Abstract
Few trials in Cardiology have been so ascertaining of our limited knowledge of cardiac physiology as the Cardiac Arrhythmia Suppression Trial, CAST. That trial made us aware of the complexity of the interaction between antiarrhythmic drugs and factors that control cardiac contractility and rhythm. A balance between structural and ionic components is required for the electromechanical impulse to propagate orderly across the myocardial cells. When structural heart disease or genetic or iatrogenic factors modify this interaction, the result can be the formation of a chaotic electrical activity or fibrillation which can affect either chamber of the heart, atria or ventricles. The atrial chaos or atrial fibrillation (AF) is defined as an erratic activation of the atria, causing an irregular heart rhythm at the ventricular level. AF remains the Achilles′ heel of cardiac rhythmology. Despite the overall advance in the treatment of the cardiac dysrhythmias with the introduction of radio frequency ablation, therapeutic options in AF have remained largely unchanged and aimed at controlling the heart rate and anticoagulation. New surgical and ablation techniques are being developed, while promising they are still extremely laborious and available only to a handful of patients. The limited success in the therapy of AF is in part due to our Poor understanding of its molecular pathophysiology. Advances in genetics and molecular biology will like1y give new insights into the development of the disease. Molecular research of AF has focused on two main fields, identification of the genes that playa role in the initiation of the disease and altered gene expression during the disease state. These studies are aimed at identifying not only the triggering factors in the acute form but also those that perpetuate the arrhythmia and convert it into a chronic form.
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References
Feinberg W.M, Blackshear J.L, Laupacis A, Kronmal R, Hart R.G. Prevalence, age distribution, and gender of patients with atrial fibrillation: analysis and implications. Arch Intern Med 1995; 155:469–73.
Wolf P.A, Abbot R.D, Kannel W.B. Atrial Fibrillation: a major contributor to stroke in the elderly: the Framingham Study. Arch Intern Med 1987; 147:1561–4.
Lok N.S, Lau C.P. Presentation and management of patients admitted with atrial fibrillation: A review of291 cases in a regional hospital. Int J Cardiol 1995; 48:271–278.
The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators: The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med 1990; 323:1505–1511.
Kopecky S.L, Gersh B.J, McGoon M.D, Whisnant J.P, Holmes D.R Jr, Ilstrup D.M, Frye R.L. The natural history oflone atrial fibrillation. A population-based study over three decades. N Engl J Med 1987; 317:669–674.
Brand F.N, Abbott R.D, Kannel W, Wolf P.A: Characteristics and prognosis of lone atrial fibrillation. 30-year follow-up in the Framingham study. JAMA 1985; 254:3449–3453
Atrial fibrillation Investigators: risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation: Analysis of pooled data from five randomized controlled trials. Arch Intern Med 1994; 154:1449-1457.
Girona J, Domingo A, Albert D, Casaldaliga J, Mont L, Brugada J, Brugada R. Fibrilacion auricular familiar. Rev. Esp. Cardiol 1997; 50:548–551.
Wolff, L. Familial auricular fibrillation. New Engl J Med 1943; 229:396.
Brugada R, Tapscott T, Czernuszewicz GZ, Marian AJ, Iglesias A, Mont L, Brugada J, Girona J, Domingo A, Bachinski LL, Roberts R. Identification of a genetic locus for familial atrial fibrillation. N Engl J Med 1997; 336:905–911.
Brugada R, Bachinski L, Hill R, Roberts R. Familial atrial fibrillation is a genetically heterogeneous disease. JACC, 1998; 31:349A.
Gruver E.J, Fatkin D, Dodds G.A, Kisslo J, Maron B.J, Seidman J.G, Seidman C.E. Familial hypertrophic cardiomyopathy and atrial fibrillation caused by Arg663His beta-cardiac myosin heavy chain mutation. Am J Cardiol. 1999; 83:13H–18H.
Richard P, Charron P, Leclercq C, Ledeuil C, Carrier L, Dubourg O, Desnos M, Bouhour J.B, Schwartz K, Daubert J.C, Komajda M, Hainque B. Homozygotes for a R869G mutation in the beta-myosin heavy chain gene have a severe form of familial hypertrophic cardiomyopathy. J Mol Cell Cardiol. 2000; 32:1575–83.
