Comprehensive risk reduction in patients with atrial fibrillation: emerging diagnostic and therapeutic options--a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference.

While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF.

[1]  Thomas Meitinger,et al.  Common Variants in KCNN3 are Associated with Lone Atrial Fibrillation , 2010, Nature Genetics.

[2]  O. Melander,et al.  Atrial fibrillation in the Malmö diet and cancer study: a study of occurrence, risk factors and diagnostic validity , 2010, European Journal of Epidemiology.

[3]  Gregory Y H Lip,et al.  A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. , 2010, Chest.

[4]  E. Unger,et al.  Anticoagulant options--why the FDA approved a higher but not a lower dose of dabigatran. , 2011, The New England journal of medicine.

[5]  A M Tonkin,et al.  Atrial fibrillation after coronary artery bypass grafting is associated with sympathetic activation. , 1995, The Annals of thoracic surgery.

[6]  E. Aliot,et al.  Delayed rhythm control of atrial fibrillation may be a cause of failure to prevent recurrences: reasons for change to active antiarrhythmic treatment at the time of the first detected episode. , 2007, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[7]  Ulrich Schotten,et al.  PITX2c Is Expressed in the Adult Left Atrium, and Reducing Pitx2c Expression Promotes Atrial Fibrillation Inducibility and Complex Changes in Gene Expression , 2011, Circulation. Cardiovascular genetics.

[8]  G. Breithardt,et al.  Brugada Syndrome and Supraventricular Tachyarrhythmias: A Novel Association? , 2001, Journal of cardiovascular electrophysiology.

[9]  M. Allessie,et al.  High-density mapping of electrically induced atrial fibrillation in humans. , 1994, Circulation.

[10]  M. Geleijnse,et al.  Left atrial Frank–Starling law assessed by real-time, three-dimensional echocardiographic left atrial volume changes , 2007, Heart.

[11]  J. Murabito,et al.  Temporal Relations of Atrial Fibrillation and Congestive Heart Failure and Their Joint Influence on Mortality The Framingham Heart Study , 2003, Circulation.

[12]  A. Capucci,et al.  Improving Stroke Risk Stratification Using the CHADS2 and CHA2DS2-VASc Risk Scores in Patients With Paroxysmal Atrial Fibrillation by Continuous Arrhythmia Burden Monitoring , 2011, Stroke.

[13]  D. Singer,et al.  Moving the Tipping Point: The Decision to Anticoagulate Patients With Atrial Fibrillation , 2011, Circulation. Cardiovascular quality and outcomes.

[14]  P. Kirchhof,et al.  Antithrombotic management of atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing coronary stenting: executive summary--a Consensus Document of the European Society of Cardiology Working Group on Thrombosis, endorsed by the European Heart Rhythm Association (EHRA) a , 2010, European heart journal.

[15]  E. Aliot,et al.  Indications for the use of diagnostic implantable and external ECG loop recorders. , 2009, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[16]  B. Gersh,et al.  Structural and functional remodeling of the left atrium: clinical and therapeutic implications for atrial fibrillation. , 2008, Journal of the American College of Cardiology.

[17]  Salim Yusuf,et al.  Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial , 2010, The Lancet.

[18]  Nicolas Derval,et al.  Clinical value of fibrillatory wave amplitude on surface ECG in patients with persistent atrial fibrillation , 2009, Journal of Interventional Cardiac Electrophysiology.

[19]  B. Gersh,et al.  Long-Term Progression and Outcomes With Aging in Patients With Lone Atrial Fibrillation: A 30-Year Follow-Up Study , 2007, Circulation.

[20]  H. Hense,et al.  The aging process of the heart: obesity is the main risk factor for left atrial enlargement during aging the MONICA/KORA (monitoring of trends and determinations in cardiovascular disease/cooperative research in the region of Augsburg) study. , 2009, Journal of the American College of Cardiology.

[21]  Joshua J. E. Blauer,et al.  Left Atrial Strain and Strain Rate in Patients With Paroxysmal and Persistent Atrial Fibrillation: Relationship to Left Atrial Structural Remodeling Detected by Delayed-Enhancement MRI , 2010, Circulation. Cardiovascular imaging.

[22]  J. Cox,et al.  Differences between perspectives of physicians and patients on anticoagulation in patients with atrial fibrillation: observational study. , 2001, BMJ : British Medical Journal.

[23]  S. Greenberg,et al.  Patient-Specific Decision-Making for Warfarin Therapy in Nonvalvular Atrial Fibrillation: How Will Screening With Genetics and Imaging Help? , 2008, Stroke.

[24]  M. Allessie,et al.  Configuration of unipolar atrial electrograms during electrically induced atrial fibrillation in humans. , 1997, Circulation.

[25]  Ralph B D'Agostino,et al.  Parental atrial fibrillation as a risk factor for atrial fibrillation in offspring. , 2004, JAMA.

[26]  Joshua J. E. Blauer,et al.  New magnetic resonance imaging based method to define extent of left atrial wall injury after the ablation of atrial fibrillation , 2008 .

[27]  S. Yusuf,et al.  Dabigatran versus warfarin in patients with atrial fibrillation. , 2009, The New England journal of medicine.

