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Aging and disease    2016, Vol. 7 Issue (5) : 635-656     DOI: 10.14336/AD.2016.0211
Review Article |
Atrial Fibrillation: The Science behind Its Defiance
Czick Maureen E.1, Shapter Christine L.2, Silverman David I.3
1Department of Anesthesiology,
2Department of Psychiatry, Hartford Hospital/Institute of Living, and
3Echocardiography Laboratory, Hartford Hospital, Hartford, CT 06106, USA.
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Atrial fibrillation (AF) is the most prevalent arrhythmia in the world, due both to its tenacious treatment resistance, and to the tremendous number of risk factors that set the stage for the atria to fibrillate. Cardiopulmonary, behavioral, and psychological risk factors generate electrical and structural alterations of the atria that promote reentry and wavebreak. These culminate in fibrillation once atrial ectopic beats set the arrhythmia process in motion. There is growing evidence that chronic stress can physically alter the emotion centers of the limbic system, changing their input to the hypothalamic-limbic-autonomic network that regulates autonomic outflow. This leads to imbalance of the parasympathetic and sympathetic nervous systems, most often in favor of sympathetic overactivation. Autonomic imbalance acts as a driving force behind the atrial ectopy and reentry that promote AF. Careful study of AF pathophysiology can illuminate the means that enable AF to elude both pharmacological control and surgical cure, by revealing ways in which antiarrhythmic drugs and surgical and ablation procedures may paradoxically promote fibrillation. Understanding AF pathophysiology can also help clarify the mechanisms by which emerging modalities aiming to correct autonomic imbalance, such as renal sympathetic denervation, may offer potential to better control this arrhythmia. Finally, growing evidence supports lifestyle modification approaches as adjuncts to improve AF control.

Keywords atrial fibrillation      pathophysiology      catheter ablation      surgical maze procedure      antiarrhythmic drugs      autonomic imbalance     
Corresponding Authors: Czick Maureen E.   
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These authors contributed equally to this work

Issue Date: 01 October 2016
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Czick Maureen E.
Shapter Christine L.
Silverman David I.
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Czick Maureen E.,Shapter Christine L.,Silverman David I.. Atrial Fibrillation: The Science behind Its Defiance[J]. Aging and disease, 2016, 7(5): 635-656.
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Figure 1.  Atrial Action Potential Ion Currents. While the SA cells are depolarizing, the surrounding contractile cells of the atria are at their resting membrane potential of approximately -90mV, due to the IK1 current. Once the SA depolarizes, it promptly passes depolarizing positive ions to the atrial cells through low resistance gap junction channels. These positive ions bring the atrial cells to their own threshold potential, opening voltage-gated sodium channels (INa) in the atrial cell membranes, so that the atrial cells fire their own action potentials. At the peak of the upstroke in the atria, transient outward (Ito) potassium channels open; positively-charged potassium ions exit the cell, beginning the process of repolarization. Their attempt to repolarize the atrial cells is short-lived however, because inward calcium current, conducted through voltage-gated L-type calcium channels (Ica(L)) keeps the cells in a state of depolarization just a bit longer, depicted as a plateau in the middle of the action potential waveform. The SA action potential does not need a calcium-based plateau current because SA cells are not responsible for contracting. Atrial cells, on the other hand, use the electrical depolarization from the action potential as the signal to contract. The “trigger” calcium entry through L-type channels during the plateau acts as a bridge between the electrical depolarization and mechanical contraction. The L-type channels inactivate rapidly, calcium current ceases, and then potassium exit, through multiple channels including the “ultra-rapid”-opening IKur, the “rapid” opening IKr (also called hERG channels) and the “slowly” opening IKs channels, fully repolarizes the cells.
Figure 2.  Sinoatrial Node Depolarization. Under normal conditions, the heart’s electrical rhythm is generated by the cells of the sinoatrial (SA) node. At the beginning of each cardiac cycle the membrane potential of the SA cells is approximately -60 mV, with the interior of the SA cells negatively charged relative to the cell exterior. Unlike contractile cardiac cells, SA cells do not have a stable resting membrane potential, so they remain poised at -60 for just the briefest moment, because “funny channels” (If) promptly spring open, allowing positively charged ions to leak from the extracellular space into the interior of the SA cells. As positive ions enter, the SA cell interiors become progressively less negatively charged (depolarized). The funny channel leak current (soon joined by Ca2+ current through T- and L-type channels, ICa(T), ICa(L)) -- and the change in the membrane potential that results from it -- is represented in the graph of the SA node action potential as the diagonal upslope at the start of action potential waveform, also referred to as “phase 4.” The positive ion influx quickly brings the SA cells toward the “threshold potential,” at approximately -40 mV, at which point voltage-gated calcium channels suddenly open, enabling a sudden massive surge of positive charge entry into the cell. This is the upstroke of the SA action potential, also called “phase 0.” Following the upstroke, there is an exodus of positively-charged potassium ions (IK) which restores the cell interior to its original negatively-charged baseline electrical potential during phase 3 repolarization.
[1] Arora R, (2012). Recent insights into the role of the autonomic nervous system in the creation of substrate for atrial fibrillation: implications for therapies targeting the atrial autonomic nervous system. Circ Arrh Electrophysiology, 5: 850-859
[2] Iwasaki Y, Nishida K, Kato T, Nattel S, (2011). Atrial fibrillation pathophysiology: implications for management. Circulation, 124: 2264-2274
[3] Menezes AR, Lavie CJ, DiNicolantonio JJ, O’Keefe J, Morin DP, Khatib S, et al. (2013). Atrial Fibrillation in the 21st Century: A Current Understanding of Risk Factors and Primary Prevention Strategies. Mayo Clinic Proceedings, 88: 394-409
[4] Kong MH, Lopes RD, Piccini JP, Hasselblad V, Bahnson TD, Al-Khatib SM, (2010). Surgical maze procedure as a treatment for atrial fibrillation: a meta-analysis of randomized controlled trials. Cardiovascular Therapeutics, 28: 311-326
[5] Chugh SS, Havmoeller R, Narayanan K, Singh D, Rienstra M, Benjamin EJ, et al. (2014). Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation, 129: 837-847
