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Background Atrial fibrillation (AF) is a common arrhythmia characterized by uncoordinated atrial electrical activity. Lone AF occurs in the absence of traditional risk factors and is frequently observed in male endurance athletes, who face a 2‐ to 5‐fold higher risk of AF compared with healthy, moderately active males. Our understanding of how endurance exercise contributes to the pathophysiology of lone AF remains limited. This study aimed to characterize the circulating protein fluctuations during high‐intensity exercise as well as explore potential biomarkers of exercise‐associated AF. Methods and Results A prospective cohort of 12 male endurance cyclists between the ages of 40 and 65 years, 6 of whom had a history of exercise‐associated AF, were recruited to participate using a convenience sampling method. The circulating proteome was subsequently analyzed using multiplex immunoassays and aptamer‐based proteomics before, during, and after an acute high‐intensity endurance exercise bout to assess temporality and identify potential markers of AF. The endurance exercise bout resulted in significant alterations to proteins involved in immune modulation (eg, growth/differentiation factor 15), skeletal muscle metabolism (eg, α‐actinin‐2), cell death (eg, histones), and inflammation (eg, interleukin‐6). Subjects with AF differed from those without, displaying modulation of proteins previously known to have associations with incident AF (eg, C‐reactive protein, insulin‐like growth factor‐1, and angiopoietin‐2), and also with proteins having no previous association (eg, tapasin‐related protein and α2‐Heremans‐Schmid glycoprotein). Conclusions These findings provide insights into the proteomic response to acute intense exercise, provide mechanistic insights into the pathophysiology behind AF in athletes, and identify targets for future study and validation.

Purpose The aim of this study is to detect the prevalence of obstructive sleep apnea syndrome (OSAS) in patients having lone atrial fibrillation (AF). Patients and methods Fifty patients with lone AF were referred to our sleep unit from the Department of Cardiology at the University Hospital. Lone AF was defined as AF in patients without cardiac structural abnormality and less than 60 years of age. All patients were subjected to a detailed history with stress on the number and date of documented episodes of AF and how it was terminated, OSA symptoms (excessive daytime sleepiness, witnessed apnea, loud habitual snoring, and nocturnal choking), and OSA screening questionnaires. ENT and cardiac examination by a specialist was done. Full-night attended polysomnography was performed on full night. Results The median apnea–hypopnea index in the studied group was 10.8 (range, 0.4–69.4). There were 21 (42.0%) non-OSA patients, while there were 29 (58%) OSA patients. There were eight (27.6%) mild OSA patients. Moderate OSA patients were 10 (34.5%). Severe OSA patients were 11 (37.9%). Median of the frequency of AF episodes in the last 1 year was significantly higher in the OSA group than in the normal group (P=0.01). No significant difference was present between both groups as regards the number of nocturnal arrhythmias not related to respiratory events. The frequency of paroxysmal AF episodes during the last year shows a significant positive correlation with severity of OSA, desaturation index, and total arousal index. Conclusion The results of our study support our hypothesis that OSA is a risk factor for AF. We should investigate patients with lone AF for the possibility of OSA.

Purpose The aim of this study is to detect the prevalence of obstructive sleep apnea syndrome (OSAS) in patients having lone atrial fibrillation (AF). Patients and methods Fifty patients with lone AF were referred to our sleep unit from the Department of Cardiology at the University Hospital. Lone AF was defined as AF in patients without cardiac structural abnormality and less than 60 years of age. All patients were subjected to a detailed history with stress on the number and date of documented episodes of AF and how it was terminated, OSA symptoms (excessive daytime sleepiness, witnessed apnea, loud habitual snoring, and nocturnal choking), and OSA screening questionnaires. ENT and cardiac examination by a specialist was done. Full-night attended polysomnography was performed on full night. Results The median apnea-hypopnea index in the studied group was 10.8 (range, 0.4-69.4). There were 21 (42.0%) non-OSA patients, while there were 29 (58%) OSA patients. There were eight (27.6%) mild OSA patients. Moderate OSA patients were 10 (34.5%). Severe OSA patients were 11 (37.9%). Median of the frequency of AF episodes in the last 1 year was significantly higher in the OSA group than in the normal group (P=0.01). No significant difference was present between both groups as regards the number of nocturnal arrhythmias not related to respiratory events. The frequency of paroxysmal AF episodes during the last year shows a significant positive correlation with severity of OSA, desaturation index, and total arousal index. Conclusion The results of our study support our hypothesis that OSA is a risk factor for AF. We should investigate patients with lone AF for the possibility of OSA. [ABSTRACT FROM AUTHOR]