[28]  Kenneth A Ellenbogen,et al.  2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (updating the 2006 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. , 2011, Circulation.

[29]  Robby Nieuwlaat,et al.  Progression from paroxysmal to persistent atrial fibrillation clinical correlates and prognosis. , 2010, Journal of the American College of Cardiology.

[30]  J. De Sutter,et al.  Intra- and interatrial asynchrony in patients with heart failure. , 2007, The American journal of cardiology.

[31]  J. Nielsen,et al.  Is the risk of atrial fibrillation higher in athletes than in the general population? A systematic review and meta-analysis. , 2009, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[32]  D. Levy,et al.  Development of a risk score for atrial fibrillation (Framingham Heart Study): a community-based cohort study , 2009, The Lancet.

[33]  Jeroen J. Bax,et al.  Natriuretic peptide levels predict recurrence of atrial fibrillation after radiofrequency catheter ablation. , 2011, American heart journal.

[34]  Paul A Friedman,et al.  Association of Atrial Fibrillation and Obstructive Sleep Apnea , 2004, Circulation.

[35]  G. Lip,et al.  Atrial fibrillation following cardiac surgery: clinical features and preventative strategies. , 2008, European heart journal.

[36]  Joshua J. E. Blauer,et al.  Detection and Quantification of Left Atrial Structural Remodeling With Delayed-Enhancement Magnetic Resonance Imaging in Patients With Atrial Fibrillation , 2009, Circulation.

[37]  D. Levy,et al.  Prevention of Atrial Fibrillation: Report From a National Heart, Lung, and Blood Institute Workshop , 2009, Circulation.

[38]  Hidekazu Tomimoto,et al.  SILENT ISCHEMIC INFARCTS ARE ASSOCIATED WITH HEMORRHAGE BURDEN IN CEREBRAL AMYLOID ANGIOPATHY , 2010, Neurology.

[39]  Elsayed Z Soliman,et al.  A clinical risk score for atrial fibrillation in a biracial prospective cohort (from the Atherosclerosis Risk in Communities [ARIC] study). , 2011, The American journal of cardiology.

[40]  Kathleen F. Kerr,et al.  European Ancestry as a Risk Factor for Atrial Fibrillation in African Americans , 2010, Circulation.

[41]  E. Mohammadi,et al.  Barriers and facilitators related to the implementation of a physiological track and trigger system: A systematic review of the qualitative evidence , 2017, International journal for quality in health care : journal of the International Society for Quality in Health Care.

[42]  R. de Caterina,et al.  Mortality predictors and effects of antithrombotic therapies in atrial fibrillation: insights from ACTIVE-W. , 2010, European heart journal.

[43]  M. P. van den Berg,et al.  C-reactive protein and microalbuminuria are associated with atrial fibrillation. , 2005, International journal of cardiology.

[44]  Thomas Meitinger,et al.  Lack of replication in polymorphisms reported to be associated with atrial fibrillation. , 2011, Heart rhythm.

[45]  S. Themistoclakis,et al.  The risk of thromboembolism and need for oral anticoagulation after successful atrial fibrillation ablation. , 2010, Journal of the American College of Cardiology.

[46]  Eric E. Smith,et al.  Variants conferring risk of atrial fibrillation on chromosome 4q25 , 2007, Nature.

[47]  John Camm,et al.  Bleeding risk assessment and management in atrial fibrillation patients: a position document from the European Heart Rhythm Association, endorsed by the European Society of Cardiology Working Group on Thrombosis. , 2011, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[48]  K. Swedberg,et al.  Big men and atrial fibrillation: effects of body size and weight gain on risk of atrial fibrillation in men. , 2009, European heart journal.

[49]  D. Levy,et al.  Relations of Biomarkers of Distinct Pathophysiological Pathways and Atrial Fibrillation Incidence in the Community , 2010, Circulation.

[50]  E. Benjamin,et al.  P wave duration is associated with cardiovascular and all-cause mortality outcomes: the National Health and Nutrition Examination Survey. , 2011, Heart rhythm.

[51]  Albert Hofman,et al.  Cigarette smoking and risk of atrial fibrillation: the Rotterdam Study. , 2008, American heart journal.

[52]  S. Yusuf,et al.  Risk of Bleeding With 2 Doses of Dabigatran Compared With Warfarin in Older and Younger Patients With Atrial Fibrillation: An Analysis of the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) Trial , 2011, Circulation.

[53]  Predictors of Thromboembolism in Atrial Fibrillation: II. Echocardiographic Features of Patients at Risk , 1992, Annals of Internal Medicine.

[54]  A. Tveit,et al.  Effect of candesartan and various inflammatory markers on maintenance of sinus rhythm after electrical cardioversion for atrial fibrillation. , 2007, The American journal of cardiology.

[55]  D. Levy,et al.  Relation of multiple inflammatory biomarkers to incident atrial fibrillation. , 2009, The American journal of cardiology.

[56]  Martin O'Donnell,et al.  After Acute Ischemic Stroke : A Systematic Review Noninvasive Cardiac Monitoring for Detecting Paroxysmal Atrial Fibrillation or Flutter , 2007 .

[57]  Bruce M Psaty,et al.  Inflammation as a Risk Factor for Atrial Fibrillation , 2003, Circulation.