[6] Go AS, Hylek EM, Philips KA, Chang Y, Henault LE, Selby JV, et al. (2001). Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA, 285: 2370-2375
[7] Naccarelli GV, Varker H, Lin J, Schulman KL, (2009). Increasing prevalence of atrial fibrillation in the United States. Am J Cardiol, 104: 1534-1539
[8] Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Abhayaratna WP, et al. (2006). Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation, 114: 119-125
[9] Coromilas J, (2004) Obesity and atrial fibrillation: is one epidemic feeding the other? JAMA, 292: 2519
[10] Furberg CD, Psaty BM, Manolio TA, Gardin JM, Smith VE, Rautaharhu PM, (1994). Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). Am J Cardiol, 74: 236-241
[11] Villareal RP, Woodruff AL, Massumi A, (2001). Gender and cardiac arrhythmias. Texas Heart Institute Journal, 28: 265-275
[12] Yarnoz MJ, Curtis AB, (2008). More reasons why men and women are not the same (gender differences in electrophysiology and arrhythmias). Am J Cardiol, 101: 1291-1296
[13] Thomas K, Piccini JP, Liang L, Fonarow GC, Yancy CW, Peterson ED, et al. (2013). Racial differences in the prevalence and outcomes of atrial fibrillation among patients hospitalized with heart failure. Journal of the American Heart Association, 2: e000200
[14] Fatkin D, Otway R, Vandenberg JI, (2007). Genes and atrial fibrillation: A new look at an old problem. Circulation, 116: 782-792
[15] Lubitz SA, Ozcan C, Magnani JW, Kaab S, Benjamin ES, Ellinor PT, (2010). Genetics of atrial fibrillation: Implications for future research directions and personalized medicine. Circ Arrhythm Electrophysiol, 3: 291-299
[16] Tucker NR, Ellinor PT, (2014). Emerging directions in the genetics of atrial fibrillation. Circ Res, 114: 1469-1482
[17] Calvo N, Brugada J, Sitges M, Mont L, (2012). Atrial fibrillation and atrial flutter in athletes. Br J Sports Med, 46 Suppl 1: i37-i43
[18] Lau Y-F, Yiu K-H, Siu CW, Tse H-F, (2012). Hypertension and atrial fibrillation: epidemiology, pathophysiology and therapeutic implications. J Hum Hypertens, 26: 563-569
[19] Verdecchia P, Reboldi G, Gattobigio R, Bentivoglio M, Borgioni C, Angeli F, et al. (2003). Atrial fibrillation in hypertension: predictors and outcome. Hypertension, 41: 218-223
[20] Bunch TJ, Packer DL, Jahangir A, Locke GR, Talley NJ, Gersh BJ, et al. (2008). Long-term risk of atrial fibrillation with symptomatic gastroesophageal reflux disease and esophagitis. Am J Cardiol, 102: 1207-1211
[21] Chan WL, Yang KP, Chao TF, Huang CC, Huang PH, Chen YC, et al. (2014). The association of asthma and atrial fibrillation: a nationwide population-based nested case-control study. Int J Cardiol, 176: 464-469
[22] Warnier MJ, Rutten FH, Kors JA, Lammers JW, de Boer A, Hoes AW, et al. (2012). Cardiac arrhythmias in adult patients with asthma. J Asthma, 49: 942-946
[23] Sekine Y, Kesler KA, Behnia M, Brooks-Brunn J, Sekine E, Brown JW, (2001). COPD may increase the incidence of refractory supraventricular arrhythmias following pulmonary resection for non-small cell lung cancer. Chest, 120: 1783-1790
[24] Vretzakis G, Simeoforidou M, Stamoulis K, Bareka M, (2013). Supraventricular arrhythmias after thoracotomy: is there a role for autonomic imbalance? Anesthesiology Research and Practice, 2013: 413985
[25] Abbott KC, Trespalacios FC, Taylor AJ, Agodoa LY, (2003). Atrial fibrillation in chronic dialysis patients in the United States: risk factors for hospitalization and mortality. BMC Nephrology, 4: 1
[26] Atta MG, (2011). Atrial fibrillation in dialysis patients: a neglected comorbidity. J Am Soc Nephrol, 22: 203-205
[27] Zebe H, (2000). Atrial fibrillation in dialysis patients. Nephrol Dial Transplant, 15: 765-768
[28] Dublin S, Glazer NL, Smith NL, Psaty BM, Lumley T, Wiggins KL, et al (2010). Diabetes mellitus, glycemic control, and risk of atrial fibrillation. J Gen Intern Med, 25: 853-858
[29] Patel D, McConkey ND, Sohaney R, McNeil A, Jedrzejczyk A, Armaganijan L, (2013). A systematic review of depression and anxiety in patients with atrial fibrillation: the heart-mind link. Cardiovasc Psychiatry Neurol, 2013: 158850
[30] Grigioni F, Avierinos JF, Ling LH, Scott CG, Bailey KR, Tajik AJ et al. (2002). Atrial fibrillation complicating the course of degenerative mitral regurgitation. J Am Coll Cardiol, 40: 84-92
[31] Keren G, Etzion T, Sherez J, Zelcer AA, Megidish R, Miller HI, et al. (1987). Atrial fibrillation and atrial enlargement in patients with mitral stenosis. Am Heart J, 114: 1146-1155
[32] Probst P, Goldschlager N, Selzer A, (1973). Left atrial size and atrial fibrillation in mitral stenosis: factors influencing their relationship. Circulation, 48: 1282-1287
[33] N J, Francis J, (2005). Atrial fibrillation and hyperthyroidism. Indian Pacing and Electrophysiol J, 5: 305-311
[34] Mariscalco G, Klersy C, Zanobini M, Banach M, Ferrarese S, Borsani P, et al. (2008) Atrial fibrillation after isolated coronary surgery affects late survival. Circulation, 118: 1612
[35] Mathew JP, Fontes ML, Tudor IC, Ramsay J, Duke P, Mazer CD, et al. (2004). A multicenter risk index for atrial fibrillation after cardiac surgery. JAMA, 291: 1720-1729
[36] Echahidi N, Pibarot P, O’Hara G, Mathieu P, (2008). Mechanisms, prevention, and treatment of atrial fibrillation after cardiac surgery. J Am Coll Cardiol, 51: 793-801
[37] Gomez-Caro A, Moradiellos FJ, Ausin P, Diaz-Hellin V, Larru E, Perez-Anton JA, et al. (2006). Risk factors for atrial fibrillation after thoracic surgery. Arch Bronchoneumol, 42: 9-13
[38] Wanahita N, Messerli FH, Bangalore S, Gami AS, Somers VK, Steinberg JS, (2008). Atrial fibrillation and obesity--results of a meta-analysis. Am Heart J, 155: 310-315
[39] Asirvatham SJ, Kapa S, (2009). Sleep apnea and atrial fibrillation: the autonomic link. J Am Coll Cardiol, 54: 2084-2086
[40] Gami AS, Pressman G, Caples SM, Kanagala R, Gard JJ, Davison DE, et al. (2004). Association of atrial fibrillation and obstructive sleep apnea. Circulation, 110: 364-367
[41] Monahan D, Redline S, (2011). Role of obstructive sleep apnea in cardiovascular disease. Curr Opin Cardiol, 26: 541-547
[42] Hansson A, Madsen-Hardig B, Olsson SB, (2004). Arrhythmia-provoking factors and symptoms at the onset of paroxysmal atrial fibrillation: a study based on interviews with 100 patients seeking hospital assistance. BMC Cardiovasc Disord, 4: 13
[43] Mandyam MC, Vedantham V, Scheinman MM, Tseng ZH, Badhwar N, Lee BK, et al. (2012). Alcohol and Vagal Tone as Triggers for Paroxysmal Atrial Fibrillation. Am J Cardiol, 110: 364-368
[44] Heeringa J, Kors JA, Hofman A, van Rooij FJ, Witteman JC, (2008). Cigarette smoking and risk of atrial fibrillation: the Rotterdam study. Am Heart J, 156: 1163-1169
[45] Krijthe BP, Heeringa J, Hofman A, Franco OH, Stricker BH, (2014). Non-steroidal anti-inflammatory drugs and the risk of atrial fibrillation: a population-based follow-up study. BMJ Open, 4: e004059
[46] Varriale P, Ramaprasad S, (1993). Aminophylline induced atrial fibrillation. Pacing Clin Elextrophysiol, 16: 1953-1955