Ohkubo R, Nakagawa M, Higuchi I, Utatsu Y, Miyazato H, Atsuchi Y, Osame M. Familial skeletal myopathy with atrioventricular block. Intern Med. 1999; 38:856–60.
Ruchardt A, Eiseniohr H, Lydtin H. Myocardial involvement in carrier states for Duchenne muscular dystrophy. A rare cause of supraventricular arrhythmia. Dtsch Med Wochen sehr. 1998; 123:930–5.
Gillmore J.D, Booth D.R, Pepys M.B, Hawkins P.N. Hereditary cardiac amyloidosis associated with the transthyretin Ilel22 mutation in a white man. Heart 1999; 82:e2.
Stephan E, Ashoush R, Megarbane A, Kassab R, Salem N, Loiselet J, Bouvagnet P. Autosomal dominant Mendelian midline complex. Secundum atrial septal defect associated with cardiac and facial-thoracic defects. A familial case. Arch Mal Coeur Vaiss. 2000; 93:641–7.
Yamashita T, Hayami N, Ajiki K, Oikawa N, Sezaki K, Inoue M, Omata M, Murakawa Y. Is ACE gene polymorphism associated with lone atrial fibrillation? Jpn Heart J 1997; 38:637–41.
Nakai K, Itoh C, Miura Y, Hotta K, Musha T, Itoh T, Miyakawa T, Iwasaki R, Hiramori K. Deletion polymorphism of the angiotensin I-converting enzyme gene is associated with serum ACE concentration and increased risk for CAD in the Japanese. Circulation 1994; 90:2199–202.
Roden D.M, Lazzara R, Rosen M, Schwartz PJ, Towbin J, Vincent M. Multiple mechanisms in the long-QT syndrome. Current knowledge, gaps and future directions. Circulation. 1996; 94:1996–2012.
Chen Q, Kirsch G.E, Zhang D, Brugada R, Brugada J, Brugada P, Potenza D, Moya A, Borggrefe M, Breithardt G, Ortiz-Lopez R, Wang Z, Antzelevitch C, O′Brien R.E, SchulzeBahr E, Keating M.T, Towbin J.A, Wang Q. Genetic basis and molecular mechanisms for idiopathic ventricular fibrillation. Nature, 1998; 392:293–296.
Feng J, Yue L, Wang Z, Nattel S. Ionic mechanisms of regional action potential heterogeneity in the canine right atrium.Circ Res 1998; 83:541–51.
Morillo C.A, Klein G.J, Jones D.L, Guiraudon C.M. Chronic rapid atrial pacing. Structural, functional, and electrophysiological characteristics of a new model of sustained atrial fibrillation. Circulation 1995; 91:1588–95.
Van Wagoner D.R, Pond A.L, McCarthy P.M, Trimmer J.S, Nerbonne IM. Outward K+ current densities and K v 1.5 expression are reduced in chronic human atrial fibrillation. Circ. Res. 1997; 80:772–81.
Grammer J.B, Bosch R.F, Kuhlkamp V, Seipel L. Molecular remodeling of Kv4.3 potassium channels in human atrial fibrillation. J Cardiovasc Electrophysiol. 2000; 11:626–33.
Lai L.P, Su M.J, Lin J.L, Lin F.Y, Tsai C.H, Chen Y.S, Tseng Y.Z, Lien W.P, Huang S.K. Changes in the mRNA levels of delayed rectifier potassium channels in human atrial fibrillation. Cardiology. 1999; 92:248–55.
Goette A, Amdt M, Rocken C, Spiess A, Staack T, Geiler J.C, Huth C, Ansorge S, Klein H.U, Lendeekel U. Regulation of angiotensin II receptor subtypes during atrial fibrillation in humans. Circulation 2000; 101:2678–81.
Grammer J.B, Bosch R.F, Kuhlkamp V, Seipel L. Molecular and electrophysiological evidence for “ remodeling” of the L-type Ca2+ channel in persistent atrialfibrillatian in humans. Z Kardial. 2000; 89:IV23–9.
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Brugada, R., Roberts, R. (2001). Atrial Fibrillation. In: Doevendans, P.A., Wilde, A.A.M. (eds) Cardiovascular Genetics for Clinicians. Developments in Cardiovascular Medicine, vol 239. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-1019-1_16
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DOI: https://doi.org/10.1007/978-94-010-1019-1_16
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