- Email: [email protected]
Atrial cardiomyopathy—a not yet classified cardiomyopathy?
394
Letters to the Editor
Table 2 Hazard ratios of having a cardiovascular event or death from any cause depending on physical and mental perceived health. Cardiovascular events HR (95% CI) Physical perceived health First Tertile 1 Second tertile 0.63 (0.42; 0.94) Third tertile 0.50 (0.31; 0.80) Mental perceived health First Tertile 1 Second tertile 0.68 (0.44; 1.05) Third tertile 0.73 (0.49; 1.10)
Total mortality p value
HR (95% CI)
p value
0.022 0.004
1 0.58 (0.41; 0.82) 0.58 (0.39; 0.87)
0.002 0.007
0.085 0.135
1 1.01 (0.69; 1.49) 0.99 (0.69; 1.42)
0.951 0.943
Adjusted by age, gender, marital status, educational level and classical cardiovascular risk factors (smoking, diabetes, hypertension, hypercholesterolaemia).
The Kaplan–Meier survival curves for cardiovascular events and global mortality according to physical and mental perceived health tertiles are presented in Fig. 1. Multivariate analysis confirmed the independent association of physical perceived health with cardiovascular events and global mortality (Table 2). No association between mental health and cardiovascular events or global mortality was observed. Although we cannot explain how perceived health can influence adverse health events or mortality, it may reflect an awareness of subtle physiological changes that could more accurately define health status than an objective measure [5]. In order to understand the relationship between self-rated health and mortality the role of age, sex, psychosocial, emotional and socioeconomic factors has been previously studied [6,7]. After adjusting for these factors, our results agree with other authors who found that most of psychosocial factors do not
significantly influence the impact of self rated health on mortality [8,9]. Nevertheless, from our results, we can conclude that low physical perceived quality of life, assessed by SF-12, act as an independent risk factor for predicting cardiovascular events and total mortality. Consequently, SF-12 could be useful to identify individuals at high risk at an early stage. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology (Shewan and Coats 2010;144:1-2).
References [1] O'Loughlin C, Murphy NF, Conlon C, O'Donovan A, Ledwidge M, McDonald K. Quality of life predicts outcome in a heart failure disease management program. Int J Cardiol 2010;139:60–7. [2] Ware JE, Kosinski M, Keller A. A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Med Care 1996;34:220–33. [3] Grau M, Subirana I, Elosua R, Solanas P, Ramos R, Masia R, et al. Trends in cardiovascular risk factor prevalence (1995–2000–2005) in north-eastern Spain. Eur J Cardiovasc Prev Rehabil 2007;14:653–9. [4] Gandek B, Ware JE, Aaronson NK, Apolone G, Bjorner JB, Brazier JE, et al. Crossvalidation of item selection and scoring for the SF-12 Health Survey in nine countries: results from the IQOLA Project. International Quality of Life Assessment. J Clin Epidemiol 1998;51:1171–8. [5] Mossey JM, Shapiro E. Self-rated health: a predictor of mortality among the elderly. Am J Public Health 1982;72:800–8. [6] Heidrich J, Liese AD, Löwel H, Keil U. Self-rated health and its relation to all-cause and cardiovascular mortality in southern Germany. Results from the MONICA Augsburg cohort study 1984–1995. Ann Epidemiol 2002;12:338–45. [7] Fan VS, Au D, Heagerty P, Deyo RA, McDonell MB, Fihn SD. Validation of case–mix measures derived from self-reports of diagnoses and health. J Clin Epidemiol 2002;55:371–80. [8] Mackenbach J, Simon J, Looman C, Joung I. Self assesed health and mortality: could psychosocial factors explain the association? Int J Epidemiol 2002;31:1162–8. [9] Singh-Manoux A, Guéguen A, Martikainen P, Ferrie J, Marmot M, Shipley M. Selfrated health and mortality: short- and long-term associations in the Whitehall II Study. Psychosom Med 2007;69:138–43.
