Risk Factors of Atrial Fibrillation and Outstanding Issues of Its Prevention


  • S.M. Koval State Institution «Institute of Therapy named after L.T. Mala of the National Academy of Medical Sciences of Ukraine», Kharkiv
  • I.O. Snigurska State Institution «Institute of Therapy named after L.T. Mala of the National Academy of Medical Sciences of Ukraine», Kharkiv




atrial fibrillation, risk factors, primary prevention, review


The article presents the main pathogenetic mecha­nisms of onset and progression of atrial fibrillation (AF). We analyzed the most common and important risk factors for its development. At the moment, the problem of AF prevention remains unsolved. First of all, we are talking about the primary prevention of AF. Primary prevention of AF is the most effective method for the control of this pathology, which will significantly reduce the incidence of AF, and because of this — the risk of complications and mortality. Unresolved problem of primary prevention of AF is associated with considerable complexity of its implementation. This is due to a very high prevalence and the large number of modifiable risk factors, as well as the presence of such non-modifiable risk factors, such as age and genetic predisposition.


Holytsyn SP, Panchenko EP, Popov SV. [Diagnosis and treatment of atrial fibrillation. Recommendations of the Russian Society of Cardiology]. Russian cardiology journal.2012;4 (102): 1-100. Russian.

Sыchev OS., Mykhaleva TV. [Non-valvular atrial fibrillation genesis in patients aged less than 65 years with preserved left ventricular systolic function: clinical features and myocardial remodeling ] Ukrainian cardiology journal. 2014;3:53-60. Ukrainian.

Sychov OS. Kovalenko VM., Dzyak HV. [Diagnostics and treatment of atrial fibrillation. Recommendations of the Working Group on arrhythmia of the Association of Cardiologists of Ukraine]. Kiev.2014; 167 p. Ukrainian.

Sыvolap VD., Lashkul DA., Marchenko VV. [Features of cardiac remodeling in patients with different clinical forms of non-valvular atrial fibrillation] ScienceRise. 2016;4 (3):32-38. Ukrainian.

Tatarskyy BA, Batalov RE, Popov SV [Atrial fibrillation: pathophysiological approach to the choice of antiarrhythmic therapy] Tomsk. 2013; 484 p. Russian.

Abed HS, Samuel CS, Lau DH, Kelly DJ, Royce SG, Alasady M, Mahajan R, Kuklik P, Zhang Y, Brooks AG, Nelson AJ, Worthley SG, Abhayaratna WP, Kalman JM, Wittert GA, Sanders P. Obesity results in progressive atrial structural and electrical remodeling: implications for atrial fibrillation. Heart Rhythm. 2013;10:90–100.

Aizer A, Gaziano JM, Cook NR, Manson JE, Buring JE, Albert CM. Relation of vigorous exercise to risk of atrial fibrillation. Am J Cardiol. 2009;103:1572–7.

Arnar DO, Thorvaldsson S, Manolio TA, Thorgeirsson G, Kristjansson K, Hakonarson H, Stefansson K. Familial aggregation of atrial fibrillation in Iceland. Eur Heart J. 2006; 27: 708–712.

Benjamin, EJ., Chen, PS, Bild, DE, Mascette A M. Prevention of atrial fibrillation report from a National Heart, Lung, and Blood Institute workshop.Circulation. 2009; 119 (4): 606-618.

Berti D, Moors E, Moons Ph, Heidbuche H. Prevalence and antithrombotic management of atrial fibrillation in hospitalised patients Heart. 2015;101:884-893

Bettoni M, Zimmermann M. Autonomic tone variations before the onset of paroxysmal atrial fibrillation. Circulation. 2002; 105:2753–2759.

Borzecki AM, Bridgers DK, Liebschutz JM, Kader B, Kazis LE, Berlowitz DR. Racial differences in the prevalence of atrial fibrillation among males. J Natl Med Assoc. 2008; 100: 237–245.