[47] Shen J, Johnson VM, Sullivan LM, Jacques PF, Magnani JW, Lubitz SA, et al. (2011). Dietary factors and incident atrial fibrillation: the Framingham Heart Study. Am J Clin Nutr, 93: 261-266
[48] Conen D, Chiuve SE, Everett BM, Zhang SM, Buring JE, Albert CM, (2010). Caffeine consumption and incident atrial fibrillation in women. Am J Clin Nutr, 92: 509-514
[49] Bhave PD, Hoffmayer K, (2013). Caffeine and atrial fibrillation: friends or foes? Heart, 99: 1377-1378
[50] Caldeira D, Martins C, Alves LB, Pereira H, Ferreira JJ, Costa J, (2013). Caffeine does not increase the risk of atrial fibrillation: a systematic review and meta-analysis of observational studies. Heart, 99: 1383-1389
[51] Kozlowski D, Budrejko S, Lip GY, Rysz J, Mikhailidis DP, Raczak G, et al. (2010). Lone atrial fibrillation: what do we know? Heart, 96: 498-503
[52] Wakili R, Voigt N, Kaab S, Dobrev D, Nattel S, (2011). Recent advances in the molecular pathophysiology of atrial fibrillation. J Clin Invest, 121: 2955-2968
[53] Nattel S, (2002). New ideas about atrial fibrillation 50 years on. Nature, 415: 219-226
[54] Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, et al. (2011). Heart disease and stroke statistics-2011 update: a report from the American Heart Association. Circulation, 123: e18-e209
[55] Benjamin EJ, Chen PS, Bild DE, Mascette AM, Albert CM, Alonso A, et al. (2009). Prevention of atrial fibrillation: Report from a National Heart, Lung, and Blood Institute workshop. Circulation, 119: 606-618
[56] Chou CC, Chen PS, (2009). New concepts in atrial fibrillation: neural mechanisms and calcium dynamics. Cardiol Clin, 27: 35-43
[57] Chen PS, Wu TJ, Ikeda T, Onf JJ, Kim YH, Yashima M, et al. (1998). Focal source hypothesis of atrial fibrillation. J Electrocardiol, 31 Suppl: 32-34
[58] Gilmour Jr RF, Zipes DP, (2004). Mechanisms of disease: new mechanisms of antiarrhythmic actions. Nat Clin Pract Cardiovasc Med, 1: 37-41
[59] Moe GK, Rheinboldt WC, Abildskov JA, (1964). A computer model of atrial fibrillation. Am Heart J, 67: 200-220
[60] Kapa S, Asirvatham SJ, (2009). Atrial fibrillation: focal or reentrant or both? A new autonomic lens to examine an old riddle. Circ Arrhythm Electrophysiol, 2: 345-348
[61] Saltzman HE, (2014). Arrhythmias and heart failure. Cardiol Clin, 32: 125-133
[62] Coote JH, (2013). Myths and realities of the cardiac vagus. J Physiol, 591: 4073-4085
[63] Gaztanaga L, Matchlinski FE, Betensky BP, (2012). Mechanisms of cardiac arrhythmias. Rev Esp Cardiol, 65: 174-185
[64] Finet JE, Rosenbaum DS, Donahue JK, (2009). Information learned from animal models of atrial fibrillation. Cardiol Clin, 27: 45-54
[65] Cabo C, Wit AL, (1997). Cellular electrophysiologic mechanisms of cardiac arrhythmias. Cardiol Clin, 15: 517-538
[66] Nattel S, Burstein B, Dobrev D, (2008). Atrial Remodeling and atrial fibrillation: mechanisms and implications. Circ Arrhythm Electrophysiol, 1: 62-73
[67] Campbell K, Calvo CJ, Mironov S, Herron T, Berenfeld O, (2012). Spatial gradients in action potential duration created by regional magnetofection of hERG are a substrate for wavebreak and turbulent propagation in cardiomyocyte monolayers. J Physiol, 590: 6363-6379
[68] DiFrancesco D, Borer JS, (2007). The funny current: cellular basis for the control of heart rate. Drugs, 67 Suppl 2: 15-24.
[69] Grant AO, (2009). Cardiac ion channels. Circ Arrhythm Electrophysiol, 2: 185-194
[70] Workman AJ, Kane KA, Rankin AC, (2008). Cellular bases for human atrial fibrillation. Heart Rhythm, 5: S1-S6
[71] John RM, Tedrow UB, Koplan BA, Albert CA, Epstein LM, Sweeney MO, et al. (2012). Ventricular arrhythmias and sudden cardiac death. Lancet, 380: 1520-1529
[72] Zipes DP, Knope RF, (1972). Electrical properties of the thoracic veins. Am J Cardiol, 29: 372-376
[73] Masani F, (1986). Node-like cells in the myocardial layer of the pulmonary vein of rats: an ultrastructural study. J Anat, 145: 133-142
[74] Tan AY, Chen PS, Chen LS, Fishbein MC, (2007). Autonomic nerves in pulmonary veins. Heart Rhythm, 4: S57-S60
[75] Shen MJ, Zipes DP, (2014). Role of the autonomic nervous system in modulating cardiac arrhythmias. Circ Res, 114: 1004-1021
[76] Haissaguerre M, Jais P, Shah DC, Takahashi A, Hocini M, Quiniou G, et al. (1998). Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med, 339: 659-666
[77] Jais P, Haissaguerre M, Shah DC, Chouairi S, Gencel L, Jocini M, et al. (1997). A focal source of atrial fibrillation treated by discrete radiofrequency ablation. Circulation, 95: 572-576
[78] Oral H, Ozaydin M, Tada H, Chugh A, Scharf C, Hassan S, et al. (2002). Mechanistic significance of intermittent pulmonary vein tachycardia in patients with atrial fibrillation. J Cardiovasc Electrophysiology, 13: 645-650
[79] Tsai C, Tai C, Hsieh M, Lin WS, Yu WC, Ueng KC, et al. (2000). Initiation of atrial fibrillation by ectopic beats originating from the superior vena cava: electrophysiological characteristics and results of radiofrequency ablation. Circulation, 102: 67-74
[80] Chen YC, Chen SA, Chen YJ, Chang MS, Chan P, Lin CI, (2002). Effects of thyroid hormone on the arrhythmogenic activity of pulmonary vein cardiomyocytes. J Am Coll Cardiol, 39: 366-372
[81] Mathew ST, Patel J, Joseph S, (2009). Atrial fibrillation: mechanistic insights and treatment options. Eur J Intern Med, 20: 672-681
[82] Dorian P, (2005). Antiarrhythmic action of beta-blockers: potential mechanisms. J Cardiovasc Pharmacol Therapeut, 10 Suppl: s15-s22
[83] Yang ZF, Wang HW, Zheng YQ, Zhang Y, Liu YM, Li CZ, (2008). Possible arrhythmiogenic mechanism produced by ibuprofen. Acta Pharmacol Sin, 29: 421-429
[84] Chou CC, Zhou S, Tan AY, Hayashi H, Nihei M, Chen PS, (2005). High-density mapping of pulmonary veins and left atrium during ibutilide administration in a canine model of sustained atrial fibrillation. Am J Physiol Heart Circ Physiol, 289: H2704-H2713
[85] Hamabe A, Okuyama Y, Miyauchi Y, Zhou S, Pak HN, Karagueuzian HS, et al. (2003). Correlation between anatomy and electrical activation in canine pulmonary veins. Circulation, 107: 1550-1555
[86] Klatsky AL, (2009). Alcohol and cardiovascular diseases. Expert Rev Cardiovasc Ther, 7: 499-506
[87] Rosenberg MA, Manning WJ, (2012). Diastolic dysfunction and risk of atrial fibrillation: a mechanistic appraisal. Circulation, 126: 2353-2362
[88] Guasch E, Benito B, Qi X, Cifelli C, Naud P, Shi Y, et al. (2013). Atrial fibrillation promotion by endurance exercise: demonstration and mechanistic exploration in an animal model. J Am Coll Cardiol, 62: 68-77
[89] Saygili E, Rana OR, Reuter H, Frank K, Schwinger RH, Muller-Ehmsen J, et al. Losartan prevents stretch-induced electrical remodeling in cultured atrial neonatal myocytes. Am J Physiol Heart Circ Physiol, 292: H2898-H2905
[90] Arora R, Ng J, Ulphani J, Mylonas I, Subacius H, Shade G, et al. (2007). Unique autonomic profile of the pulmonary veins and posterior left atrium. J Am Coll Cardiol, 49: 1340-1348
[91] Cheung DW, (1981). Electrical activity of the pulmonary vein and its interaction with the right atrium in the guinea pig. J Physiol, 314: 445-456