0167-5273/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2011.07.002
Atrial cardiomyopathy—a not yet classified cardiomyopathy? Mei Dong, Tong Liu, Guangping Li ⁎ Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China
a r t i c l e
i n f o
Article history: Received 28 June 2011 Accepted 3 July 2011 Available online 23 July 2011 Keywords: Atrial fibrillation Cardiomyopathy Structural remodeling Electrical remodeling
Cardiomyopathy is mainly defined by various degrees of impairment of cardiac function due to alterations of cardiac cellular phenotype in response to a variety of agents acting on cardiomyocytes. The present classification of cardiomyopathies [1] is all about ventricles, almost nothing referring to atria. Responsible for considerable population morbidity and mortality, atrial fibrillation (AF) has been extensively ⁎ Corresponding author. Tel.: +86 22 88328368; fax: +86 22 28261158. E-mail address: [email protected] (G. Li).
accepted as one of the most common sustained arrhythmias. However, with the evidences of impaired cardiac function, atrial remodeling, autonomic dysfunction and unfavorable prognosis of AF, there is an imperative need to better the understanding of the nature of AF. Hence, we hypothesize that AF may be a clinical manifestation of cardiomyopathy in atria which contributes to a new classification of cardiomyopathies. AF frequently coexists and shares mutual risk factors with heart failure (HF), and each has an adverse impact on the other [2–4]. Considerable studies have shown that AF can severely impair both cardiac systolic and diastolic function, especially in patients with known heart failure [5]. On the other hand, AF often occurs in the setting of heart failure [6]. HF leads to AF by affecting atrial structural processes which offer the favorable substrate for the initiation and perpetuation of AF. Mechanisms responsible for exacerbated cardiac dysfunction in AF patients are likely to involve changing in hemodynamics and neurohormone, and leading to dilated cardiomyopathy. Atrial remodeling including structural remodeling, electrical remodeling and neural remodeling, has been extensively accepted as the mainly interdependent mechanism for AF [7]. It emphasizes the changes in atrial structure and function, the alterations of atrial
Letters to the Editor
395
Fig. 1. The mechanisms and manifestations of structural remodeling in atrial fibrillation.
electrical and contractile properties that lead to AF [8], which in some sense reflects abnormalities of atrial myocytes from different aspects. Atrial fibrosis and dilation, and the changes in cellular ultrastructure and gap junction proteins [9–11] are hallmarks of the structural remodeling process which occurs more often in atria than in ventricles [12,13]. Structural remodeling aiming to prolong cellular viability results in the heterogeneity of the conduction tissue. The precise signaling processes involved in structural remodeling are unknown. However, TGF-ß1/SMAD pathway, the renin–angiotensin system, and inflammation and oxidative stress pathways appear to get involved in it [7,14] (Fig. 1). Electrical remodeling, represented by shortening of action potential and alteration in ionic channels offers an electrophysiological substrate for AF initiation [15–17], and finally maintains AF [18,19]. Altered intracellular calcium handling has double effects on atrial myocytes. Even though this change is a kind of cell self-protective reaction at the beginning, it eventually turns to electrical remodeling [20–22] leading to AF. Pharmacological interventions focusing on attenuating electrical remodeling have been proven to be beneficial to preventing AF [23]. Recently, several studies [24,25] have demonstrated that the intrinsic cardiac autonomic nervous system (ICANS) is able to initiate and maintain AF by affecting cardiac electrophysiological properties of the atrial myocardium which may facilitate the induction of AF. Alterations of sympathetic and parasympathetic nervous systems are implicated in
initiating paroxysmal AF [26]. Therefore, neural mechanism may serve as another remodeling mechanism for AF initiation and maintenance. Now, it seems suitable to say that atrial remodeling mechanism of AF, reflecting abnormalities of atrial myocytes, implies AF is a kind of cardiomyopathy in nature. Having noticed all of above findings, a new classification of cardiomyopathy, atrial cardiomyopathy has come into our picture. This classification relates not to the etiology of cardiomyopathy, but exclusively to the sites of cardiomyopathy. Furthermore, we merge atrial cardiomyopathy into one word, atriocardiomyopathy, which is concretely composed of primary atriocardiomyopathy, such as lone AF, with no obvious clinical cause, and secondary atriocardiomyopathy caused by organic heart diseases, such as coronary artery disease, pulmonary heart disease, heart failure and hypertension, etc. This new classification is of benefit beyond AF because of similarly pathological mechanisms among atrial arrhythmias. In conclusion, we propose a new classification of cardiomyopathies, atrial cardiomyopathy, as a basis of AF being considered a clinical manifestation of cardiomyopathy in atria. Therefore, we suggest the prefixes “atrio” and “ventriculo” should be conflated with the word “cardiomyopathy,” changing into “atriocardiomyopathy” and “ventriculocardiomyopathy” in order to distinguish the origins of cardiomyopathies (Fig. 2). However, much more studies are needed to verify this classification before it is widely accepted.