Burstein B, Qi XY, Yeh YH, Calderone A, Nattel S. Atrial cardiomyocyte tachycardia alters cardiac fibroblast function: a novel consideration in atrial remodeling. Cardiovasc Res. 2007; 76: 442–452.

Burstein B, Nattel S. Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation. J Am Coll Cardiol. 2008; 51: 802–809.

Calloe K, Ravn LS, Schmitt N, Sui JL, Duno M, Haunso S, Grunnet M, Svendsen JH, Olesen SP. Characterizations of a loss-of-function mutation in the Kir3.4 channel subunit. Biochem Biophys Res Commun. 2007; 364: 889–895.

Cappola AR, Fried LP, Arnold AM. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA 2006;295:1033–41.

Chen YC, Chen SA, Chen YJ. Effects of thyroid hormone on the arrhythmogenic activity of pulmonary vein cardiomyocytes. J Am Coll Cardiol. 2002;39:366–372.

Chen WJ, Yeh YH, Lin KH, Chang GJ, Kuo CT. Molecular characterization of thyroid hormone-inhibited atrial L-type calcium channel expression: implication for atrial fibrillation in hyperthyroidism.Basic Res Cardiol. 2011;106:163–174.

Chou CC, Nihei M, Zhou S, Tan A, Kawase A, Macias ES, Fishbein MC, Lin SF, Chen PS. Intracellular calcium dynamics and anisotropic reentry in isolated canine pulmonary veins and left atrium. Circulation. 2005; 111: 2889–2897.

Chung MK, Martin DO, Sprecher D, Wazni O, Kanderian A, Carnes CA, Bauer JA, Tchou PJ, Niebauer MJ, Natale A, Van Wagoner DR. C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation. 2001; 104: 2886–2891.

Clauss S., Ellinor P. T. Does Atrial Fibrillation Follow Function?: Ion Channel Mutations and Lone Atrial Fibrillation Circ Arrhythm Electrophysiol. 2015;8:1005-1006

Conen D, Tedrow UB, Koplan BA, Glynn RJ, BuringJE, Albert CM . Influence of systolic and diastolic blood pressure on the risk of incident atrial fibrillation in women.Circulation. 2009;119:2146–2152.

Copley DJ, Hill KM. Atrial Fibrillation: A Review of Treatments and Current Guidelines AACN Adv Crit Care. 2016;27:120-128.

Darbar D, Kannankeril PJ, Donahue BS, Kucera G, Stubblefield T, Haines JL, George AL Jr, Roden DM. Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation. Circulation.2008; 117: 1927–1935.

Djoussé L, Levy D, Benjamin EJ, Blease SJ, Russ A, Larson MG, Massaro JM, D'Agostino RB, Wolf PA, Ellison RC. Long-term alcohol consumption and the risk of atrial fibrillation in the Framingham Study.Am J Cardiol. 2004;93:710–713.

Ellinor PT, Yoerger DM, Ruskin JN, MacRae CA. Familial aggregation in lone atrial fibrillation. Hum Genet. 2005; 118: 179–184

Ellinor PT, MacRae CA. Ion channel mutations in AF: signal or noise? Heart Rhythm. 2008; 5: 436–437.

Ellinor PT . Genetics and molecular biology of AF. Circ Res.2014;114: 1453–1468.

Everett TH, Verheule S, Wilson EE, Foreman S, Olgin JE. Left atrial dilatation resulting from chronic mitral regurgitation decreases spatiotemporal organization of atrial fibrillation in left atrium. Am J Physiol. 2004; 286: H2452–H2460.

Everett TH, Olgin JE. Atrial fibrosis and the mechanisms of atrial fibrillation. Heart Rhythm. 2007; 4: S24–S27.