BackgroundCigarette smoking is a risk factor for atrial fibrillation (AF), but whether secondhand smoke (SHS) impacts the risk of AF remains unknown.ObjectiveTo determine if SHS exposure is associated with an increased risk of AF.MethodsWe performed a cross-sectional analysis of data from participants enrolled in the Health eHeart Study, an internet-based, longitudinal cardiovascular cohort study, who completed baseline SHS exposure and medical conditions questionnaires. SHS was assessed through a validated 22-question survey, and prevalent AF was assessed by self-report, with validation of a subset (n = 42) by review of electronic medical records.ResultsOf 4976 participants, 593 (11.9%) reported having AF. In unadjusted analyses, patients with AF were more likely to have been exposed to SHS in utero, as a child, as an adult, at home, and at work. After multivariable adjustment for potential confounders, having had a smoking parent during gestational development (OR 1.37, 95% CI 1.08-1.73, P = .009) and residing with a smoker during childhood (OR 1.40, 95% CI 1.10-1.79, P = .007) were each significantly associated with AF. Both positive associations were more pronounced among patients without risk factors for AF (P values for interaction

Atrial fibrillation (AF) has a heterogeneous clinical presentation. It can occur: (a) in the presence or absence of detectable heart disease, and, (b) with or without related symptoms. Its prognosis in terms of thromboembolism and mortality is most benign when applied to young individuals (aged less than 60 years) without clinical orecho cardio graphic evidence of cardiopulmonary disease [termed "lone AF"]. However, by virtue of aging or because of the development of concomitant cardiovascular disorders, patients move out of the lone AF category over time, accompanied by increased risks for thromboembolism and mortality. Thus, underlying and/or associated comorbidities must play an important role in the presentation and consequences of patients with AF. While, no doubt, most clinicians likely appreciate that the majority of the AF patients they see have associated cardiovascular, pulmonary, metabolic, endocrinologic, genetic, and/or other disorders, it is not clear how much they appreciate that these disorders directly relate to the presenting symptoms and to the risks from AF in addition to their role as risk factors (or markers) for AF. This issue is the subject of this review manuscript. [ABSTRACT FROM AUTHOR]

OBJECTIVES AND BACKGROUND: Studies assessing the unicentric and prospective comparison of efficacy of cryoballoon pulmonary vein isolation in idiopathic and non-idiopathic atrial fibrillation (AF) patients are missing. The aim of this study was to compare a single procedural outcome in these subgroups of AF patients. METHODS: A total of 208 patients with drug resistant AF were included in this study. Among them, 36 patients had idiopathic AF and 172 patients had non-idiopathic AF. The efficacy endpoint was freedom from any atrial arrhythmia lasting >30 s after a 3-months blanking period. RESULTS: The freedom from atrial arrhythmias without antiarrhythmic drugs after 1 and 3 years of follow-up, respectively, was 85.2 % and 70.4 % in patients with idiopathic AF; and 64.6 % and 39.9 % in patients with non-idiopathic AF (p=0.021). Moreover, the success rate when analysing only paroxysmal AF patients after 1 and 3 years of follow-up, respectively, was 95.7 % and 82 % in patients with idiopathic AF; and 72.6 % and 47 % in patients with non-idiopathic AF (p=0.022). CONCLUSIONS: A single cryoballoon pulmonary vein isolation was more effective in preventing atrial arrhythmias relapses in idiopathic AF patients compared to non-idiopathic AF patients. The best efficacy outcomes were observed in patients with paroxysmal idiopathic AF (Tab. 5, Fig. 2, Ref. 25). [ABSTRACT FROM AUTHOR]

Introduction: Cryoballoon (CB)‐guided ablation of atrial fibrillation (AF) is established in symptomatic AF patients. This study sought to determine the safety and efficacy of CB pulmonary vein isolation (PVI) in young adults. Methods and Results: A total of 93 consecutive patients aged <45 years referred to our center for AF ablation were included in this observational study. All patients received CB‐guided PVI according to a standardized institutional protocol. Follow‐up was performed in our outpatient clinic using 72‐h Holter monitoring and periodic telephone interview. Recurrence was defined as any AF/atrial tachycardia (AT) episode >30 s following a 3‐month blanking period. A propensity matched control group consisting of patients older than 45 years were used for further evaluation. Mean age was 35 ± 7 years, 22% suffered from persistent AF, 85% were male. Mean follow‐up was 2.6 ± 2 years. At the end of the observational period, 83% of patients were free of any AF/AT episodes. There was an excellent overall 12‐month success rate of 92%. In comparison to a matched group the overall recurrence rate was noticeably lower in the young group (15% vs. 27%). Increasing age was associated with a hazard ratio of 1.16 for recurrence. In a multivariate analysis model, left atrial diameter remained as significant predictor of AF/AT recurrence. The complication rate was low, no permanent phrenic nerve palsy was observed. Conclusion: CB‐guided PVI in young adults is safe and effective with favorable long‐term results. It may be considered as first‐line therapy in this relatively healthy population. [ABSTRACT FROM AUTHOR]