[58]  Bertil Olsson,et al.  Outcome parameters for trials in atrial fibrillation: executive summary. , 2007, European heart journal.

[59]  F A Mathewson,et al.  The natural history of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba Follow-Up Study. , 1995, The American journal of medicine.

[60]  G. Breithardt,et al.  Outcome parameters for trials in atrial fibrillation: recommendations from a consensus conference organized by the German Atrial Fibrillation Competence NETwork and the European Heart Rhythm Association. , 2007, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[61]  G. Lamas,et al.  Atrial High Rate Episodes Detected by Pacemaker Diagnostics Predict Death and Stroke: Report of the Atrial Diagnostics Ancillary Study of the MOde Selection Trial (MOST) , 2003, Circulation.

[62]  Salim Yusuf,et al.  Effect of clopidogrel added to aspirin in patients with atrial fibrillation. , 2009, The New England journal of medicine.

[63]  Yasuhiko Takemoto,et al.  Prediction of risk for first age-related cardiovascular events in an elderly population: the incremental value of echocardiography. , 2003, Journal of the American College of Cardiology.

[64]  Paul Schoenhagen,et al.  Left Atrial Epicardial Adiposity and Atrial Fibrillation , 2010, Circulation. Arrhythmia and electrophysiology.

[65]  S. Greenberg,et al.  Beyond hypertension: unraveling the causes of intracerebral hemorrhage. , 2002, Stroke.

[66]  James D. Thomas,et al.  Left atrial strain measured by two-dimensional speckle tracking represents a new tool to evaluate left atrial function. , 2010, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[67]  N. Cook,et al.  A multimarker approach to assess the influence of inflammation on the incidence of atrial fibrillation in women. , 2010, European heart journal.

[68]  Maurice Buchbinder,et al.  Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial , 2009, The Lancet.

[69]  C. Hack,et al.  Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves C-reactive protein and is associated with postoperative arrhythmia. , 1997, Circulation.

[70]  Dirk De Bacquer,et al.  Long-term prognostic value of p-wave characteristics for the development of atrial fibrillation in subjects aged 55 to 74 years at baseline. , 2007, The American journal of cardiology.

[71]  Theodor Landis,et al.  Usefulness of Ambulatory 7-Day ECG Monitoring for the Detection of Atrial Fibrillation and Flutter After Acute Stroke and Transient Ischemic Attack , 2004, Stroke.

[72]  Independent predictors of stroke in patients with atrial fibrillation , 2007, Neurology.

[73]  A. Camm,et al.  Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). , 2010, European heart journal.

[74]  Randy L. Johnson,et al.  Pitx2 prevents susceptibility to atrial arrhythmias by inhibiting left-sided pacemaker specification , 2010, Proceedings of the National Academy of Sciences.

[75]  M. Chiariello,et al.  Determinants of atrial fibrillation development in patients with hypertrophic cardiomyopathy. , 2004, The American journal of cardiology.

[76]  Kenneth A Ellenbogen,et al.  2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (Updating the 2006 Guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. , 2011, Heart rhythm.

[77]  Ulrich Schotten,et al.  Fibrillatory Conduction in the Atrial Free Walls of Goats in Persistent and Permanent Atrial Fibrillation , 2010, Circulation. Arrhythmia and electrophysiology.

[78]  D. Wilber,et al.  Pericardial fat is independently associated with human atrial fibrillation. , 2010, Journal of the American College of Cardiology.

[79]  S. Lévy,et al.  Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial , 2008, The Lancet.

[80]  V. Somers,et al.  Obstructive sleep apnea, obesity, and the risk of incident atrial fibrillation. , 2007, Journal of the American College of Cardiology.

[81]  Nancy R Cook,et al.  Birth weight is a significant risk factor for incident atrial fibrillation. , 2010, Circulation.

[82]  A. Hofman,et al.  Subclinical atherosclerosis and risk of atrial fibrillation: the rotterdam study. , 2007, Archives of internal medicine.

[83]  R. P. Zhu,et al.  Cost-Effectiveness of Dabigatran Compared With Warfarin for Stroke Prevention in Atrial Fibrillation , 2011, Annals of Internal Medicine.

[84]  S. Landas,et al.  Spatial Distribution of Fibrosis Governs Fibrillation Wave Dynamics in the Posterior Left Atrium During Heart Failure , 2007, Circulation research.

[85]  M. Pfeffer,et al.  Atrial fibrillation and risk of clinical events in chronic heart failure with and without left ventricular systolic dysfunction: results from the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) program. , 2006, Journal of the American College of Cardiology.

[86]  Eric Boerwinkle,et al.  Independent Susceptibility Markers for Atrial Fibrillation on Chromosome 4q25 , 2010, Circulation.

[87]  B. Lewis,et al.  Atrial fibrillation and long-term prognosis in patients hospitalized for heart failure: results from heart failure survey in Israel (HFSIS). , 2010, European heart journal.

[88]  A. Nierich,et al.  C-reactive protein is a risk indicator for atrial fibrillation after myocardial revascularization. , 2005, The Annals of thoracic surgery.