Fox CS, Parise H, D'Agostino RB, Sr., Lloyd-Jones DM, Vasan RS, Wang TJ, Levy D, Wolf PA, Benjamin EJ. Parental atrial fibrillation as a risk factor for atrial fibrillation in offspring. JAMA.2004; 291: 2851–2855.

Frost L, Vestergaard P . Alcohol and risk of atrial fibrillation or flutter: a cohort study. Arch Intern Med. 2004;164:1993–1998.

Frost L, Frost P, Vestergaard P. Work related physical activity and risk of a hospital discharge diagnosis of atrial fibrillation or flutter: the Danish Diet, Cancer, and Health Study. Occup Environ Med 2005; 62:49–53.

Gaborit N, Varro A, Le Bouter S. Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts. J Mol Cell Cardiol.2010;49:639–646.

Gami AS, Hodge DO, Herges RM, Olson EJ, Nykodym J, Kara T, Somers VK. Obstructive sleep apnea, obesity, and the risk of incident atrial fibrillation. J Am Coll Cardiol. 2007; 49: 565–571.

Ghezelbash S, Molina CE, DobrevD. Altered Atrial Metabolism: An Underappreciated Contributor to the Initiation and Progression of Atrial Fibrillation JAHA. 2015;4:e001808.

Gollob MH, Jones DL, Krahn AD, Danis L, Gong XQ, Shao Q, Liu X, Veinot JP, Tang AS, Stewart AF, Tesson F, Klein GJ, Yee R, Skanes AC, Guiraudon GM, Ebihara L, Bai D. Somatic mutations in the connexin 40 gene (GJA5) in atrial fibrillation. N Engl J Med.2006; 354: 2677–2688.

Grundvold I, Skretteberg PT, Liestol K, Erikssen G, Kjeldsen SE, Arnesen H, Erikssen J, Bodegard J Upper normal blood pressures predict incident atrial fibrillation in healthy middle-aged men: a 35-year follow-up study.Hypertension. 2012;59:198–204.

Guasch E, Benito B, Qi X, Cifelli C, Naud P, Shi Y, Mighiu A, Tardif JC, Tadevosyan A, Chen Y, Gillis MA, Iwasaki YK, Dobrev D, Mont L, Heximer S, Nattel S Atrial fibrillation promotion by endurance exercise: demonstration and mechanistic exploration in an animal model. J Am Coll Cardiol. 2013;62:68–77.

Gudbjartsson DF, Arnar DO, Helgadottir A, Gretarsdottir S, Holm H, Sigurdsson A, Jonasdottir A, Baker A, Thorleifsson G, Kristjansson K, Palsson A, Blondal T, Sulem P, Backman VM, Hardarson GA, Palsdottir E, Helgason A, Sigurjonsdottir R, Sverrisson JT, Kostulas K, Ng MC, Baum L, So WY, Wong KS, Chan JC, Furie KL, Greenberg SM, Sale M, Kelly P, MacRae CA, Smith EE, Rosand J, Hillert J, Ma RC, Ellinor PT, Thorgeirsson G, Gulcher JR, Kong A, Thorsteinsdottir U, Stefansson K. Variants conferring risk of atrial fibrillation on chromosome 4q25. Nature.2007; 448: 353–357.

Hayashi H, Wang C, Miyauchi Y, Omichi C, Pak HN, Zhou S, Ohara T, Mandel WJ, Lin SF, Fishbein MC, Chen PS, Karagueuzian HS. Aging-related increase to inducible atrial fibrillation in the rat model. J Cardiovasc Electrophysiol. 2002; 13: 801–808.

Healey JS, Baranchuk A, Crystal E, Morillo CA, Garfinkle M, Yusuf S, Connolly SJ. Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis. Journal of the American College of Cardiology.2005; 45(11), 1832-1839.

Heeringa J, Van Der Kuip DA, Hofman A, Kors JA, van Herpen G, Stricker BH, Stijnen T, Lip GY, Witteman JC. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam Study.Eur Heart J. 2006; 27: 949–953.