Aims: Data on patient characteristics, prevalence, and outcomes of atrial fibrillation (AF) patients without traditional risk factors, often labelled 'lone AF', are sparse.Methods and Results: The RE-LY AF registry included 15 400 individuals who presented to emergency departments with AF in 47 countries. This analysis focused on patients without traditional risk factors, including age ≥60 years, hypertension, coronary artery disease, heart failure, left ventricular hypertrophy, congenital heart disease, pulmonary disease, valve heart disease, hyperthyroidism, and prior cardiac surgery. Patients without traditional risk factors were compared with age- and region-matched controls with traditional risk factors (1:3 fashion). In 796 (5%) patients, no traditional risk factors were present. However, 98% (779/796) had less-established or borderline risk factors, including borderline hypertension (130-140/80-90 mmHg; 47%), chronic kidney disease (eGFR < 60 mL/min; 57%), obesity (body mass index > 30; 19%), diabetes (5%), excessive alcohol intake (>14 units/week; 4%), and smoking (25%). Compared with patients with traditional risk factors (n = 2388), patients without traditional risk factors were more often men (74% vs. 59%, P < 0.001) had paroxysmal AF (55% vs. 37%, P < 0.001) and less AF persistence after 1 year (21% vs. 49%, P < 0.001). Furthermore, 1-year stroke occurrence rate (0.6% vs. 2.0%, P = 0.013) and heart failure hospitalizations (0.9% vs. 12.5%, P < 0.001) were lower. However, risk of AF-related re-hospitalization was similar (18% vs. 21%, P = 0.09).Conclusion: Almost all patients without traditionally defined AF risk factors have less-established or borderline risk factors. These patients have a favourable 1-year prognosis, but risk of AF-related re-hospitalization remains high. Greater emphasis should be placed on recognition and management of less-established or borderline risk factors. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) in lifetime athletes (e.g., ≥5 years of participation) is a growing concern but remains enigmatic. Intriguingly, a direct relationship between lifetime training hours and risk of developing AF exists. Professionals in exercise and sport science are at the forefront to help recognize symptoms and direct the athlete to appropriate medical clinicians for expedient care. Although AF in athletes is usually not accompanied by structural heart disease or stroke risk factors (i.e., termed lone AF), it may, nonetheless, pose health risks. In this study, we review various types of AF, proposed mechanisms, and treatment strategies for athletes with AF. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is a common arrhythmia characterized by uncoordinated atrial electrical activity. Lone AF occurs in the absence of traditional risk factors and is frequently observed in male endurance athletes, who face a 2- to 5-fold higher risk of AF compared with healthy, moderately active males. Our understanding of how endurance exercise contributes to the pathophysiology of lone AF remains limited. This study aimed to characterize the circulating protein fluctuations during high-intensity exercise as well as explore potential biomarkers of exercise-associated AF., Methods and Results: A prospective cohort of 12 male endurance cyclists between the ages of 40 and 65 years, 6 of whom had a history of exercise-associated AF, were recruited to participate using a convenience sampling method. The circulating proteome was subsequently analyzed using multiplex immunoassays and aptamer-based proteomics before, during, and after an acute high-intensity endurance exercise bout to assess temporality and identify potential markers of AF. The endurance exercise bout resulted in significant alterations to proteins involved in immune modulation (eg, growth/differentiation factor 15), skeletal muscle metabolism (eg, α-actinin-2), cell death (eg, histones), and inflammation (eg, interleukin-6). Subjects with AF differed from those without, displaying modulation of proteins previously known to have associations with incident AF (eg, C-reactive protein, insulin-like growth factor-1, and angiopoietin-2), and also with proteins having no previous association (eg, tapasin-related protein and α 2 -Heremans-Schmid glycoprotein)., Conclusions: These findings provide insights into the proteomic response to acute intense exercise, provide mechanistic insights into the pathophysiology behind AF in athletes, and identify targets for future study and validation.

To evaluate the frequency of dilated cardiomyopathy (DCM) and cardiac death (CD) in Irish wolfhounds (IW) with subclinical atrial fibrillation (AF) and to compare cardiac and all-cause mortality to those of a contemporaneous control group of apparently healthy IW with sinus rhythm. Fifty-two IW with AF, but without echocardiographic evidence of DCM or other cardiac disease, and an age- and gender-matched control cohort of 52 apparently healthy IW. Data from 1552 IW were retrospectively evaluated. Fifty-two dogs with subclinical AF were compared with 52 IW controls. Time from initial diagnosis to development of DCM was recorded, and survival data were analyzed using cumulative incidence functions. 26/52 AF dogs developed DCM. At study end, in the AF and control group each, 49/52 AF dogs had died, three remained alive. Death in the AF cohort was attributed to CD in 22/49 dogs (12 congestive heart failure [CHF], 10 sudden cardiac deaths [SCD]), while 27 dogs died from non-CD. In the control group, significantly fewer dogs developed DCM (11/52 dogs, p =0.004), even fewer died from CD (5/49; three CHF, two SCD; p =0.001). The odd ratios (95% confidence interval) for dogs with AF vs. controls to develop DCM was 3.7 (1.6–8.8) and to die from CD was 7.2 (2.4–21.2). Median all-cause survival for AF IWs (CD, 36.3 months; non-CD, 33.2 months) did not differ significantly from the control group (CD, 28.6 months, p =0.377; non-CD, 45.3 months, p =0.631). IW with subclinical AF commonly develop DCM and die from cardiac death. [ABSTRACT FROM AUTHOR]

