observed in four patients with AF but it was not seen in the control group. CONCLUSIONS These electrophysiological features, which are manifestations of the abnormal atrial electrophysiology, would favor production of atrial reentry in chronic lone AF.

In brief Prompted by President George Bush's episode of atrial fibrillation (AF) while jogging, the authors reviewed the cases of eight apparently normal, physically active men who had AF. Episode triggers included exercise and the ingestion of caffeine, alcohol, cold water, and ice cream. None of the patients had clinical hyperthyroidism. One patient had a subsequent stroke, despite anticoagulation therapy. Most of the patients were able to prevent recurrence by avoiding triggering factors. When AF recurs despite such avoidance and the use of digoxin or beta-blockers, a class 1A antiarrhythmic agent can be tried.

Animal models of atrial fibrillation have taught us about mechanisms of this common disease. A variety of animal models exist, including models of lone atrial fibrillation and models of atrial fibrillation in the setting of heart failure, aging, or pericardial inflammation. This article reviews these various models.

Background: Lone atrial fibrillation (LAF) is a common arrhythmia, but its mechanism and the aggravated factor of arrhythmia are poorly understood. Oxidative stress has been implicated in the pathogenesis of heart failure. We have previously demonstrated that the amount of 4-hydroxy-2-nonenal (HNE) modified protein, which is a major lipid peroxidation product and a cytotoxic aldehyde, causes intracellular Ca2+ overload via reactive oxygen species (ROS) formation in cardiomyocytes and leads to develop arrhythmia. Accordingly we examined the levels of HNE and major histocompatibility complex (MHC) with the disease severity in LAF patients. Method: Atrial and ventricular myocardial samples were obtained from twelve patients (11 men and 1 woman, mean 48±14 years old) by endomyocardial biopsy in 10, autopsy sample in 1 and surgical resection sample in 1. Histological assessments and immunohistochemical analysis for HNE modified protein, MHC class-I and -II antigens (grade 0 to 3) were performed and compared with LAF severity. Results: Histological assessment showed that increased number of interstitial cells (mainly activated T cells) was observed only in the atrium but not in the ventricle. Moderate to severe expression of MHC antigens (grade 2 or 3) was more observed in the atrium than the ventricle (MHC-I: seven in atrium and three in ventricle; MHC-II: ten in atrium and four in ventricle). Atrial myocarditis was detected in 6 out of 11 samples. HNE modified protein was also more observed in the atrium than that in the ventricle. In addition, more severe expression of HNE staining was observed in the samples from persistent/chronic LAF than that in paroxysmal LAF. Conclusion: These data indicates that oxidative stress plays an important role as an aggravating factor in LAF patients.

To the Editor: We read with great interest the excellent article by Dr Darbar and colleagues,1 in which the authors resequence the entire SCN5A coding region in 375 subjects with either lone atrial fibrillation (AF) or AF associated with heart disease. They draw a conclusion that mutations or rare variants in SCN5A may predispose patients with or without underlying heart disease to AF. However, although their findings represent a good starting point, it is insufficient …

OBJECTIVE The study evaluated the relationships between acute stress, lifestyle and coffee consumption, and acute lone atrial fibrillation (AF). METHODS The study group included 400 patients with mean age of 54 +/- 11 years, 205 of whom were men. They all presented with a first episode of AF. Patients underwent a series of cognitive tests to evaluate acute psychological stress (mean life acute stress score). Lifestyle and nutritional parameters (diet, alcohol and espresso coffee consumption, smoking and obesity) were investigated. An age-matched and sex-matched control group was selected and compared. RESULTS Recent stress, high intake of coffee, and obesity were associated with greater risk of AF. Acute stress induces an increase in coffee consumption and changes in lifestyle. The increase in coffee consumption was more marked in nonhabitual drinkers, leading to a higher risk of developing AF [odds ratio (OR) 4.1; 95% confidence interval (CI): 1.98-4.56; P < 0.001]. Spontaneous conversion of AF to sinus rhythm was observed in 191 patients (47%). Patients who experienced AF after an acute stress showed the highest probability of spontaneous conversion. High espresso coffee consumption (OR 0.86; 95% CI: 0.49-1.21; P < 0.01) and obesity (OR 0.88; 95% CI: 0.84-1.20; P < 0.01) were associated with a significantly greater risk of persistent AF. CONCLUSION Acute stress induced changes in lifestyle, including an increase in coffee consumption, leading to a higher risk of AF. Patients who developed AF after an acute stress showed the highest probability of spontaneous conversion. High espresso coffee consumption and obesity were associated with an increased risk of persistent AF.

The presence of lone atrial fibrillation presupposes the absence of structural heart disease, hypertension, or other known predisposing factors. However, several recent clinical and experimental data provide novel insights into the pathogenesis of lone atrial fibrillation. In addition, modern diagnostic techniques often reveal some previously unappreciated abnormalities. Therefore, the increasing recognition of potential causes and links sets the base for a more complete elucidation of its etiology in the near future. This concise review article discusses the contemporary advances in the understanding of this form of atrial fibrillation. Int J Cardiol