[92] Bielecka-Dabrowa A, Mikhailidis DP, Rysz J, Banach M, (2009). The mechanisms of atrial fibrillation in hyperthyroidism. Thyroid Research, 2: 4
[93] Hu Y, Jones SV, Dillmann WH, (2005). Effects of hyperthyroidism on delayed rectifier potassium currents in left and right murine atria. Am J Physiol Heart Circ Physiol, 289: H1448-1455
[94] Fox CS, Parise H, D’Agostino RB, Lloyd-Jones DM, Vasan RS, Wang TJ, et al. (2004). Parental atrial fibrillation as a risk factor for atrial fibrillation in offspring. JAMA, 291: 2851-2855
[95] Guo Y, Lip GYH, Apostolakis S, (2012). Inflammation in atrial fibrillation. J Am Coll Cardiol, 60: 2263-2270
[96] Hu YF, Chen YJ, Lin YJ, Chen SA, (2015). Inflammation and the pathogenesis of atrial fibrillation. Nat Rev Cardiol, 12: 230-243
[97] Palin CA, Kailasam R, Hogue CW Jr., (2004). Atrial fibrillation after cardiac surgery: pathophysiology and treatment. Semin in Cardiothorac and Vasc Anesth, 8: 175-183
[98] Bidar E, Bramer S, Maesen B, Maessen JG, Schotten U, (2013). Post-operative atrial fibrillation - pathophysiology, treatment and prevention. J Atr Fibrillation, 5: 136-145
[99] Ishii Y, Schuessler RB, Gaynor SL, Yamada K, Fu AS, Boineau JP, et al. (2005). Inflammation of atrium after cardiac surgery is associated with inhomogeneity of atrial conduction and atrial fibrillation. Circulation, 111: 2881-2888
[100] Terrenoire C, Clancy CE, Cormier JW, Sampson KJ, Kass RS, (2005). Autonomic control of cardiac action potentials: role of potassium channel kinetics in response to sympathetic stimulation. Circ Res, 96: e25-e34
[101] Chen PS, Tan AY, (2007). Autonomic nerve activity and atrial fibrillation. Heart Rhythm, 4 Suppl 3: S61-S64
[102] Grassi G, Seravalle G, Dell’Oro R, Turri C, Pasqualinotto L, Colombo M, et al. (2001). Participation of the hypothalamic-pituitary axis in the sympathetic activation of human obesity. Hypertension, 38: 1316-1320
[103] Aytemir K, Deniz A, Yavuz B, Ugur Demir A, Sahiner L, Cifti O, et al. (2006). Increased myocardial vulnerability and autonomic nervous system imbalance in obstructive sleep apnea syndrome. Respir Med, 101: 1277-1282
[104] Roche F, Xuong ANT, Court-Fortune I, Costes F, Pichot V, Duverney D, et al. (2003). Relationship among the severity of sleep apnea syndrome, cardiac arrhythmias, and autonomic imbalance. Pacing Clin Electrophysiol. 26: 669-677
[105] Grippo AJ, Moffitt JA, Johnson AK, (2002). Cardiovascular alterations and autonomic imbalance in an experimental model of depression. Am J Physiol Regulatory Integrative Comp Physiol, 282: R1333-R1341
[106] Carnethon MR, Jacobs DR, Sidney S, Liu K, (2003). Influence of autonomic nervous system dysfunction on the development of Type 2 Diabetes: The CARDIA Study. Diabetes Care, 26: 3035-3041
[107] Wright RJ, (2012). Stress-related programming of autonomic imbalance: role in allergy and asthma. Chem Immunol Allergy, 98: 32-47
[108] Thayer JF, Yamamoto SS, Brosschot JF, (2010). The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors. Int J Cardiol, 141: 122-131
[109] Florea VG, Cohn JN, (2014). The autonomic nervous system and heart failure. Circ Res, 114: 1815-1826
[110] Binkley PF, Nunziata E, Haas GJ, Nelson SD, Cody RJ, (1991). Parasympathetic withdrawal is an integral component of autonomic imbalance in congestive heart failure: demonstration in human subjects and verification in a paced canine model of ventricular failure. J Am Coll Cardiol, 18: 464-472
[111] Iellamo F, Legramante JM, Pigozzi F, Spataro A, Norbiato G, Lucini D, et al. (2002). Conversion from vagal to sympathetic predominance with strenuous training in high-performance world class athletes. Circulation, 105: 2719-2724
[112] Yamamoto K, Miyachi M, Saitoh T, Yoshioka A, Onodera S, (2001). Effects of endurance training on resting and post-exercise cardiac autonomic control. Med Sci Sports Exerc, 33: 1496-1502
[113] Pichot V, Busso T, Roche F, Garet M, Costes F, Duverney D, et al. (2002). Autonomic adaptations to intensive and overload training periods: a laboratory study. Med Sci Sports Exerc, 34: 1660-1666
[114] Sharifov OF, Fedorov VV, Beloshapko GG, Glukhov AV, Yushmanova AV, Rosenshtraukh LV, (2004). Roles of adrenergic and cholinergic stimulation in spontaneous atrial fibrillation in dogs. J Am Coll Cardiol, 43: 483-490
[115] Zhou Q, Hu J, Guo Y, Zhang F, Yang X, Zhang L, et al. (2013). Effect of the stellate ganglion on atrial fibrillation and atrial electrophysiological properties and its left-right asymmetry in a canine model. Exp Clin Cardiol, 18: 38-42
[116] Coumel P, (1994). Paroxysmal atrial fibrillation: a disorder of autonomic tone? Eur Heart J, 15 Suppl: 9-16
[117] Tomita T, Takei M, Saikawa Y, Hanaoka T, Uchikawa SI, Tsutsui H, et al. Role of autonomic tone in initiation and termination of paroxysmal atrial fibrillation in patients without structural heart disease. J Cardiovasc Electrophysiol, 14: 559-564
[118] Bettoni M, Zimmerman M, (2002). Autonomic tone variations before the onset of paroxysmal atrial fibrillation. Circulation, 105: 2753-2759
[119] Gould PA, Yii M, McLean C, Finch S, Marshall T, Lambert GW, et al. (2006). Evidence for increased atrial sympathetic innervation in persistent human atrial fibrillation. Pacing Clin Electrophysiol, 29: 821-829
[120] Deneke T, Chaar H, de Groot JR, Wilde AA, Lawo T, Mundig J, et al. (2011). Shift in the pattern of autonomic atrial innervation in subjects with persistent atrial fibrillation. Heart Rhythm, 8: 1357-1363
[121] Patterson E, Po SS, Scherlag BJ, Lazzara R, (2005). Triggered firing in pulmonary veins initiated by in vitro autonomic stimulation. Heart Rhythm, 2: 624-631
[122] Amar D, Zhang H, Miodownik S, Kadish AH, (2003). Competing autonomic mechanisms precede the onset of postoperative atrial fibrillation. J Am Coll Cardiol, 42: 1262-1268
[123] Thayer JF, Lane RD, (2007). The role of vagal function in the risk for cardiovascular disease and mortality. Biol Psychol, 74: 224-242
[124] Brooks AG, Stiles MK, Laborderie J, Lau DH, Kuklik P, Shipp NJ, et al. (2010). Outcomes of long-standing persistent atrial fibrillation ablation: a systematic review. Heart Rhythm, 7: 835-846
[125] Thayer JF, (2009). Vagal tone and the inflammatory reflex. Cleve Clinic J Med, 76 Suppl 2: S23-S26
[126] Feldstein C, Julius S, (2009). The complex interaction between overweight, hypertension, and sympathetic overactivity. J Am Soc of Hypertens, 3: 353-365
[127] O’Connor TM, O’Halloran DJ, Shanahan F, (2000). The stress response and the hypothalamic-pituitary-adrenal axis: from molecule to melancholia. Q J Med, 93: 323-333
[128] Benarroch EE, (1993). The central autonomic network: functional organization, dysfunction, and perspective. Mayo Clin Proc, 68: 988-1001
[129] McEwen BS, (2000). The neurobiology of stress: from serendipity to clinical relevance. Brain Res, 886: 172-189
[130] Ulrich-Lai YM, Herman JP, (2009). Neural regulation of endocrine and autonomic stress responses. Nat Rev Neurosci, 10: 397-409