Secondary tricuspid regurgitation (TR) caused by right ventricular enlargement in the setting of left heart disease/pulmonary hypertension has been well described. In contrast, that associated with right atrial enlargement—atrial functional TR (AF‐TR)—remains largely underappreciated. AF‐TR most often occurs in the setting of lone atrial fibrillation, although it is also seen in its absence (idiopathic AF‐TR). Several recent studies have found that the prevalence, hemodynamic significance, and prognosis of AF‐TR are not inconsequential, suggesting increased physician awareness of this novel clinical entity is warranted. This article discusses the pathogenesis, echocardiographic findings, and treatment of this underappreciated cause of secondary TR. [ABSTRACT FROM AUTHOR]

Recent studies lend credibility to the notion that lone atrial fibrillation (AF) can cause functional mitral regurgitation (MR), commonly referred to as atrial functional MR (AF‐MR). The conventional view holds that left atrial enlargement associated with AF causes annular dilatation which gradually moves the mitral valve leaflets apart resulting in inadequate coaptation and regurgitation. Recent findings, however, suggest that AF‐MR is not solely related to left atrial remodeling, but that important structural and functional abnormalities of the left ventricle also play a role in its pathogenesis. [ABSTRACT FROM AUTHOR]

Receptor activator of nuclear factor-κB ligand (RANKL) had been confirmed contributing to the development and progression of AF by regulating atrial structural remodeling. But the involved genetic mechanism is unknown. We intended to explore the association between the polymorphism RANKL −1816C>G (rs7984870) and susceptibility and prognosis of lone AF. RANKL rs7984870 was genotyped in a case-control study of 828 patients and 834 controls in Chinese population. The CG and/or CC genotypes had an increased lone AF risk [adjusted odds ratio (OR) 1.20 for CG, OR 2.16 for CC, and OR 1.55 for CG/CC], compared with the GG genotype. Moreover, patients carrying CG/CC genotypes showed a higher possibility of AF recurrence after catheter ablation, compared with patients carrying GG genotype. In a genotype-phenotype correlation analysis using 24 normal left atrial appendage samples, increasing gradients of atrial RANKL expression levels positively correlated with atrial collagen volume fraction were identified in samples with CC, CG and GG genotypes. The in vitro luciferase assays also showed a higher luciferase activity of the −1816 C/C allele than that of the −1816 G/G allele. These results suggested that RANKL rs7984870 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 RANKL in AF. [ABSTRACT FROM AUTHOR]

Little is known about lone atrial fibrillation (AF) in pediatrics and its risk factors due to low prevalence. We sought to determine risk factors and estimate recurrence rates in children with lone AF using a large clinical database. Using the Explorys clinical database, we retrospectively identified patients who were below 20 years of age at the time of their AF diagnosis. Patients with congenital heart disease, cardiomyopathy, prior open heart surgery, or thyroid disease were excluded. Out of 7,969,230 children identified, 1910 had AF and 1570 met the definition of lone AF. The prevalence of lone AF was 7.5 per 100,000 children. In comparison to young children (0-4 years), risk for lone AF increased with age (adjusted odds ratio (aOR) 1.2 [95% CI 0.9-1.5, P = 0.21] in those 5-9 years, aOR 1.7 [95% CI 1.3-2.1, P < 0.001] in those 10-14 years, and aOR 10.7 [95% CI 8.7-13.2, P < 0.001] in those 15-19 years). Risk of lone AF was also higher in males than females (aOR 1.7 [95% CI 1.5-1.9, P < 0.001]), and was higher in obese children (BMI ≥ 95th percentile) versus children with normal BMI (aOR 1.3 [95% CI 1.1-1.5], P < 0.001), but there was no difference between overweight (BMI = 85th-94th percentile) and normal ( P = 0.14). One-month recurrence rate was 15%, and increased with age. In this large pediatric cohort, the prevalence of lone AF was low, but risk was higher in males and increased with age and obesity. Older children with lone AF had higher rates of recurrence. [ABSTRACT FROM AUTHOR]