Fig. 2. A new classification of cardiomyopathies.
396
Letters to the Editor
The authors have declared no conflict of interest. This work was supported by National Natural Science Foundation of China (no. 30770863). The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology (Shewan and Coats 2010;144:1–2). References [1] Maron BJ, Towbin JA, Thiene G, et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2006;113:1807–16. [2] Everett TT, Olgin JE. Atrial fibrosis and the mechanisms of atrial fibrillation. Heart Rhythm 2007;4(3 Suppl):S24–7. [3] Wang TJ, Larson MG, Levy D, et al. Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study. Circulation 2003;107:2920–5. [4] Benjamin EJ, Wolf PA, D'Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation 1998;98:946–52. [5] Swedberg K, Olsson LG, Charlesworth A, et al. Prognostic relevance of atrial fibrillation in patients with chronic heart failure on long-term treatment with beta-blockers: results from COMET. Eur Heart J 2005;26:1303–8. [6] Maggioni AP, Latini R, Carson PE, et al. Valsartan reduces the incidence of atrial fibrillation in patients with heart failure: results from the Valsartan Heart Failure Trial (Val-HeFT). Am Heart J 2005;149:548–57. [7] Aldhoon B, Melenovský V, Peichl P, Kautzner J. New insights into mechanisms of atrial fibrillation. Physiol Res 2009;59:1–12. [8] Nattel S. New ideas about atrial fibrillation 50 years on. Nature 2002;415 (6868):219–26. [9] Yue L, Melnyk P, Gaspo R, Wang Z, Nattel S. Molecular mechanisms underlying ionic remodeling in a dog model of atrial fibrillation. Circ Res 1999;84:776–84. [10] Ausma J, Litjens N, Lenders MH, et al. Time course of atrial fibrillation-induced cellular structural remodeling in atria of the goat. J Mol Cell Cardiol 2001;33:2083–94. [11] Van der Velden HM, Ausma J, Rook MB, et al. Gap junctional remodeling in relation to stabilization of atrial fibrillation in the goat. Cardiovasc Res 2000;46:476–86.