Heijman J, Voigt N, Nattel S, Dobrev D. Cellular and Molecular Electrophysiology of Atrial Fibrillation Initiation, Maintenance, and Progression Circ. Res.. 2014;114:1483-1499.

Heijman J, Algalarrondo V, Voigt N, Melka J, Wehrens XH, Dobrev D, Nattel S. The value of basic research insights into atrial fibrillation mechanisms as a guide to therapeutic innovation: a critical analysis Cardiovasc Res. 2016;109:467-479

Hong K., Xiong Q.Genetic basis of atrial fibrillation // Curr. Opin. Cardiol.– 2014.– Vol. 29.– P. 220–226.

Issac TT, Dokainish H, Lakkis NM. Role of inflammation in initiation and perpetuation of atrial fibrillation: a systematic review of the published data. J Am Coll Cardiol. 2007; 50: 2021–2028.

Iwasaki YK, Shi Y, Benito B, Gillis MA, Mizuno K, Tardif JC, Nattel S. Determinants of atrial fibrillation in an animal model of obesity and acute obstructive sleep apnea. Heart Rhythm. 2012;9:1409–16.e1.

Iwasaki YK, Shi YF, Kato T. Repetitive obstructive sleep apnea produces cardiac remodeling and a substrate for atrial fibrillation. Heart Rhythm. 2012;9:S189–S19.

January C., Wann L., Alpert J. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. 2014; Vol. 129.

Kalifa J, Jalife J, Zaitsev AV, Bagwe S, Warren M, Moreno J, Berenfeld O, Nattel S. Intra-atrial pressure increases rate and organization of waves emanating from the superior pulmonary veins during atrial fibrillation. Circulation. 2003; 108: 668–671.

Kirchhof P., Breithardt G., Aliot E. Personalized management of atrial fibrillation: Proceedings from the fourth Atrial Fibrillation competence NETwork. European Heart Rhythm Association consensus conference . Europace.2013; 15: 1540–1556.

Kodama S, Saito K, Tanaka S. Alcohol consumption and risk of atrial fibrillation: a meta-analysis. J Am Coll Cardiol 2011;57:427–36.

Koektuerk B, Aksoy M, Horlitz M, Bozdag-Turan I, Goekmen Turan R. Role of diabetes in heart rhythm disorders. World J Diabetes. 2016 Feb 10; 7(3): 45–49.

Koura T, Hara M, Takeuchi S, Ota K, Okada Y, Miyoshi S, Watanabe A, Shiraiwa K, Mitamura H, Kodama I , Ogawa S.Anisotropic conduction properties in canine atria analyzed by high-resolution optical mapping: preferential direction of conduction block changes from longitudinal to transverse with increasing age. Circulation.2002;105:2092–2098.

Lau DH, Mackenzie L, Kelly DJ. Hypertension and atrial fibrillation: evidence of progressive atrial remodeling with electrostructural correlate in a conscious chronically instrumented ovine model. Heart Rhythm. 2010;7:1282–1290.

Lemoine MD, Duverger JE, Naud P, Chartier D., Qi XY. Arrhythmogenic left atrial cellular electrophysiology in a murine genetic long QT syndrome model. Cardiovasc Res. 2011;92:67–74.

Leong-Sit P., Zado E., Callans DJ, Garcia F, Lin D, Dixit S, Bala R, Riley MP, Hutchinson MD, Cooper J, Gerstenfeld EP, Marchlinski FE. Efficacy and risk of atrial fibrillation ablation before 45 years of age. Circ. Arrhythm. Electrophysiol. 2010; 3 (5):452–457.

Liew R. Almanac 2013: cardiac arrhythmias and pacing. Heart.2013; 99 (19): 1398–1407.

Li D, Fareh S, Leung TK, Nattel S. Promotion of atrial fibrillation by heart failure in dogs: atrial remodeling of a different sort.Circulation. 1999; 100: 87–95.