[131] Schlenker EH, (2005). Integration in the PVN: another piece of the puzzle. Am J Physiol Regul Integr Comp Physiol, 289: R653-655
[132] Dampney RA, Coleman MJ, Fontes MA, Hirooka Y, Horiuchi J, Li YW, et al. (2002). Central mechanisms underlying short-term and long-term regulation of the cardiovascular system. Clin Exp Pharmacol Physiol, 29: 261-268
[133] Machado BH, Mauad H, Chianca Junior DA, Haibara AS, Colombari E, (1997). Autonomic processing of the cardiovascular reflexes in the nucleus tractus solitarii. Braz J Med Biol Res, 30: 533-543
[134] LaBar KS, Cabeza R, (2006). Cognitive neuroscience of emotional memory. Nat Rev Neurosci, 7: 54-64
[135] LeDoux J, (2003). The emotional brain, fear, and the amygdala. Cell and Mol Neurobiol, 23: 727-738
[136] Phelps EA, (2004). Human emotion and memory: interactions of the amygdala and hippocampal complex. Curr Opin Neurobiol, 14: 198-202
[137] Veinante P, Yalcin I, Barrot M, (2013). The amygdala between sensation and affect: a role in pain. J Mol Psychiatry, 1: 9-23
[138] Everly GS, Lating JM, (2013). The Anatomy and Physiology of the Human Stress Response. In: Everly GS, Lating JM. A Clinical Guide to the Treatment of the Human Stress Response, 3rd ed. New York: Springer Science + Business Media, 17-51
[139] Sah P, Faber ES, Lopez de Armentia M, Power J., (2003). The amygdaloid complex: anatomy and physiology. Physiol Rev, 83: 803-834
[140] Vyas A, Bernal S, Chattarji S, (2003). Effects of chronic stress on dendritic arborization in the central and extended amygdala. Brain Res, 965: 290-294
[141] Vyas A, Pillai AG, Chattarji S, (2004). Recovery after chronic stress fails to reverse amygdaloid neuronal hypertrophy and enhanced anxiety-like behavior. Neuroscience 128: 667-673
[142] Vyas A, Jadhav S, Chattarji S, (2006). Prolonged behavioral stress enhances synaptic connectivity in the basolateral amygdala. Neuroscience, 143: 387-393
[143] Alkadhi K, (2013). Brain physiology and pathophysiology in mental stress. ISRN Physiology, 2013: 806104
[144] Palkovits M, (1999). Interconnections between the neuroendocrine hypothalamus and the central autonomic system. Front Neuroendocrinol, 20: 270-295
[145] Carlson LE, Campbell TS, Garland SN, Grossman P, (2007). Associations among salivary cortisol, melatonin, catecholamines, sleep quality and stress in women with breast cancer and healthy controls. J Behav Med, 30: 45-58
[146] Kirschbaum C, Hellhammer DH, (1994). Salivary cortisol in psychoneuroendocrine research: recent developments and applications. Psychoneuroendocrinology, 19: 313-333
[147] Wood SK, (2014). Cardiac autonomic imbalance by social stress in rodents: understanding putative biomarkers. Front Psychol, 5: 950
[148] Cacioppo JT, Burleson MH, Poehlmann KM, Malarkey WB, Kiecolt-Glaser JK, Berntson GG, et al. (2000). Autonomic and neuroendocrine responses to mild psychological stressors: effects of chronic stress on older women. Ann Behav Med, 22: 140-148
[149] Vrijkotte TG, van Doornen LJ, de Geus EJ, (2000). Effects of work stress on ambulatory blood pressure, heart rate, and heart rate variability. Hypertension, 35: 880-886
[150] Takase B, Akima T, Satomura K, Ohsuzu F, Mastui T, Ishihara M, et al. (2004). Effects of chronic sleep deprivation on autonomic activity by examining heart rate variability, plasma catecholamine, and intracellular magnesium levels. Biomed Pharmacother, 58 Suppl: S35-S39
[151] Lange HW, Herrmann-Lingen C, (2007). Depressive symptoms predict recurrence of atrial fibrillation after cardioversion. J Psychosom Res, 63: 509-513
[152] Yu SB, Hu W, Zhao QY, Qin M, Huang H, Cui HY, et al. (2012). Effect of anxiety and depression on the recurrence of persistent atrial fibrillation after circumferential pulmonary vein ablation. Chin Med J (Engl), 125: 4368-4372
[153] Wyndham CR, (2000). Atrial fibrillation: the most common arrhythmia. Texas Heart Institute Journal, 27: 257-267
[154] Wijffels MC, Kirchhof CJ, Dorland R, Allessies MA, (1995). Atrial fibrillation begets atrial fibrillation: a study in awake chronically instrumented goats. Circulation, 92: 1954-1968
[155] Jalife J, (2014). Novel upstream approaches to prevent atrial fibrillation perpetuation. Cardiol Clin, 32: 637-650
[156] Ausma J, Litjens N, Lenders MH, Duimel H, Mast F, Wouters L, et al. (2001). Time course of atrial fibrillation-induced cellular structural remodeling in atria of the goat. J Mol Cell Cardiol, 33: 2083-2094
[157] Ausma J, van der Velden HM, Lenders MH, van Ankeren EP, Jongsma HJ, Ramaekers FC, et al. (2003). Reverse structural and gap-junctional remodeling after prolonged atrial fibrillation in the goat. Circulation, 107: 2051-2058
[158] Camelliti P, Borg TK, Kohl P, (2005). Structural and functional characterization of cardiac fibroblasts. Cardiovasc Res, 65: 40-51
[159] Souders CA, Bowers SL, Baudino TA, (2009). Cardiac fibroblast: the renaissance cell. Circ Res, 105: 1164-1176
[160] Partemi S, Batlle M, Berne P, Berruezo A, Campos B, Mont L, et al. (2013). Analysis of the arrhythmogenic substrate in human heart failure. Cardiovasc Pathol, 22: 133-140
[161] Cuspidi C, Ciulla M, Zanchetti A, (2006). Hypertensive myocardial fibrosis. Nephrol Dial Transplant, 21: 20-23
[162] Aronow WS, (2008). Etiology, pathophysiology, and treatment of atrial fibrillation: part 1. Cardiol Rev, 16: 181-188
[163] Wolf PA, Abbott RD, Kannel WB, (1991). Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke, 22: 983-988
[164] Dimitri H, Ng M, Brooks AG, Kuklik P, Stiles MK, Lau DH, et al. (2012). Atrial remodeling in obstructive sleep apnea: implications for atrial fibrillation. Heart Rhythm, 9: 321-327
[165] Marott SC, Nordestgaard BG, Zacho J, Friberg J, Jensen GB, Tybjaerg-Hansen A, et al. (2010). Does elevated C-reactive protein increase atrial fibrillation risk? A Mendelian randomization of 47,000 individuals from the general population. J Am Coll Cardiol, 56: 789-795
[166] Marcus GM, Smith LM, Ordovas K, Scheinman MM, Kim AM, Badhwar N, et al. (2010). Intracardiac and extracardiac markers of inflammation during atrial fibrillation. Heart Rhythm, 7: 149-154
[167] Rizos R, Rigopoulos AG, Kalogeropoulos AS, Tsiodras S, Dragomanovits S, Sakadakis EA, et al. (2010). Hypertension and paroxysmal atrial fibrillation: a novel predictive role of high sensitivity C-reactive protein in cardioversion and long-term recurrence. J Hum Hypertens, 24: 447-457
[168] Li J, Solus J, Chen Q, Rho YH, Milne G, Stein CM, et al. (2010). Role of inflammation and oxidative stress in atrial fibrillation. Heart Rhythm, 7: 438-444
[169] Chung MK, Martin DO, Sprecher D, Wazni O, Kanderian A, Carnes CA, et al. (2001). C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation, 104: 2886-2891
[170] Patti G, Chello M, Candura D, Pasceri V, D’Ambrosio A, Covino E, et al. (2006). Randomized trial of atorvastatin for reduction of postoperative atrial fibrillation in patients undergoing cardiac surgery: results of the ARMYDA-3 (Atorvastatin for Reduction of MYocardial Dysrhythmia After cardiac surgery) study. Circulation, 114: 1455-1461