[89]  G. Breithardt,et al.  Comprehensive risk reduction in patients with atrial fibrillation: Emerging diagnostic and therapeutic options , 2011, Thrombosis and Haemostasis.

[90]  M. Aguilar,et al.  Adjusted-dose warfarin versus aspirin for preventing stroke in patients with atrial fibrillation. , 2007, Annals of internal medicine.

[91]  P. Kirchhof,et al.  Management of Antithrombotic Therapy in Atrial Fibrillation Patients Presenting with Acute Coronary Syndrome and/or Undergoing Percutaneous Coronary Intervention/ Stenting , 2009, Thrombosis and Haemostasis.

[92]  G. Lip,et al.  Age as a risk factor for stroke in atrial fibrillation patients: implications for thromboprophylaxis. , 2010, Journal of the American College of Cardiology.

[93]  Eric Boerwinkle,et al.  Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry , 2009, Nature Genetics.

[94]  James B Seward,et al.  Left atrial size: physiologic determinants and clinical applications. , 2006, Journal of the American College of Cardiology.

[95]  Francisco Castells,et al.  Noninvasive Mapping of Human Atrial Fibrillation , 2009, Cardiovascular Electrophysiology.

[96]  P. Kirchhof,et al.  Pathophysiological mechanisms of atrial fibrillation: a translational appraisal. , 2011, Physiological reviews.

[97]  T. Lumley,et al.  Risk of new-onset atrial fibrillation in relation to body mass index. , 2006, Archives of internal medicine.

[98]  A. Skanes,et al.  Validation of a New Simple Scale to Measure Symptoms in Atrial Fibrillation: The Canadian Cardiovascular Society Severity in Atrial Fibrillation Scale , 2009, Circulation. Arrhythmia and electrophysiology.

[99]  D. Levy,et al.  Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. , 1994, JAMA.

[100]  E. Kholmovski,et al.  Atrial Fibrosis Helps Select the Appropriate Patient and Strategy in Catheter Ablation of Atrial Fibrillation: A DE‐MRI Guided Approach , 2011, Journal of cardiovascular electrophysiology.

[101]  L H Kuller,et al.  Incidence of and risk factors for atrial fibrillation in older adults. , 1997, Circulation.

[102]  J. Brugada,et al.  Sport practice and the risk of lone atrial fibrillation: a case-control study. , 2006, International journal of cardiology.

[103]  Christopher E Hilker,et al.  Incidence of Newly Detected Atrial Arrhythmias via Implantable Devices in Patients With a History of Thromboembolic Events , 2010, Stroke.

[104]  A. Moss,et al.  Abnormal P‐Wave Morphology Is a Predictor of Atrial Fibrillation Development and Cardiac Death in MADIT II Patients , 2010, Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc.

[105]  Ping-Yen Liu,et al.  Clinical characteristics and outcomes of hypertrophic cardiomyopathy in Taiwan—a tertiary center experience , 2007, Clinical cardiology.

[106]  A. Capucci,et al.  The Relationship Between Atrial High-Rate Episodes and Stroke: The Asymptomatic Stroke and Atrial Fibrillation Evaluation in Pacemaker Patients (ASSERT) Trial , 2010 .

[107]  O. Benavente,et al.  Antithrombotic Therapy To Prevent Stroke in Patients with Atrial Fibrillation , 1999, Annals of Internal Medicine.

[108]  Gregory Y H Lip,et al.  Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. , 2011, Journal of the American College of Cardiology.

[109]  M. Movahed,et al.  Diabetes mellitus is a strong, independent risk for atrial fibrillation and flutter in addition to other cardiovascular disease. , 2005, International journal of cardiology.

[110]  Michel Haissaguerre,et al.  Short QT syndrome: clinical findings and diagnostic-therapeutic implications. , 2006, European heart journal.

[111]  James B Seward,et al.  Left atrial volume predicts cardiovascular events in patients originally diagnosed with lone atrial fibrillation: three-decade follow-up. , 2006, European heart journal.

[112]  Paulus Kirchhof,et al.  Can we improve outcomes in AF patients by early therapy? , 2009, BMC medicine.

[113]  K. Kimura,et al.  Relation of atrial fibrillation to glomerular filtration rate. , 2008, The American journal of cardiology.

[114]  G. Lip,et al.  Risk factors for anticoagulation-related bleeding complications in patients with atrial fibrillation: a systematic review. , 2007, QJM : monthly journal of the Association of Physicians.

[115]  Joshua J. E. Blauer,et al.  Temporal left atrial lesion formation after ablation of atrial fibrillation. , 2009, Heart rhythm.

[116]  K. Stefánsson,et al.  Familial aggregation of atrial fibrillation in Iceland. , 2006, European heart journal.

[117]  S. Siu,et al.  Atrial arrhythmia after surgical closure of atrial septal defects in adults. , 1999, The New England journal of medicine.

[118]  M. Russo,et al.  Histological substrate of atrial biopsies in patients with lone atrial fibrillation. , 1997, Circulation.

[119]  W. Kannel,et al.  Epidemiologic features of chronic atrial fibrillation: the Framingham study. , 1982, The New England journal of medicine.

[120]  A L Waldo,et al.  Simultaneous multisite mapping studies during induced atrial fibrillation in the sterile pericarditis model. Insights into the mechanism of its maintenance. , 1997, Circulation.