Li N., Dobrev D., Wehrens X. H. PITX2: a master regulator of cardiac channelopathy in atrial fibrillation?Cardiovasc Res. 2016;109:345-347,

Liu XK, Jahangir A, Terzic A, Gersh, B.J., Hammill, S.C., Shen, W.K. Age- and sex-related atrial electrophysiologic and structural changes. Am J Cardiol. 2004;94:373–375.

Liu T, Korantzopoulos P, Shao Q, Zhang Z, Letsas KP, Li G Mineralocorticoid receptor antagonists and atrial fibrillation: a meta-analysis, Europace. 2016 May;18(5):672-8

34. Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, D'Agostino RB, Massaro JM, Beiser A, Wolf PA, Benjamin EJ. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004; 110: 1042–1046.

London B, Albert C, Anderson ME, Giles WR, Van Wagoner DR, Balk E, Billman GE, Chung M, Lands W, Leaf A, McAnulty J, Martens JR, Costello RB, Lathrop DA. Omega-3 fatty acids and cardiac arrhythmias: prior studies and recommendations for future research: a report from the National Heart, Lung, and Blood Institute and Office of Dietary Supplements Omega-3 Fatty Acids and Their Role in Cardiac Arrhythmogenesis Workshop. Circulation. 2007;116: e320–e335.

Lubitz SA, Ozcan C, Magnani JW. Genetics of atrial fibrillation: implications for future research directions and personalized medicine. Circ Arrhythm Electrophysiol.2010;3:291–299.

Lundby A, Ravn LS, Svendsen JH, Hauns S, Olesen SP, Schmitt N. KCNE3 mutation V17M identified in a patient with lone atrial fibrillation. Cell Physiol Biochem. 2008; 21: 47–54.

Macheret F, Bartz TM, Djousse L, Ix JH, Mukamal KJ, Zieman SJ, Siscovick DS, Tracy RP, Heckbert SR, Psaty BM, Kizer JR. Higher circulating adiponectin levels are associated with increased risk of atrial fibrillation in older adults//Heart 2015;101:1368-1374.

Mathew JP, Fontes ML, Tudor IC, Ramsay J, Duke P, Mazer CD, Barash PG, Hsu PH, Mangano DT. A multicenter risk index for atrial fibrillation after cardiac surgery. JAMA 2004;291:1720–9.

Mont L, Sambola A, Brugada J, Vacca M, Marrugat J, Elosua R, Paré C, Azqueta M, Sanz G. Long-lasting sport practice and lone atrial fibrillation. Eur Heart J 2002;23:477–82.

Nattel S, Shiroshita-Takeshita A, Brundel BJ, Rivard L. Mechanisms of atrial fibrillation: lessons from animal models. Prog Cardiovasc Dis. 2005; 48: 9–28.

Nattel S, Maguy A, Le Bouter S, Yeh YH. Arrhythmogenic ion-channel remodeling in the heart: heart failure, myocardial infarction, and atrial fibrillation. Physiol Rev. 2007; 87: 425–456.

Nattel S, Dobrev D. Deciphering the fundamental mechanisms of atrial fibrillation: a quest for over a century Cardiovasc Res. 2016;109:465-466

Naruse Y, Tada H, Satoh M, Yanagihara M. Concomitant obstructive sleep apnea increases the recurrence of atrial fibrillation following radiofrequency catheter ablation of atrial fibrillation: clinical impact of continuous positive airway pressure therapy. Heart Rhythm.2013;10:331–337

Nishida K, Qi XY, Wakili R. Mechanisms of atrial tachyarrhythmias associated with coronary artery occlusion in a chronic canine model. Circulation.2011;123:137–146.

Novaro GM, Asher CR, Bhatt DL, Moliterno DJ, Harrington RA, Lincoff AM, Newby LK, Tcheng JE, Hsu AP, Pinski SL. Meta-analysis comparing reported frequency of atrial fibrillation after acute coronary syndromes in Asians versus whites. Am J Cardiol.2008; 101: 506–509.