[171] Ho KM, Tan JA, (2009). Benefits and risks of corticosteroid prophylaxis in adult cardiac surgery: a dose-response meta-analysis. Circulation. 119: 1853-1866
[172] Hatem S, Le Grand B, Le Heuzey JY, Couetil JP, Droubaix E, (1992). Differential effects of quinidine and flecainide on plateau duration of human atrial action potential duration. Basic Res Cardiol. 87: 600-609
[173] Hiraoka M, Sawada K, Kawano S, (1986). Effects of quinidine on plateau currents of guinea-pig ventricular myocytes. J Mol Cell Cardiol, 19: 1097-1106
[174] Bhakta D, Miller JM, (2007). Pharmacologic targets for atrial fibrillation. Expert Opin Ther Targets, 11: 1161-1178
[175] Ridley JM, Milnes JT, Benest AV, Masters JD, Witchel HJ, Hancox JC, (2003). Characterization of recombinant HERG K+ channel blockade by the class Ia antiarrhythmic drug procainamide. Biochem and Biophys Res Commun, 306: 388-393
[176] Tsujimae K, Suzuki S, Yamada M, Kurachi Y, (2004). Comparison of kinetic properties of quinidine and dofetilide block of HERG channels. Eur J Pharmacol, 493: 29-40
[177] Paul AA, Witchel HJ, Hancox JC, (2002). Inhibition of the current of heterologously expressed HERG potassium channels by flecainide and comparison with quinidine, propafenone and lignocaine. Br J Pharmacol 135: 717-729
[178] Falk RH, (1989). Flecainide-induced ventricular tachycardia and fibrillation in patients treated for atrial fibrillation. Ann Intent Med, 111: 107-111
[179] Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, et al. (1991). Mortality and Morbidity in patients receiving encainide, flecainide, or Vaughan—The Cardiac Arrhythmia Suppression Trial. N Engl J Med, 324: 782-788
[180] Greene HL, Roden DM, Katz RJ, Woosley RL, Salerno DM, Henthorn RW, (1992). The cardiac arrhythmia suppression trial: First CAST then CAST II. J Am Coll Cardiol, 19: 894-898
[181] Purerfellner H, (2004). Recent developments in cardiovascular drug therapy: treatment of atrial arrhythmias with new class III drugs and beyond. Curr Med Chem Cardiovasc Hematol Agents, 2: 79-91
[182] Coplen SE, Antmann EM, Berlin JA, Hewitt P, Chalmers TC, (1990). Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion: a meta-analysis of randomized controlled trials. Circulation, 82: 1106-1116
[183] Reiffel JA, Naccarelli GV, (2006). Antiarrhythmic drug therapy for atrial fibrillation: Are the guidelines guiding clinical practice? Clin Cardiol, 29: 97-102
[184] Connolly SJ, Cybulsky I, Lamy A, Roberts RS, O’Brien B, Carroll S, et al. (2003). Double-blind, placebo-controlled, randomized trial of prophylactic metoprolol for reduction of hospital length of stay after heart surgery: the beta-Blocker Length Of Stay (BLOS) study. Am Heart J, 145: 226-232
[185] Coleman CI, Perkerson KA, Gillespie EL, Kluger J, Gallagher R, Horowitz S, et al. (2004). Impact of prophylactic post-operative beta-blockade on post-cardiothoracic surgery length of stay and atrial fibrillation. Ann Pharmacother, 38: 2012-2016
[186] Ferguson TB Jr, Coombs LP, Peterson ED, (2002). Preoperative beta-blocker use and mortality and morbidity following CABG surgery in North America. JAMA, 287: 2221-2227
[187] Shenasa M, Kus T, Fromer M, LeBlanc RA, Dubuc M, Nadeau R, (1988). Effect of intravenous and oral calcium antagonists (diltiazem and verapamil) on sustenance of atrial fibrillation. Am J Cardiol, 62: 403-407
[188] Lally JA, Gnall EM, Seltzer J, Kowey PR, (2007). Non-antiarrhythmic drugs in atrial fibrillation: a review of non-antiarrhythmic agents in prevention of atrial fibrillation. J Cardiovasc Electrophysiol, 18: 1222-1228
[189] Sticherling C, Behrens S, Kamke W, Stahn A, Zabel M, (2005). Comparison of acute and long-term effects of single-dose amiodarone and verapamil for the treatment of immediate recurrences of atrial fibrillation after transthoracic cardioversion. Europace, 7: 546-553
[190] Waldo AL, Camm AJ, DeRuyter H, Friedman PL, MacNeil DJ, Pauls JF, et al. (1996). Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival with Oral d-Sotalol. Lancet, 348: 7-12
[191] Patel A, Dunning J, (2005). Is sotalol more effective than standard beta-blockers for prophylaxis of atrial fibrillation during cardiac surgery? Interactive Cardiovascular and Thoracic Surgery, 4: 147-150
[192] McClellan KJ, Markham A, (1999). Dofetilide: a review of its use in atrial fibrillation and atrial flutter. Drugs, 58: 1043-1059
[193] Singh S, Zoble RG, Yellen L, Brodsky MA, Feld GK, Berk M, et al. (2000). Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter: the symptomatic atrial fibrillation investigative research on dofetilide (SAFIRE-D) study. Circulation, 102: 2385-90
[194] Falk RH, DeCara JM, (2000). Dofetilide: A new pure class III antiarrhythmic agent. Am Heart J, 140: 697-706
[195] Banchs JE, Wolbrette DL, Samii SM, Penny-Peterson ED, Patel PP, Young SK, et al. (2008). Efficacy and safety of dofetilide in patients with atrial fibrillation and atrial flutter. J Interv Card Electrophysiol, 23: 111-115
[196] Torp-Pedersen C, Moller M, Bloch-Thomsen PE, Kober L, Sandoe E, Egstrup K, et al. (1999). Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. N Engl J Med, 341: 857-865
[197] Lauer MR, (2001). Dofetilide: Is the treatment worse than the disease? J Am Coll Cardiol, 37: 1106-1110
[198] Van Erven L, Schalij MJ, (2010). Amiodarone: an effective antiarrhythmic drug with unusual side effects. Heart, 96: 1593-1600
[199] Bagshaw SM, Galbraith D, Mitchell B, Sauve R, Exner DV, Ghali WA, (2006). Prophylactic amiodarone for prevention of atrial fibrillation after cardiac surgery: a meta-analysis. Ann Thorac Surg, 82: 1927-1937
[200] Danzi S, Klein I, (2015). Amiodarone-induced thyroid dysfunction. J Intensive Care Med, 30: 179-195
[201] Blackshear JL, Stafford RE, (2003). AFFIRM and RACE trials: implications for the management of atrial fibrillation. Card Electrophysiol Rev, 7: 366-369
[202] Carlsson J, Miketic S, Windeler J, Cuneo A, Haun S, Micus S, et al. (2003). Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation: the Strategies of Treatment of Atrial Fibrillation (STAF) study. J Am Coll Cardiol, 41: 1690-1696
[203] Heist EK, Mansour M, Raskin JN, (2011). Rate control in atrial fibrillation: targets, methods, resynchronization considerations. Circulation, 124: 2746-2755
[204] Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, et al. (2002). A comparison of rate control and rhythm control in patients with atrial fibrillation. N Eng J Med, 347: 1825-1833
[205] Ad N, (2007). The Cox-Maze procedure: history, results, and predictors for failure. J Interv Card Electrophysiol, 20: 65-71
[206] Harling L, Athanasiou T, Ashrafian H, Nowell J, Kourliouros A, (2011). Strategies in the surgical management of atrial fibrillation. Cardiol Res Pract, 2011: 439312
[207] Cox JL, Schuessler RB, Lappas DG, Boineau JP, (1996). An 8 ½-year clinical experience with surgery for atrial fibrillation. Ann Surg, 224: 267-273
[208] McCarthy PM, Gillinov AM, Castle L, Chung M, Cosgrove D, (2000). The Cox-Maze procedure: the Cleveland Clinic experience. Semin Thorac Cardiovasc Surg, 12: 25-29