0167-5273/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2011.07.003
[12] Burstein B, Libby E, Calderone A, Nattel S. Differential behaviors of atrial versus ventricular fibroblasts: a potential role for platelet-derived growth factor in atrial– ventricular remodeling differences. Circulation 2008;117:1630–41. [13] Tsai CT, Lai LP, Kuo KT, et al. Angiotensin II activates signal transducer and activators of transcription 3 via Rac1 in atrial myocytes and fibroblasts: implication for the therapeutic effect of statin in atrial structural remodeling. Circulation 2008;117:344–55. [14] Liu E, Yang S, Xu Z, Li J, Yang W, Li G. Angiotensin-(1–7) prevents atrial fibrosis and atrial fibrillation in long-term atrial tachycardia dogs. Regul Pept 2010;162:73–8. [15] Li G, Liu E, Liu T, et al. Atrial electrical remodeling in a canine model of sinus node dysfunction. Int J Cardiol 2011;146:32–6. [16] Yue L, Feng J, Gaspo R, Li GR, Wang Z, Nattel S. Ionic remodeling underlying action potential changes in a canine model of atrial fibrillation. Circ Res 1997;81:512–25. [17] Van Wagoner DR. Molecular basis of atrial fibrillation: a dream or a reality? J Cardiovasc Electrophysiol 2003;14:667–9. [18] Neuberger HR, Schotten U, Blaauw Y, et al. Chronic atrial dilation, electrical remodeling, and atrial fibrillation in the goat. J Am Coll Cardiol 2006;47:644–53. [19] Neuberger HR, Schotten U, Verheule S, et al. Development of a substrate of atrial fibrillation during chronic atrioventricular block in the goat. Circulation 2005;111:30–7. [20] Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation 1995;92:1954–68. [21] Gaspo R, Bosch RF, Bou-Abboud E, Nattel S. Tachycardia-induced changes in Na+ current in a chronic dog model of atrial fibrillation. Circ Res 1997;81:1045–52. [22] Elvan A, Wylie K, Zipes DP. Pacing-induced chronic atrial fibrillation impairs sinus node function in dogs. Electrophysiological remodeling. Circulation 1996;94:2953–60. [23] Liu E, Xu Z, Li J, Yang S, Yang W, Li G. Enalapril, irbesartan, and angiotensin-(1–7) prevent atrial tachycardia-induced ionic remodeling. Int J Cardiol 2011;146:364–70. [24] Po SS, Scherlag BJ, Yamanashi WS, et al. Experimental model for paroxysmal atrial fibrillation arising at the pulmonary vein-atrial junctions. Heart Rhythm 2006;3:201–18. [25] Zhou J, Scherlag BJ, Edwards J, Jackman WM, Lazzara R, Po SS. Gradients of atrial refractoriness and inducibility of atrial fibrillation due to stimulation of ganglionated plexi. J Cardiovasc Electrophysiol 2007;18:83–90. [26] Goldberger AL, Pavelec RS. Vagally-mediated atrial fibrillation in dogs: conversion with bretylium tosylate. Int J Cardiol 1986;13:47–55.
Letters to the Editor
Table 2 Hazard ratios of having a cardiovascular event or death from any cause depending on physical and mental perceived health. Cardiovascular events HR (95% CI) Physical perceived health First Tertile 1 Second tertile 0.63 (0.42; 0.94) Third tertile 0.50 (0.31; 0.80) Mental perceived health First Tertile 1 Second tertile 0.68 (0.44; 1.05) Third tertile 0.73 (0.49; 1.10)
Total mortality p value
HR (95% CI)
p value
0.022 0.004
1 0.58 (0.41; 0.82) 0.58 (0.39; 0.87)
0.002 0.007
0.085 0.135
1 1.01 (0.69; 1.49) 0.99 (0.69; 1.42)
0.951 0.943
Adjusted by age, gender, marital status, educational level and classical cardiovascular risk factors (smoking, diabetes, hypertension, hypercholesterolaemia).
The Kaplan–Meier survival curves for cardiovascular events and global mortality according to physical and mental perceived health tertiles are presented in Fig. 1. Multivariate analysis confirmed the independent association of physical perceived health with cardiovascular events and global mortality (Table 2). No association between mental health and cardiovascular events or global mortality was observed. Although we cannot explain how perceived health can influence adverse health events or mortality, it may reflect an awareness of subtle physiological changes that could more accurately define health status than an objective measure [5]. In order to understand the relationship between self-rated health and mortality the role of age, sex, psychosocial, emotional and socioeconomic factors has been previously studied [6,7]. After adjusting for these factors, our results agree with other authors who found that most of psychosocial factors do not
significantly influence the impact of self rated health on mortality [8,9]. Nevertheless, from our results, we can conclude that low physical perceived quality of life, assessed by SF-12, act as an independent risk factor for predicting cardiovascular events and total mortality. Consequently, SF-12 could be useful to identify individuals at high risk at an early stage. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology (Shewan and Coats 2010;144:1-2).