Objective: Inflammation and autoimmune responses play an important role in recurrence of atrial fibrillation (AF). Serum globulin levels are a commonly used clinical index that represents inflammation and autoimmune response. This study aimed to determine the relationship between baseline serum globulin levels and the risk of recurrence after ablation in lone AF patients. Methods: We enrolled 348 lone AF patients undergoing radiofrequency catheter ablation for the first time for whom complete follow-up data were available. Pre-ablation peripheral venous blood samples were obtained for measurement of serum globulin levels. Results: During the follow-up period of 22 months (range, 6–62), AF recurred in 129 patients (37.1%). Recurrence was associated with a low level of pre-ablation serum globulins. Multiple Cox proportional hazard regression analysis showed that persistent AF, AF duration, left atrial diameter, no amiodarone after ablation, and the serum globulin level in particular were independent predictors of AF recurrence. According to receiver operating characteristic curve analysis, the best diagnostic cut-off serum globulin level was 25.4 g/L, which showed 74.4% sensitivity, 71.3% specificity, and 73.3% accuracy. Conclusion: The baseline low serum globulin level is associated with AF recurrence after first-time ablation in lone AF patients. Therefore, it may be used as a predictor of AF recurrence in these patients. [ABSTRACT FROM AUTHOR]

Introduction: Lone atrial fibrillation (AF) is defined as AF occurring in the absence of any other cardiovascular disease. The prognosis of patients with lone AF varies in previous studies, and the clinical and electroanatomical characteristics of lone AF are unclear. The purpose of this study was to investigate the clinical characteristics of lone AF. Methods: This study included 203 patients (52±13 years old, 144 males) that underwent circumferential pulmonary vein isolation (CPVI) for paroxysmal AF. The mean voltage and total activation time of the individual atria were obtained by using a NavX mapping system and were compared for patients with lone and non-lone AF. Several parameters, including the age, gender, AF duration, and left atrial (LA) diameter were analyzed. Results: Compared with non-lone AF patients, lone AF patients were significantly younger (49±13 years old vs. 58±11 years old, p

Oral anticoagulants (OAC) decrease the thromboembolic risk of non-valvular atrial fibrillation (AF) at the expense of increased bleeding. Over the years, several risk stratification schemes for both stroke and bleeding risk have been devised, among which lately the respective CHA2DS2-VASc and HAS-BLED scores predominate. However, even when the bleeding risk score is high, the guidelines recommend not to withhold OAC at least for patients with high stroke risk, but to attempt to concomitantly modify the conditions contributing to the high bleeding risk. The CHA2DS2- VASc score has been considered more reliable than other scores in identifying "truly low-risk" patients who do not require OAC, in whom the risk of bleeding may negate the protective effect of OAC. Some have suggested more complex schemes to better identify very low risk patients, but these schemes may lead to more extensive and costly assessments to decide on a relatively simple question, i.e. the need or not for anticoagulation therapy. In the era of non-vitamin K oral anticoagulants (NOACs), this may not be necessary any more, and a simple recommendation of providing every AF patient with OAC therapy may turn out to be a more practical and realistic approach, as long as these newer agents remain safe and effective. [ABSTRACT FROM AUTHOR]

To investigate left atrium (LA) strain properties of patients with lone atrial fibrillation (LAF) and to assess relationships between LA strain parameters and total atrial conduction time measured with tissue Doppler imaging (PA-TDI). The study population consisted of 53 patients with LAF. The control group was comprised of 50 normal volunteers. Conventional echocardiography indices were measured. Mitral annular velocities and PA-TDI were assessed with TDI. Two-dimensional speckle-tracking echocardiography (2D-STE) was used to assess LA segmental strain and strain rate. Compared with the control group, PA-TDI was significantly prolonged and LA myocardial Ss, SRs, Sa, and SRa were significantly decreased in the LAF group (all P < 0.001). In the control group, LA myocardial Ss (γ = -0.486, P < 0.01), SRs (γ = -0.436, P < 0.01), and Sa (γ = -0.360, P < 0.05) were correlated negatively with PA-TDI. LA myocardial SRa (γ = 0.377, P < 0.01) was correlated positively with PA-TDI. In the LAF group, LA myocardial Ss (γ = -0.429, P < 0.01), SRs (γ = -0.468, P < 0.01), and Sa (γ = -0.380, P < 0.05) were also correlated negatively, and SRa (γ = 0.390, P < 0.01) was correlated positively, with PA-TDI. Multivariate logistic regression identified PA-TDI as the only predictor of AF onset (OR 1.39; 95 % CI 1.02-1.54; P < 0.01). LA strain parameters were decreased and PA-TDI was prolonged in patients with LAF. Structural remodeling of the LA, assessed by 2D-STE, was correlated with electrical remodeling, determined by PA-TDI. Prolonged PA-TDI was independently associated with AF onset. [ABSTRACT FROM AUTHOR]