[209] Schaff HV, Dearani JA, Daly RC, Orszulak TA, Danielson GK, (2000). Cox-Maze procedure for atrial fibrillation: Mayo Clinic experience. Semin Thorac Cardiovasc Surg, 12: 30-37
[210] Cox JL, Boineau JP, Schuessler RB, Jaquiss RD, Lappas DG, (1995). Modifications of the maze procedure for atrial flutter and atrial fibrillation. I. Rationale and surgical results. J Thorac Cardiovas Surg, 110: 473-484
[211] Cox JL, Jaquiss RD, Schuessler RB, Boineau JP, (1995). Modifications of the maze procedure for atrial flutter and atrial fibrillation. II. Surgical technique of the maze III procedure. J Thorac Cardiovas Surg, 110: 485-495
[212] Ballaux PK, Geuzebroek GS, van Hemmel NM, Kelder JC, Dossche KM, Ernst JM, et al. (2006). Freedom from atrial arrhythmias after classic maze III surgery: a 10-year experience. J Thorac Cardiovasc Surg, 132: 1433-1440
[213] Prasad SM, Maniar HS, Camillo CJ, Schuessler RB, Boineau JP, Sundt TM, et al. (2003). The Cox maze III procedure for atrial fibrillation: long-term efficacy in patients undergoing lone versus concomitant procedures. J Thorac Cardiovasc Surg, 126: 1822-1828
[214] Damiano RJ, Gaynor SL, Bailey M, Prasad S, Cox JL, Boineau JP, et al. (2003). The long-term outcome of patients with coronary disease and atrial fibrillation undergoing the Cox maze procedure. J Thorac Cardiovasc Surg, 126: 2016-2021
[215] Altman RK, Proietti R, Barrrett CD, Paoletti Perini A, Santangeli P, Danik SB, et al. (2014). Management of refractory atrial fibrillation post-surgical ablation. Ann Cardiothorac Surg, 3: 91-97
[216] Schmidt C, Kisselback J, Schweizer PA, Katus HA, Thomas D, (2011). The pathology and treatment of cardiac arrhythmias: focus on atrial fibrillation. Vasc Health Risk Manag, 7: 193-202
[217] Maroto LC, Carnero M, Silva JA, Cobiella J, Perez-Castellano N, Reguillo F, et al. (2011). Early recurrence is a predictor of late failure in surgical ablation of atrial fibrillation. Interact Cardiovasc Thorac Surg, 12: 681-686
[218] Gaynor SL, Schuessler RB, Bailey MS, Ishii Y, Boineau JP, Gleva MJ, et al. (2005). Surgical treatment of atrial fibrillation: predictors of late recurrence. J Thorac Cardiovasc Surg, 129: 104-111
[219] Kawaguchi AT, Kosakai YK, Isobe F, Sasako Y, Eishi K, Nakano K, et al. (1996). Factors affecting rhythm after the maze procedure for atrial fibrillation. Circulation, 94 Suppl: II139-142
[220] Ishii Y, Gleva MJ, Gamache C, Schuessler RB, Boineau JP, Bailey MS, et al. (2004). Atrial tachyarrhythmias after the maze procedure: incidence and prognosis. Circulation, 110 Suppl: II164-168
[221] Golovchiner G, Mazur A, Kogan A, Strasberg B, Shapira Y, Fridman M, et al. (2005). Atrial flutter after surgical radiofrequency ablation of the left atrium for atrial fibrillation. Ann Thorac Surg, 79: 108-112
[222] Kik C, Bogers AJ, (2011). Maze procedures for atrial fibrillation, from history to practice. Cardiol Res, 2: 201-207
[223] Lonnerholm S, Blomstrom P, Nilsson L, Blostrom-Lundqvist C, (2008). Long-term effects of the maze procedure on atrial size and mechanical function. Ann Thor Surg, 85: 916-920
[224] Stulak JM, Sundt TM III, Dearani JA, Daly RC, Orsulak TA, Schaff HV, (2007) . Ten-year experience with the Cox-maze procedure for atrial fibrillation: how do we define success? Ann Thor Surg, 83: 1319
[225] McCarthy PM, Castle LW, Maloney JD, Trohman RG, Simmons TW, White RD, et al. (1993). Initial experience with the maze procedure for atrial fibrillation. J Thorac Cardiovasc Surg, 105: 1077-1087
[226] Calkins H, Reynolds MR, Spector P, Sondhi M, Xu Y, Martin A, et al. (2009). Treatment of atrial fibrillation with antiarrhythmic drugs or radiofrequency ablation: two systematic literature reviews and meta-analyses. Circ Arrhythm Electrophysiol, 2: 349-361
[227] Wynn GJ, Das M, Bonnett LJ, Panikker S, Wong T, Gupta D, (2014). Efficacy of catheter ablation for persistent atrial fibrillation: a systematic review and meta-analysis of evidence from randomized and nonrandomized controlled trials. Circ Arrhythm Electrophysiol, 7: 841-852
[228] Joseph JP, Rajappan K, (2012). Radiofrequency ablation of cardiac arrhythmias: past, present and future. QJM, 105: 303-314
[229] Hanley C, Esberg D, Kowey PR, (2014). Ablation versus drugs: what is the best first-line therapy for paroxysmal atrial fibrillation? Antiarrhythmic drugs are outmoded and catheter ablation should be the first-line options for all patients with paroxysmal atrial fibrillation: con. Circ Arrh Electrophysiol, 7: 747-754
[230] Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman J, et al. (2005). Worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circulation, 111: 1100-1105
[231] Shah RU, Freeman JV, Shilane D, Wang PJ, Go AS, Hlatky MA, (2012). Procedural complications, rehospitalizations, and repeat procedures after catheter ablation for atrial fibrillation. J Am Coll Cardiol, 59: 143-149
[232] Sciarra L, Rebecchi M, De Ruvo E, De Luca L, Zuccaro LM, Fagagnini A, et al. (2010). How many atrial fibrillation candidates have an underlying supraventricular tachycardia previously unknown? Efficacy of isolated triggering arrhythmia ablation. Europace, 12: 1707-1712
[233] Castrejon-Castrejon S, Ortega M, Perez-Silva A, Doiny D, Estrada A, Filgueiras D, et al. (2011). Organized atrial tachycardias after atrial fibrillation ablation. Cardiol Res Pract, 2011: 957538
[234] Chugh A, Oral H, Lemola K, Hall B, Cheung P, Good E, et al. (2005). Prevalence, mechanism, and clinical significance of macroreentrant atrial tachycardia during and following left atrial ablation for atrial fibrillation. Heart Rhythm, 2: 464-471
[235] Deisenhofer I, Estner H, Zrenner B, Schreieck J, Weyerbrock S, Hessling G, et al. (2006). Left atrial tachycardia after circumferential pulmonary vein ablation for atrial fibrillation: incidence, electrophysiological characteristics, and results of radiofrequency ablation. Europace, 8: 573-582
[236] Lee G, Sanders P, Kalman JM, (2012). Catheter ablation of atrial arrhythmias: state of the art. Lancet, 380: 1509-1519
[237] Brooks AG, Stiles MK, Laborderie J, Lau DH, Kuklik P, Shipp NJ, et al. (2010). Outcomes of long-standing persistent atrial fibrillation ablation: a systematic review. Heart Rhythm, 7: 835-846
[238] Hoyer FF, Lickfett LM, Mittmann-Braun E, Ruland C, Kreuz J, Pabst S, et al. (2010). High prevalence of obstructive sleep apnea in patients with resistant paroxysmal atrial fibrillation after pulmonary vein isolation. J Interv Card Electrophysiol, 29: 37-41
[239] Monahan D, Redline S., (2011). Role of obstructive sleep apnea in cardiovascular disease. Curr Opin Cardiol, 26: 541-547
[240] Santangeli P, Di Biase L, Natale A, (2014). Ablation versus drugs: what is the best first-line therapy for paroxysmal atrial fibrillation? Antiarrhythmic drugs are outmoded and catheter ablation should be the first-line options for all patients with paroxysmal atrial fibrillation: Pro. Circ Arrhythm Electrophysiol, 7: 739-746