[121]  M. Feuring,et al.  Dabigatran etexilate – a novel, reversible, oral direct thrombin inhibitor: Interpretation of coagulation assays and reversal of anticoagulant activity , 2010, Thrombosis and Haemostasis.

[122]  G. Breithardt,et al.  A Patient with “Atrial Torsades de Pointes” , 2000, Journal of cardiovascular electrophysiology.

[123]  J. Brugada,et al.  Identification of a genetic locus for familial atrial fibrillation. , 1997, The New England journal of medicine.

[124]  Curt D. Furberg,et al.  Physical Activity and Incidence of Atrial Fibrillation in Older Adults: The Cardiovascular Health Study , 2008, Circulation.

[125]  B. Maron,et al.  Clinical profile of stroke in 900 patients with hypertrophic cardiomyopathy. , 2002, Journal of the American College of Cardiology.

[126]  S. Greenberg,et al.  White matter lesions, cognition, and recurrent hemorrhage in lobar intracerebral hemorrhage , 2004, Neurology.

[127]  D. Levy,et al.  Obesity and the risk of new-onset atrial fibrillation. , 2004, JAMA.

[128]  L. Fried,et al.  Thyroid status, cardiovascular risk, and mortality in older adults. , 2006, JAMA.

[129]  Massimo Santini,et al.  Monitored atrial fibrillation duration predicts arterial embolic events in patients suffering from bradycardia and atrial fibrillation implanted with antitachycardia pacemakers. , 2005, Journal of the American College of Cardiology.

[130]  Dudley J Pennell,et al.  Reference left atrial dimensions and volumes by steady state free precession cardiovascular magnetic resonance , 2010, Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance.

[131]  L. Kuller,et al.  Alcohol consumption and risk and prognosis of atrial fibrillation among older adults: the Cardiovascular Health Study. , 2007, American heart journal.

[132]  C. Albert,et al.  Caffeine consumption and incident atrial fibrillation in women. , 2010, The American journal of clinical nutrition.

[133]  A. Naidech,et al.  Prior antiplatelet therapy and outcome following intracerebral hemorrhage: A systematic review , 2011, Neurology.

[134]  Ying Wang,et al.  Genomewide association study of leprosy. , 2009, The New England journal of medicine.

[135]  M. Pfeffer,et al.  Prevention of atrial fibrillation in patients with symptomatic chronic heart failure by candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program. , 2006, American heart journal.

[136]  Maurizio Bentivoglio,et al.  Atrial Fibrillation in Hypertension: Predictors and Outcome , 2003, Hypertension.

[137]  G. Breithardt,et al.  Atrial Arrhythmias in Long‐QT Syndrome under Daily Life Conditions: A Nested Case Control Study , 2009, Journal of cardiovascular electrophysiology.

[138]  J. Franklyn,et al.  Association between serum free thyroxine concentration and atrial fibrillation. , 2007, Archives of internal medicine.

[139]  P. Vestergaard,et al.  Overweight and obesity as risk factors for atrial fibrillation or flutter : The Danish Diet, Cancer, and Health Study , 2005 .

[140]  Richard A. Kronmal,et al.  N-Terminal Pro-B-Type Natriuretic Peptide Is a Major Predictor of the Development of Atrial Fibrillation: The Cardiovascular Health Study , 2009, Circulation.

[141]  A. Capucci,et al.  Presence and Duration of Atrial Fibrillation Detected by Continuous Monitoring: Crucial Implications for the Risk of Thromboembolic Events , 2009, Journal of cardiovascular electrophysiology.

[142]  R. Troughton,et al.  Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. , 2011, The New England journal of medicine.

[143]  A. Hofman,et al.  Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. , 2006, European heart journal.

[144]  James B Seward,et al.  Left ventricular diastolic dysfunction as a predictor of the first diagnosed nonvalvular atrial fibrillation in 840 elderly men and women. , 2002, Journal of the American College of Cardiology.

[145]  Robert Ploutz-Snyder,et al.  Mechanisms of Wave Fractionation at Boundaries of High-Frequency Excitation in the Posterior Left Atrium of the Isolated Sheep Heart During Atrial Fibrillation , 2006, Circulation.

[146]  Y. Ohashi,et al.  Alcohol consumption and risk of atrial fibrillation: a meta-analysis. , 2011, Journal of the American College of Cardiology.

[147]  J. Seward,et al.  Obesity as a risk factor for the progression of paroxysmal to permanent atrial fibrillation: a longitudinal cohort study of 21 years. , 2008, European heart journal.

[148]  J. Halperin,et al.  Transesophageal echocardiographic correlates of clinical risk of thromboembolism in nonvalvular atrial fibrillation. Stroke Prevention in Atrial Fibrillation III Investigators. , 1998, Journal of the American College of Cardiology.

[149]  真之 山田,et al.  St. Jude Medical弁置換術の遠隔成績 , 1991 .

[150]  Michel Haïssaguerre,et al.  Left Atrial Appendage Activity Translation in the Standard 12‐Lead ECG , 2011, Journal of cardiovascular electrophysiology.