Second-Generation Cryoballoon Ablation Background Lone atrial fibrillation (LAF) develops in younger individuals without cardiovascular or pulmonary disease. As pulmonary vein isolation has been recognized as an optimal treatment for drug-resistant atrial fibrillation, cryoballoon ablation with second-generation balloon (CB-A) may be an ideal solution for LAF patients. Objective The aim of this study was to investigate acute success, periprocedural complications and outcome over a 12-month follow-up period in a cohort of patients having undergone PV isolation (PVI) for LAF using CB-A technology. Methods A total of 75 consecutive patients (50 male, mean age 47 ± 12 years) with a diagnosis of lone paroxysmal atrial fibrillation who underwent pulmonary vein isolation (PVI) by CB-A from June 2012 were included. All patients underwent this procedure with the 28 mm CB-A. A total of 299 PVs (100%) could be isolated with CB-A alone. Results The freedom from AF recurrence after a single procedure was 92% of patients during the entire 13-month follow-up. When considering a blanking period (BP) of 3 months, success rate was 93.3%. Transient phrenic nerve palsy (PNP) was the most frequent complication, occurring in 5.3% of individuals (4 patients); complete recovery was documented for all of these patients prior to hospital discharge. Conclusions CB-A is extremely effective in achieving PVI and affords freedom from AF at 13-month follow-up in 93% of young patients affected by drug-resistant LPAF following a 3-month BP. The most frequent complication observed was PNP, which reverted prior to discharge in all patients. [ABSTRACT FROM AUTHOR]

Background: The nosological nature of "idiopathic" arrhythmias and the effect of etiotropic and pathogenetic treatment are often unknown. Methods And Results: 19 patients (42.6±11.3 years, 9 women) with atrial fibrillation (n = 16), supraventricular (n = 10) and ventricular (n= 4) premature beats, supraventricular (n = 2) and ventricular tachycardia (n = 1), left bundle branch block (n= 2), AV block (n = 2) without structural heart changes. Viruses were identified (polymerase chain reaction, PCR) along with measurement of anti-heart antibodies (AHA) and endomyocardial biopsy (EM B). EMB allowed to establish diagnosis in all patients: 1) infectious-immune myocarditis (n = 11, parvovirus-positive in 1), 2) parvovirus-positive endomyocarditis (n = 1), 3) systemic (n = 2) and myocardial (n = 1) vasculitis, 4) Fabry's disease (n = 1), 5) arrhythmogenic right ventricular dysplasia (n = 1), 6) unspecified genetic cardiomyopathy (n = 2, herpes virus 6 one positive). Level of AHA had the greatest significance for myocarditis diagnostics. All patients with myocarditis/vasculitis had background therapy: acyclovir (n = 10), IV immunoglobulin (n = 2), meloxicam (n = 12), hydroxychloroquine (n = 15), steroids (n = 14, 31.1±12.5 mg/day), azathioprine 150 mg/day (n = 2). Median follow-up was 4 years. Treatment significantly reduced the rate of arrhythmias (8 [5;8] to 3 [1.25;7.75] points); disappearance of bundle branch block was noted. Conclusion: EMB allowed to diagnose immune-mediated inflammatory diseases in 78.9% patients with 'idiopathic' arrhythmias and genetic diseases in 21.1%. Background therapy of myocarditis improved the antiarrhythmic efficiency, and allowed the best premed for interventional treatment. [ABSTRACT FROM AUTHOR]

Catheter Ablation for 'Lone' Atrial Fibrillation Background Atrial fibrillation in otherwise healthy young patients has been termed 'lone' atrial fibrillation (AF). The best treatment choice is still under discussion. The aim of this study was to report on efficacy and safety of catheter ablation. Methods Among 855 patients referred to our center between 2011 and 2013, 76 (9%) met the diagnostic criteria for lone AF (mean age 45 ± 8 years; mean LA diameter 37 ± 4 mm; paroxysmal AF 82%; persistent AF 18%). The primary endpoint was freedom from any atrial tachycardia after the first ablation; the secondary endpoint was freedom from any atrial tachycardia after the last ablation procedure without antiarrhythmic drugs. Results The primary endpoint occurred in 56 patients (74%) after a mean follow-up time of 444 ± 344 days. The secondary endpoint occurred in 73 patients (96%) after a mean of 1.3 ablations/patient during a follow-up time of 459 ± 366 days. The risk of AF recurrence was not influenced by AF duration or by the type of AF (paroxysmal versus persistent). In a multivariate regression analysis smoking (P = 0.001), first degree atrioventricular block (P = 0.001), and early (< 3 months) AF recurrence (P = 0.001) were independently associated with a higher risk of AF recurrence. Major peri-procedural adverse events did not occur. Conclusions Catheter ablation in young healthy patients is highly effective and safe. The outcomes are maintained during long-term follow-up irrespective of preoperative AF duration. Patients with AF recurrence were more likely to smoke, have first degree AV block and early AF recurrence. [ABSTRACT FROM AUTHOR]