[241] Olsson A, Darpo B, Bergfeldt L, Rosenqvist M, (1999). Frequency and long term follow up of valvar insufficiency caused by retrograde aortic radiofrequency catheter ablation procedures. Heart, 81: 292-296
[242] Ren JF, Marchlinski FE, Callans DJ, (2004). Left atrial thrombus associated with ablation for atrial fibrillation: identification with intracardaic echocardiography. J Am Coll Cardiol, 43: 1861-1867
[243] Chen SA, Chiang CE, Tai CT, Cheng CC, Chiou CW, Lee SH, et al. (1996). Complications of diagnostic electrophysiologic studies and radiofrequency catheter ablation in patients with tachyarrhythmias: an eight-year survey of 3,966 consecutive procedures in tertiary referral center. Am J Cardiol, 77: 41-46
[244] Robbins IM, Colvin EV, Doyle TP, Kemp WE, Loyd JD, McMahon WS, et al. (1998). Pulmonary vein stenosis after catheter ablation of atrial fibrillation. Circulation, 98: 1769-1775
[245] Li S, Scherlag BJ, Yu L, Sheng X, Zhang Y, Ali R, et al. (2009). Low-level vagosympathetic stimulation: a paradox and potential new modality for the treatment of focal atrial fibrillation. Circ Arrhythm Electrophysiol, 2: 645-651
[246] Katritsis DG, Giazitzoglou E, Zografos T, Pokushalov E, Po SS, Camm AJ, (2011). Rapid pulmonary vein isolation combined with autonomic ganglia modification: a randomized study. Heart Rhythm, 8: 672-678
[247] Lemery R, Birnie D, Tang AS, Green M, Gollob M, (2006). Feasibility study of endocardial mapping of ganglionated plexuses during catheter ablation of atrial fibrillation. Heart Rhythm, 3: 387-396
[248] Scherlag BJ, Nakagawa H, Jackman WM, Yamanashi WS, Patterson E, Po S, et al. (2005). Electrical stimulation to identify neural elements on the heart: their role in atrial fibrillation. J Interv Card Electrophysiol, 13 Suppl: 37-42
[249] Malpas SC, (2010). Sympathetic nervous system overactivity and its role in the development of cardiovascular disease. Physiol Rev, 90: 513-557
[250] Hou Y, Hu J, Po SS, Wang H, Zhang L, Zhang F, et al. (2013). Catheter-based renal sympathetic denervation significantly inhibits atrial fibrillation induced by electrical stimulation of the left stellate ganglion and rapid atrial pacing. Plos One, 8: e78218
[251] Linz D, Mahfoud F, Schotten U, Ukena C, Neuberger HR, Wirth K, et al. (2012). Renal sympathetic denervation suppresses postapneic blood pressure rises and atrial fibrillation in a model for sleep apnea. Hypertension, 60: 172-178
[252] Pokushalov E, Romanov A, Corbucci G, Artyomenko S, Baranova V, Turov A, et al. (2012). A randomized comparison of pulmonary vein isolation with versus without concomitant renal artery denervation in patients with refractory symptomatic atrial fibrillation and resistant hypertension. J Am Coll Cardiol, 60: 1163-1170
[253] Kosiuk J, Pokushalov E, Hilbert S, Hindricks G, Bollmann A, Steinberg JS, (2014). The role of renal sympathetic denervation in atrial fibrillation. J Atr Fibrillation, 6: 91-94
[254] Pathak RK, Middeldorp ME, Meredith M, Mehta AB, Mahajan R, Wong CX, et al. (2015). Long-term effect of goal-directed weight management in an atrial fibrillation cohort: a long-term follow-up study (LEGACY). J Am Coll Cardiol, 65: 2159-2169
[255] Govindarajan G, Alpert MA, Tejwani L, (2008). Endocrine and metabolic effects of fat: cardiovascular implications. Am J Med, 121: 366-370
[256] Fantuzzi G, (2005). Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol, 115: 911-919
[257] Rocha VZ, Libby P, (2009). Obesity, inflammation, and atherosclerosis. Nat Rev Cardiol, 6: 399-409
[258] Romeo GR, Lee J, Shoelson SE, (2012). Metabolic syndrome, insulin resistance, and roles of inflammation - mechanisms and therapeutic targets. Arterioscler Thromb Vasc Biol, 32: 1771-1776
[259] Grassi G, Seravalle G, Cattaneo BM, Bolla FB, Lanfranchi A, Colombo M, et al. (1995). Sympathetic activation in obese normotensive subjects. Hypertension, 25: 560-563
[260] Grassi G, Quarti-Trevano Seravalle G, Dell’Oro R, (2007). Cardiovascular risk and adrenergic overdrive in the metabolic syndrome. Nutr Metab Cardiovasc Dis, 17: 473-481
[261] Grassi G, Seravalle G, Colombo M, Bolla G, Cattaneo BM, Cavagnini F, et al. (1998). Body weight reduction, sympathetic nerve traffic, and arterial baroreflex in obese normotensive humans. Circulation, 97: 2037-2042
[262] DiBona GF, (2004). The sympathetic nervous system and hypertension: recent developments. Hypertension, 43: 147-150
[263] Tvarijonaviciute A, Tecles F, Martinez-Subiela S, Ceron JJ, (2012). Effect of weight loss on inflammatory biomarkers in obese dogs. The Veterinary Journal, 193: 570-572
[264] Cho ZH, Hwang SC, Wong EK, Son YD, Kang CK, Park TS, et al. (2006). Neural substrates, experimental evidences and functional hypothesis of acupuncture mechanisms. Acta Neurol Scand, 113: 370-377
[265] Wang JD, Kuo TB, Yang CC, (2002). An alternative method to enhance vagal activities and suppress sympathetic activities in humans. Auton Neurosci, 100: 90-95
[266] Lombardi F, Belletti S, Battezzati PM, Lomuscio A, (2012). Acupuncture for paroxysmal and persistent atrial fibrillation: an effective non-pharmacological tool? World J Cardiol, 4: 60-65
[267] Lomuscio A, Belletti S, Battezzati P, Lombardi F, (2011). Efficacy of acupuncture in preventing atrial fibrillation recurrences after electrical cardioversion. J Cardiovasc Electrophysiol, 22: 241-247
[268] Jonkman FA, Jonkman-Buidin ML, (2013). Integrated approach to treatment-resistant atrial fibrillation: additional value of acupuncture. Acupunct Med, 31: 327-330
[269] Lakkireddy D, Atkins D, Pillarisetti J, Ryschon K, Bommana S, Drisko J, et al. (2013). Effect of yoga on arrhythmia burden, anxiety, depression, and quality of life in paroxysmal atrial fibrillation: the YOGA My Heart Study. J Am Coll Cardiol, 61: 1177-1182
[270] Kim Y-D, Heo I, Shin B-C, Crawford C, Kang HW, Lim JH, (2013). Acupuncture for Posttraumatic Stress Disorder: A systematic review of randomized controlled trials and prospective clinical trials. Evid Based Complement Alternat Med, 2013: 615857
[271] Streeter CC, Gerbarg PL, Saper RB, Ciraulo DA, Brown RP, (2012). Effects of yoga on the autonomic nervous system, gamma-aminobutyric-acid, and allostasis in epilepsy, depression, and post-traumatic stress disorder. Med Hypotheses, 78: 571-579
[272] van der Kolk BA, Stone L, West J, Rhodes A, Emerson D, Suvak M, et al. (2014). Yoga as an adjunctive treatment for posttraumatic stress disorder: a randomized controlled trial. J Clin Psychiatry, 75: e559-565
[273] Kiecolt-Glaser JK, Bennett JM, Andridge R, Peng J, Shapiro CL, Malarkey WB, et al. (2014). Yoga’s impact on inflammation, mood, and fatigue in breast cancer survivors: a randomized controlled trial. J Clin Oncol, 32: 1040-1049
[274] Vijayaraghava A, Doreswamy V, Narasipur OS, Kunnavil R, Srinivasamurthy N, (2015). Effect of yoga practice on levels of inflammatory markers after moderate and strenuous exercise. J Clin Diagn Res, 9: CC08-CC12
[275] Kavoussi B, Ross BE, (2007). The neuroimmune basis of anti-inflammatory acupuncture. Integr Cancer Ther, 6: 251-257
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