[151]  N. Lakkis,et al.  Role of inflammation in initiation and perpetuation of atrial fibrillation: a systematic review of the published data. , 2007, Journal of the American College of Cardiology.

[152]  A. Baccarelli,et al.  Cardiovascular Epigenetics: Basic Concepts and Results From Animal and Human Studies , 2010, Circulation. Cardiovascular genetics.

[153]  Jeroen J. Bax,et al.  Comparison between tissue Doppler imaging and velocity-encoded magnetic resonance imaging for measurement of myocardial velocities, assessment of left ventricular dyssynchrony, and estimation of left ventricular filling pressures in patients with ischemic cardiomyopathy. , 2008, The American journal of cardiology.

[154]  H. Huikuri,et al.  Autonomic Dysfunction and New‐Onset Atrial Fibrillation in Patients With Left Ventricular Systolic Dysfunction After Acute Myocardial Infarction: A CARISMA Substudy , 2010, Journal of cardiovascular electrophysiology.

[155]  D. Singer,et al.  Impact of Proteinuria and Glomerular Filtration Rate on Risk of Thromboembolism in Atrial Fibrillation: The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study , 2009, Circulation.

[156]  S. Connolly,et al.  Analysis of Stroke in ATHENA: A Placebo-Controlled, Double-Blind, Parallel-Arm Trial to Assess the Efficacy of Dronedarone 400 mg BID for the Prevention of Cardiovascular Hospitalization or Death From Any Cause in Patients With Atrial Fibrillation/Atrial Flutter , 2009, Circulation.

[157]  Michael J Ackerman,et al.  Prevalence of early-onset atrial fibrillation in congenital long QT syndrome. , 2008, Heart rhythm.

[158]  Thomas Meitinger,et al.  Large scale replication and meta-analysis of variants on chromosome 4q25 associated with atrial fibrillation. , 2008, European heart journal.

[159]  S. Greenberg,et al.  Warfarin-associated hemorrhage and cerebral amyloid angiopathy , 2000, Neurology.

[160]  R. Melotti,et al.  Effect of coffee consumption, lifestyle and acute life stress in the development of acute lone atrial fibrillation , 2008, Journal of cardiovascular medicine.

[161]  E. Eaker,et al.  Anger and Hostility Predict the Development of Atrial Fibrillation in Men in the Framingham Offspring Study , 2004, Circulation.

[162]  E. Hylek,et al.  Future directions of stroke prevention in atrial fibrillation: the potential impact of novel anticoagulants and stroke risk stratification , 2011, Journal of thrombosis and haemostasis : JTH.

[163]  Frank Beckers,et al.  Cryptogenic Stroke and underlying Atrial Fibrillation (CRYSTAL AF): design and rationale. , 2010, American heart journal.

[164]  J. Brugada,et al.  Long-lasting sport practice and lone atrial fibrillation. , 2002, European heart journal.

[165]  I. V. Van Gelder,et al.  Gender-related differences in rhythm control treatment in persistent atrial fibrillation: data of the Rate Control Versus Electrical Cardioversion (RACE) study. , 2005, Journal of the American College of Cardiology.

[166]  M. Pfeffer,et al.  Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial , 2006, The Lancet.

[167]  M. Rubenfire,et al.  Predicting Atrial Fibrillation Recurrence With Circulating Inflammatory Markers in Patients in Sinus Rhythm at High Risk for Atrial Fibrillation : Data From the GISSI Atrial Fibrillation Trial , 2011 .

[168]  C. Albert,et al.  Influence of systolic and diastolic blood pressure on the risk of incident atrial fibrillation in women. , 2009, Circulation.

[169]  G. Breithardt,et al.  The Registry of the German Competence NETwork on Atrial Fibrillation: patient characteristics and initial management , 2008, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[170]  Susan Regan,et al.  Major Hemorrhage and Tolerability of Warfarin in the First Year of Therapy Among Elderly Patients With Atrial Fibrillation , 2007, Circulation.

[171]  Frank Edelmann,et al.  Enhanced Detection of Paroxysmal Atrial Fibrillation by Early and Prolonged Continuous Holter Monitoring in Patients With Cerebral Ischemia Presenting in Sinus Rhythm , 2010, Stroke.

[172]  Jun Zhu,et al.  Apixaban in patients with atrial fibrillation. , 2011, The New England journal of medicine.

[173]  R. Tieleman,et al.  Atrial tissue Doppler imaging for prediction of new-onset atrial fibrillation , 2008, Heart.

[174]  R. Thadhani,et al.  Warfarin use associates with increased risk for stroke in hemodialysis patients with atrial fibrillation. , 2009, Journal of the American Society of Nephrology : JASN.

[175]  Daniel Levy,et al.  Long-term outcomes in individuals with prolonged PR interval or first-degree atrioventricular block. , 2009, JAMA.

[176]  James B Seward,et al.  Prediction of cardiovascular outcomes with left atrial size: is volume superior to area or diameter? , 2006, Journal of the American College of Cardiology.

[177]  Jeroen J. Bax,et al.  Imaging and atrial fibrillation: the role of multimodality imaging in patient evaluation and management of atrial fibrillation. , 2010, European Heart Journal.