Ogawa M, Zhou S, Tan AY, Song J, Gholmieh G, Fishbein MC, Luo H, Siegel RJ, Karagueuzian HS, Chen LS, Lin SF, Chen PS. Left stellate ganglion and vagal nerve activity and cardiac arrhythmias in ambulatory dogs with pacing-induced congestive heart failure. J Am Coll Cardiol. 2007; 50: 335–343.

Okin PM, Wachtell K, Devereux RB, Harris KE, Jern S, Kjeldsen SE, Julius S, Lindholm LH, Nieminen MS, Edelman JM, Hille DA, Dahlof B. Regression of electrocardiographic left ventricular hypertrophy and decreased incidence of new-onset atrial fibrillation in patients with hypertension. JAMA. 2006; 296: 1242–1248.

Olson TM, Michels VV, Ballew JD, Reyna SP, Karst ML, Herron KJ, Horton SC, Rodeheffer RJ, Anderson JL. Sodium channel mutations and susceptibility to heart failure and atrial fibrillation. JAMA. 2005; 293: 447–454.

Olson TM, Alekseev AE, Liu XK, Park S, Zingman LV, Bienengraeber M, Sattiraju S, Ballew JD, Jahangir A, Terzic A. Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human atrial fibrillation. Hum Mol Genet. 2006; 15: 2185–2191.

Ono N, Hayashi H, Kawase A, Lin SF, Li H, Weiss JN, Chen PS, Karagueuzian HS. Spontaneous atrial fibrillation initiated by triggered activity near the pulmonary veins in aged rats subjected to glycolytic inhibition. Am J Physiol. 2007; 292: H639–H648.

Otake H, Suzuki H, Honda T, Maruyama Y . Influences of autonomic nervous system on atrial arrhythmogenic substrates and the incidence of atrial fibrillation in diabetic heart. Int Heart J.2009;50:627–641.

Ravn LS, Aizawa Y, Pollevick GD, Hofman-Bang J, Cordeiro JM, Dixen U, Jensen G, Wu Y, Burashnikov E, Haunso S, Guerchicoff A, Hu D, Svendsen JH, Christiansen M, Antzelevitch C. Gain of function in IKs secondary to a mutation in KCNE5 associated with atrial fibrillation. Heart Rhythm. 2008; 5: 427–435.

Samokhvalov AV, Irving HM. Rehm J. Alcohol Consumption as a Risk Factor for Atrial Fibrillation: a Systematic Review and Meta-Analysis Eur J Cardiovasc Prev Rehabil. 2010 Dec; 17(6): 706–712.

Shan H, Zhang Y, Lu Y. Downregulation of miR-133 and miR-590 contributes to nicotine-induced atrial remodelling in canines. Cardiovasc Res. 2009;83:465–472.

Shan J, Xie W, Betzenhauser M. Calcium leak through ryanodine receptors leads to atrial fibrillation in 3 mouse models of catecholaminergic polymorphic ventricular tachycardia. Circ Res. 2012;111:708–717.

Sinno H, Derakhchan K, Libersan D, Yahye Merhi Y, Leung TK, ; Nattel Sl. Atrial ischemia promotes atrial fibrillation in dogs. Circulation.2003;107:1930–1936.

Tan AY, Zhou S, Ogawa M, Song J, Chu M, Li H, Fishbein MC, Lin SF, Chen LS, Chen PS. Neural mechanisms of paroxysmal atrial fibrillation and paroxysmal atrial tachycardia in ambulatory canines.Circulation. 2008; 118: 916–925.