Background: Minimally invasive surgical treatment of lone atrial fibrillation (AF) is an alternative for AF that is refractory to medical treatment. We present long-term results of standalone surgical ablation of AF using a bipolar ablation device in 91 consecutive patients.Methods: This was an observational, retrospective study of 91 patients (77 % males; mean age, 53 ± 10 years [range, 23-75 years]) who underwent minimally invasive standalone surgical ablation of persistent and longstanding persistent AF using a bipolar ablation device from 2008 to 2014. Mean follow-up was 60 ± 21 months. The absence of arrhythmia was confirmed at 3, 6, and 12 months, and annually thereafter, with 24-hour Holter monitoring.Results: The mean duration of preoperative AF was 6.5 ± 5.4 years. Persistent AF was present in 86 % of patients and longstanding persistent AF in 14 %. Mean left atrial diameter was 4.3 ± 0.8 cm. There were two postoperative strokes (2 %) and three conversions to median sternotomy (3 %). Permanent pacemakers were implanted in six (7 %) patients. There were no intra- or postoperative deaths. At 1, 2, 3, 4, and 5 years postoperatively, freedom from AF was 59, 45, 41, 38, and 38 % of patients, respectively. The failure to achieve pulmonary vein isolation was the only independent predictor of long-term recurrence of AF (HR -3 [95 % CI 1,858 to 8,586], p = 0,001). There was a tendency towards higher rates of SR at long term follow up in patients with pulmonary vein isolation if division of ligament of Marshall was performed (HR - 2 [95 % CI 0.987 to 4,202], p = 0,067).Conclusions: In the present series, the efficacy of epicardial surgical ablation was similar to that reported previously. The rate of arrhythmia recurrence increased over time. Achieving pulmonary vein isolation is essential to AF elimination. The division of ligament of Marshall could contribute to improved rates of SR restoration in patients with persistent or long-standing persistent AF if PVI is achieved. [ABSTRACT FROM AUTHOR]

Aims: The role of high-intensity exercise and other emerging risk factors in lone atrial fibrillation (Ln-AF) epidemiology is still under debate. The aim of this study was to analyse the contribution of each of the emerging risk factors and the impact of physical activity dose in patients with Ln-AF.Methods and Results: Patients with Ln-AF and age- and sex-matched healthy controls were included in a 2:1 prospective case-control study. We obtained clinical and anthropometric data transthoracic echocardiography, lifetime physical activity questionnaire, 24-h ambulatory blood pressure monitoring, Berlin questionnaire score, and, in patients at high risk for obstructive sleep apnoea (OSA) syndrome, a polysomnography. A total of 115 cases and 57 controls were enrolled. Conditional logistic regression analysis associated height [odds ratio (OR) 1.06 [1.01-1.11]], waist circumference (OR 1.06 [1.02-1.11]), OSA (OR 5.04 [1.44-17.45]), and 2000 or more hours of cumulative high-intensity endurance training to a higher AF risk. Our data indicated a U-shaped association between the extent of high-intensity training and AF risk. The risk of AF increased with an accumulated lifetime endurance sport activity ≥ 2,000 h compared with sedentary individuals (OR 3.88 [1.55-9.73]). Nevertheless, a history of <2000 h of high-intensity training protected against AF when compared with sedentary individuals (OR 0.38 [0.12-0.98]).Conclusion: A history of ≥ 2,000 h of vigorous endurance training, tall stature, abdominal obesity, and OSA are frequently encountered as risk factors in patients with Ln-AF. Fewer than 2000 total hours of high-intensity endurance training associates with reduced Ln-AF risk. [ABSTRACT FROM AUTHOR]

KCNQ1 Mutations in Early-Onset Lone AF Introduction Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. The potassium current IKs is essential for cardiac repolarization. Gain-of-function mutation in KCNQ1, the gene encoding the pore-forming α-subunit of the IKs channel (KV7.1), was the first ion channel dysfunction to be associated with familial AF. We hypothesized that early-onset lone AF is associated with a high prevalence of mutations in KCNQ1. Methods and Results We bidirectionally sequenced the entire coding sequence of KCNQ1 in 209 unrelated patients with early-onset lone AF (<40 years) and investigated the identified mutations functionally in a heterologous expression system. We found 4 nonsynonymous KCNQ1 mutations (A46T, R195W, A302V, and R670K) in 4 unrelated patients (38, 31, 39, and 36 years, respectively). None of the mutations were present in the control group (n = 416 alleles). No other mutations were found in genes previously associated with AF. The mutations A46T, R195W, and A302V have previously been associated with long-QT syndrome. In line with previous reports, we found A302V to display a pronounced loss-of-function of the IKs current, while the other mutants exhibited a gain-of-function phenotype. Conclusions Mutations in the IKs channel leading to gain-of-function have previously been described in familial AF, yet this is the first time a loss-of-function mutation in KCNQ1 is associated with early-onset lone AF. These findings suggest that both gain-of-function and loss-of-function of cardiac potassium currents enhance the susceptibility to AF. [ABSTRACT FROM AUTHOR]