[178]  Matthew Wright,et al.  Catheter ablation for atrial fibrillation: are results maintained at 5 years of follow-up? , 2011, Journal of the American College of Cardiology.

[179]  D. Schwartzman,et al.  Genetic susceptibility to atrial fibrillation in patients with congestive heart failure. , 2006, Heart rhythm.

[180]  Gerhard Hindricks,et al.  Performance of a New Leadless Implantable Cardiac Monitor in Detecting and Quantifying Atrial Fibrillation Results of the XPECT Trial , 2010, Circulation. Arrhythmia and electrophysiology.

[181]  J. Manson,et al.  The long- and short-term impact of elevated body mass index on the risk of new atrial fibrillation the WHS (women's health study). , 2010, Journal of the American College of Cardiology.

[182]  Martin Borggrefe,et al.  Short QT Syndrome: A Familial Cause of Sudden Death , 2003, Circulation.

[183]  Stephan Willems,et al.  Early and comprehensive management of atrial fibrillation: executive summary of the proceedings from the 2nd AFNET-EHRA consensus conference 'research perspectives in AF'. , 2009, European heart journal.

[184]  G. Breithardt,et al.  Impact of the type of centre on management of AF patients: Surprising evidence for differences in antithrombotic therapy decisions , 2011, Thrombosis and Haemostasis.

[185]  A. Hofman,et al.  High-normal thyroid function and risk of atrial fibrillation: the Rotterdam study. , 2008, Archives of internal medicine.

[186]  K. Kario,et al.  Reduced Estimated Glomerular Filtration Rate Is Associated with Stroke Outcome after Intravenous rt-PA: The Stroke Acute Management with Urgent Risk-Factor Assessment and Improvement (SAMURAI) rt-PA Registry , 2010, Cerebrovascular Diseases.

[187]  J. Struck,et al.  Circulating cardiovascular biomarkers in recurrent atrial fibrillation: data from the GISSI‐Atrial Fibrillation Trial , 2011, Journal of internal medicine.

[188]  René M. Botnar,et al.  Right atrial scar detection after catheter ablation: Comparison of 2D and high spatial resolution 3D-late enhancement magnetic resonance imaging. , 2011, Academic radiology.

[189]  K. Rathgen,et al.  Influence of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Oral Dabigatran Etexilate , 2010, Clinical pharmacokinetics.

[190]  J. Brugada,et al.  Cardiac Arrhythmogenic Remodeling in a Rat Model of Long-Term Intensive Exercise Training , 2011, Circulation.

[191]  B. Nordestgaard,et al.  Does elevated C-reactive protein increase atrial fibrillation risk? A Mendelian randomization of 47,000 individuals from the general population. , 2010, Journal of the American College of Cardiology.

[192]  K. Furie,et al.  Apolipoprotein E genotype and the risk of recurrent lobar intracerebral hemorrhage. , 2000, The New England journal of medicine.

[193]  G. Lip,et al.  Characterisation and validity of inflammatory biomarkers in the prediction of post-operative atrial fibrillation in coronary artery disease patients , 2010, Thrombosis and Haemostasis.

[194]  David Cunnington,et al.  Prevalence of sleep disordered breathing in paroxysmal and persistent atrial fibrillation patients with normal left ventricular function. , 2008, European heart journal.

[195]  Satoko Nakamura,et al.  Chronic kidney disease as an independent risk factor for new-onset atrial fibrillation in hypertensive patients , 2010, Journal of hypertension.

[196]  K. Lunetta,et al.  The Relation of Genetic and Environmental Factors to Systemic Inflammatory Biomarker Concentrations , 2009, Circulation. Cardiovascular genetics.

[197]  A L Waldo,et al.  Single site radiofrequency catheter ablation of atrial fibrillation: studies guided by simultaneous multisite mapping in the canine sterile pericarditis model. , 2000, Journal of the American College of Cardiology.

[198]  Elsayed Z Soliman,et al.  Association of Chronic Kidney Disease With Atrial Fibrillation Among Adults in the United States: REasons for Geographic and Racial Differences in Stroke (REGARDS) Study , 2011, Circulation. Arrhythmia and electrophysiology.

[199]  Nancy R Cook,et al.  Relation of vigorous exercise to risk of atrial fibrillation. , 2009, The American journal of cardiology.

[200]  J. Dernellis,et al.  Relationship between C-reactive protein concentrations during glucocorticoid therapy and recurrent atrial fibrillation. , 2004, European heart journal.

[201]  Nicholas S Peters,et al.  Electrophysiological Abnormalities Occur Prior to the Development of Clinical Episodes of Atrial Fibrillation: Observations from Human Epicardial Mapping , 2008, Pacing and clinical electrophysiology : PACE.

[202]  J. Brugada,et al.  Long-term endurance sport practice increases the incidence of lone atrial fibrillation in men: a follow-up study. , 2008, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[203]  S. Connolly,et al.  Effect of dronedarone on cardiovascular events in atrial fibrillation. , 2009, The New England journal of medicine.

[204]  A. Naidech,et al.  Prior antiplatelet therapy and outcome following intracerebral hemorrhage A systematic review , 2010 .

[205]  Roger C Barr,et al.  Mechanism of origin of conduction disturbances in aging human atrial bundles: experimental and model study. , 2007, Heart rhythm.