Tanaka K, Zlochiver S, Vikstrom KL, Yamazaki M, Moreno J, Klos M, Zaitsev AV, Vaidyanathan R, Auerbach DS, Landas S, Guiraudon G, Jalife J, Berenfeld O, Kalifa J. Spatial distribution of fibrosis governs fibrillation wave dynamics in the posterior left atrium during heart failure. Circ Res. 2007 Oct 12;101(8):839-47.

Tran D.T.T., Perry, J.J., Dupuis, J.Y. Predicting new-onset postoperative atrial fibrillation in cardiac surgery patients.Journal of cardiothoracic and vascular anesthesia. 2015; 29 (5):1117-1126.

Tucker N. R., Clauss S., Ellinor P. T. Common variation in atrial fibrillation: navigating the path from genetic association to mechanism. Cardiovascular Research.2016; 109, 493–501.

Vaquero M, Calvo D, Jalife J. Cardiac fibrillation: from ion channels to rotors in the human heart. Heart Rhythm. 2008; 5: 872–879.

Verheule S, Sato T, Everett T, Engle SK, Otten D, Rubart-von der LM, Nakajima HO, Nakajima H, Field LJ, Olgin JE. Increased vulnerability to atrial fibrillation in transgenic mice with selective atrial fibrosis caused by overexpression of TGF-beta1. Circ Res.2004; 94: 1458–1465.

Verheule S, Wilson E, Everett T, Shanbhag S, Golden C, Jeffrey Olgin J. Alterations in atrial electrophysiology and tissue structure in a canine model of chronic atrial dilatation due to mitral regurgitation.Circulation. 2003;107:2615–2622.

Verheule S, Wilson E, Banthia S, Everett TH, Shanbhag S, Sih HJ, Olgin J. Direction-dependent conduction abnormalities in a canine model of atrial fibrillation due to chronic atrial dilatation. Am J Physiol. 2004; 287: H634–H644.

Wakili R, Voigt N, Kääb S,Dobrev D, Nattel S. Recent advances in the molecular pathophysiology of atrial fibrillation. J Clin Invest.2011;121:2955–2968.

Workman AJ, Kane KA, Rankin AC. The contribution of ionic currents to changes in refractoriness of human atrial myocytes associated with chronic atrial fibrillation. Cardiovasc Res. 2001; 52:226–235.

Workman AJ, Kane KA, Rankin AC. Characterisation of the Na, K pump current in atrial cells from patients with and without chronic atrial fibrillation. Cardiovasc Res. 2003; 59: 593–602.

Xia M, Jin Q, Bendahhou S, He Y, Larroque MM, Chen Y, Zhou Q, Yang Y, Liu Y, Liu B, Zhu Q, Zhou Y, Lin J, Liang B, Li L, Dong X, Pan Z, Wang R, Wan H, Qiu W, Xu W, Eurlings P, Barhanin J, Chen Y. A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation. Biochem Biophys Res Commun. 2005; 332: 1012–1019.

Xiao P, Gao C, Fan J, et al. Blockade of angiotensin II improves hyperthyroid induced abnormal atrial electrophysiological properties. Regul Pept. 2011;169:31–38.

Yang Y, Xia M, Jin Q, Bendahhou S, Shi J, Chen Y, Liang B, Lin J, Liu Y, Liu B, Zhou Q, Zhang D, Wang R, Ma N, Su X, Niu K, Pei Y, Xu W, Chen Z, Wan H, Cui J, Barhanin J, Chen Y. Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation. Am J Hum Genet. 2004; 75: 899–905.

Yeh YH, Wakili R, Qi XY. Calcium-handling abnormalities underlying atrial arrhythmogenesis and contractile dysfunction in dogs with congestive heart failure. Circ Arrhythm Electrophysiol.2008;1:93–102.

Zhabyeyev P, Hiess F, Wang R. S4153R is a gain-of-function mutation in the cardiac Ca(2+) release channel ryanodine receptor associated with catecholaminergic polymorphic ventricular tachycardia and paroxysmal atrial fibrillation.Can J Cardiol. 2013;29:993–996.