Background: Since its introduction in 1953, lone atrial fibrillation (LAF) has not been defined with any consistency, resulting in an enormous variation in the way the term is used. Inherent to this, results from studies vary considerably. Many predisposing factors and pathogenic influences have been discovered over the past years, which raise the question if the term LAF should still be used and if the treatment should be different from non-lone atrial fibrillation (non-LAF). Therefore this systematic review on LAF provides an overview of risk factors and triggers, the second part focuses on the application of catheter and surgical ablation techniques. Methods: A systematic literature search was performed in the PubMed database. All identified articles were screened and checked for eligibility by the two authors. Additional literature was sought by screening the references of eligible articles. Results: The term LAF is used very variably and inconsistently, and results concerning etiology in different studies are often contradictory. Overall finding is that LAF has many risk factors (e.g. subclinical atherosclerosis, enlarged left atrial volume, left ventricular dysfunction, occult hypertension, arterial stiffness, systemic inflammation and genetic factors) and can be induced by many different triggers (e.g. use of substances, endurance sports, mental stress and sleeping). However, compared to non-LAF there are no unique mechanisms related to LAF. Concerning the therapy, catheter ablation is first or second choice after antiarrhythmic drugs, however surgical and hybrid approaches may be indicated in complex cases. Conclusions: Insufficient evidence exists to consider LAF as a real, isolated and useful entity. A re-definition or even avoiding the use of the term LAF might be appropriate. [ABSTRACT FROM AUTHOR]

Although atrial fibrillation (AF) development has been demonstrated to be associated with underlying cardiovascular conditions such as hypertension, valvular heart disease or diabetes mellitus; in a subset of relatively younger patients, no cardiopulmonary disease diagnosis can be established. AF patients younger than 60 years without clinical or echocardiographic evidence of cardiopulmonary disease are defined as lone AF patients. Despite the decrease in lone AF prevalence due to advances in understanding of AF pathogenesis, there are still issues yet to be resolved. Future studies are needed to demonstrate the cost- effectiveness of the routine use of more advanced diagnostic tools, such as non- invasive assessment of endothelial function, autoimmune markers or genetic screening and whether they would have clinical implications on treatment of lone AF. This review focuses on the suggested mechanisms in lone AF initiation and maintenance. [ABSTRACT FROM AUTHOR]

Background: Pathophysiologic mechanisms underlying lone atrial fibrillation (AF) have not been clearly demonstrated yet. Emerging evidence has indicated that autoimmunity may play a role in the development of AF. Relationship between serum anti-M2-muscarinic receptor autoantibody (anti-M2-R) and anti-β1-adrenergic receptor autoantibody (anti-β1-R) levels and lone paroxysmal atrial fibrillation (PAF) has not been investigated. We aimed to compare anti-M2-R and anti-β1-R levels between lone PAF patients and healthy control subjects. Methods and results: 75 patients with lone PAF (age: 52.80 ± 6.80 years, 53 % male) and 75 healthy control subjects (age: 53.30 ± 6.80 years, 54 % male) were enrolled in the study. Serum anti-M2-R and anti-β1-R levels were measured by ELISA and compared between two groups. Anti-M2-R [142.30 (77.65-400.00) vs. 69.00 (39.48-299.04) ng/mL; p < 0.001) and anti-β1-R [102.56 (65.18-348.41) vs. 44.17 (30.89-158.54) ng/mL; p < 0.001] levels were significantly higher in patients with lone PAF compared to healthy controls. Multivariate regression analysis showed that left atrial diameter (OR: 1.471, p < 0.001), hs-CRP(OR: 1.940, p < 0.001), anti-M2-R (OR: 1.158, p < 0.001) and anti-β1-R (OR: 1.296, p < 0.001) levels were independent predictors for the presence of lone PAF. Using a cut-off level of 101.83 ng/mL, anti-M2-R levels predicted presence of lone PAF with a sensitivity of 94.68 % and specificity of 81.33 %. Anti-β1-R levels predicted presence of lone PAF with a sensitivity of 92.00 % and specificity of 73.30 %, using a cut-off level of 72.16 ng/mL. Conclusion: Our results demonstrated that higher serum anti-M2-R and anti-β1-R levels are associated with lone PAF. Autoantibodies related to autonomic system may play an important role in the development of lone AF. [ABSTRACT FROM AUTHOR]