[206]  Dongfeng Qi,et al.  The Relationship Between Daily Atrial Tachyarrhythmia Burden From Implantable Device Diagnostics and Stroke Risk: The TRENDS Study , 2009, Circulation. Arrhythmia and electrophysiology.

[207]  Christian Gieger,et al.  Genome-wide association study of PR interval , 2010, Nature Genetics.

[208]  Stephan Willems,et al.  Early and comprehensive management of atrial fibrillation: proceedings from the 2nd AFNET/EHRA consensus conference on atrial fibrillation entitled 'research perspectives in atrial fibrillation'. , 2009, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[209]  J. Mathew,et al.  A multicenter risk index for atrial fibrillation after cardiac surgery. , 2004, JAMA.

[210]  Wei Huang,et al.  KCNQ1 Gain-of-Function Mutation in Familial Atrial Fibrillation , 2003, Science.

[211]  G. Breithardt,et al.  Prolonged Atrial Action Potential Durations and Polymorphic Atrial Tachyarrhythmias in Patients with Long QT Syndrome , 2003, Journal of cardiovascular electrophysiology.

[212]  B. Lindsay,et al.  Noninvasive Characterization of Epicardial Activation in Humans With Diverse Atrial Fibrillation Patterns , 2010, Circulation.

[213]  J. Brugada,et al.  Endurance sport practice as a risk factor for atrial fibrillation and atrial flutter , 2008, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[214]  Yuchiao Chang,et al.  Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. , 2003, The New England journal of medicine.

[215]  G. Breithardt,et al.  Knock-in gain-of-function sodium channel mutation prolongs atrial action potentials and alters atrial vulnerability. , 2010, Heart rhythm.

[216]  C. Weinz,et al.  Pharmacokinetics of BAY 59-7939 – an oral, direct Factor Xa inhibitor – in rats and dogs , 2005, Xenobiotica; the fate of foreign compounds in biological systems.

[217]  J. Gardin,et al.  Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). , 1994, The American journal of cardiology.

[218]  Leora Peltz,et al.  Epicardial Mapping of Chronic Atrial Fibrillation in Patients: Preliminary Observations , 2004, Circulation.

[219]  D. Roden,et al.  Metabolic Syndrome and Risk of Development of Atrial Fibrillation: The Niigata Preventive Medicine Study , 2008, Circulation.

[220]  G. Lip,et al.  Female gender is a risk factor for stroke and thromboembolism in atrial fibrillation patients , 2009, Thrombosis and Haemostasis.

[221]  S. Yusuf,et al.  Benefit of Oral Anticoagulant Over Antiplatelet Therapy in Atrial Fibrillation Depends on the Quality of International Normalized Ratio Control Achieved by Centers and Countries as Measured by Time in Therapeutic Range , 2008, Circulation.

[222]  Ulrich Schotten,et al.  Electropathological Substrate of Long-Standing Persistent Atrial Fibrillation in Patients With Structural Heart Disease: Longitudinal Dissociation , 2010, Circulation. Arrhythmia and electrophysiology.

[223]  Fredrik Folke,et al.  Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. , 2010, Archives of internal medicine.

[224]  Dietrich Andresen,et al.  Atrial fibrillation management: a prospective survey in ESC member countries: the Euro Heart Survey on Atrial Fibrillation. , 2005, European heart journal.

[225]  D. Tamborero,et al.  Physical activity, height, and left atrial size are independent risk factors for lone atrial fibrillation in middle-aged healthy individuals. , 2008, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[226]  N. Cook,et al.  Alcohol consumption and risk of incident atrial fibrillation in women. , 2008, JAMA.

[227]  Lluís Mont,et al.  Fate of left atrial function as determined by real-time three-dimensional echocardiography study after radiofrequency catheter ablation for the treatment of atrial fibrillation. , 2008, The American journal of cardiology.

[228]  T. Lumley,et al.  Blood pressure control and risk of incident atrial fibrillation. , 2008, American journal of hypertension.

[229]  M. Allessie,et al.  Time course and mechanisms of endo-epicardial electrical dissociation during atrial fibrillation in the goat. , 2011, Cardiovascular research.

[230]  R. D'Agostino,et al.  Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. , 1994, The New England journal of medicine.

[231]  Olle Melander,et al.  Assessment of conventional cardiovascular risk factors and multiple biomarkers for the prediction of incident heart failure and atrial fibrillation. , 2010, Journal of the American College of Cardiology.

[232]  D. Levy,et al.  Pulse pressure and risk of new-onset atrial fibrillation. , 2007, JAMA.

[233]  P. Kirchhof,et al.  MRI of right atrial function after catheter ablation of atrial flutter. , 2010, Academic radiology.

[234]  Andreas Metzner,et al.  Long-Term Results of Catheter Ablation in Paroxysmal Atrial Fibrillation: Lessons From a 5-Year Follow-Up , 2010, Circulation.

[235]  J Clémenty,et al.  Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. , 1998, The New England journal of medicine.

[236]  C. Israel,et al.  Long-term risk of recurrent atrial fibrillation as documented by an implantable monitoring device: implications for optimal patient care. , 2004, Journal of the American College of Cardiology.