References [1] O'Loughlin C, Murphy NF, Conlon C, O'Donovan A, Ledwidge M, McDonald K. Quality of life predicts outcome in a heart failure disease management program. Int J Cardiol 2010;139:60–7. [2] Ware JE, Kosinski M, Keller A. A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Med Care 1996;34:220–33. [3] Grau M, Subirana I, Elosua R, Solanas P, Ramos R, Masia R, et al. Trends in cardiovascular risk factor prevalence (1995–2000–2005) in north-eastern Spain. Eur J Cardiovasc Prev Rehabil 2007;14:653–9. [4] Gandek B, Ware JE, Aaronson NK, Apolone G, Bjorner JB, Brazier JE, et al. Crossvalidation of item selection and scoring for the SF-12 Health Survey in nine countries: results from the IQOLA Project. International Quality of Life Assessment. J Clin Epidemiol 1998;51:1171–8. [5] Mossey JM, Shapiro E. Self-rated health: a predictor of mortality among the elderly. Am J Public Health 1982;72:800–8. [6] Heidrich J, Liese AD, Löwel H, Keil U. Self-rated health and its relation to all-cause and cardiovascular mortality in southern Germany. Results from the MONICA Augsburg cohort study 1984–1995. Ann Epidemiol 2002;12:338–45. [7] Fan VS, Au D, Heagerty P, Deyo RA, McDonell MB, Fihn SD. Validation of case–mix measures derived from self-reports of diagnoses and health. J Clin Epidemiol 2002;55:371–80. [8] Mackenbach J, Simon J, Looman C, Joung I. Self assesed health and mortality: could psychosocial factors explain the association? Int J Epidemiol 2002;31:1162–8. [9] Singh-Manoux A, Guéguen A, Martikainen P, Ferrie J, Marmot M, Shipley M. Selfrated health and mortality: short- and long-term associations in the Whitehall II Study. Psychosom Med 2007;69:138–43.
0167-5273/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2011.07.002
Atrial cardiomyopathy—a not yet classified cardiomyopathy? Mei Dong, Tong Liu, Guangping Li ⁎ Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China
a r t i c l e
i n f o
Article history: Received 28 June 2011 Accepted 3 July 2011 Available online 23 July 2011 Keywords: Atrial fibrillation Cardiomyopathy Structural remodeling Electrical remodeling
Cardiomyopathy is mainly defined by various degrees of impairment of cardiac function due to alterations of cardiac cellular phenotype in response to a variety of agents acting on cardiomyocytes. The present classification of cardiomyopathies [1] is all about ventricles, almost nothing referring to atria. Responsible for considerable population morbidity and mortality, atrial fibrillation (AF) has been extensively ⁎ Corresponding author. Tel.: +86 22 88328368; fax: +86 22 28261158. E-mail address: [email protected] (G. Li).
accepted as one of the most common sustained arrhythmias. However, with the evidences of impaired cardiac function, atrial remodeling, autonomic dysfunction and unfavorable prognosis of AF, there is an imperative need to better the understanding of the nature of AF. Hence, we hypothesize that AF may be a clinical manifestation of cardiomyopathy in atria which contributes to a new classification of cardiomyopathies. AF frequently coexists and shares mutual risk factors with heart failure (HF), and each has an adverse impact on the other [2–4]. Considerable studies have shown that AF can severely impair both cardiac systolic and diastolic function, especially in patients with known heart failure [5]. On the other hand, AF often occurs in the setting of heart failure [6]. HF leads to AF by affecting atrial structural processes which offer the favorable substrate for the initiation and perpetuation of AF. Mechanisms responsible for exacerbated cardiac dysfunction in AF patients are likely to involve changing in hemodynamics and neurohormone, and leading to dilated cardiomyopathy. Atrial remodeling including structural remodeling, electrical remodeling and neural remodeling, has been extensively accepted as the mainly interdependent mechanism for AF [7]. It emphasizes the changes in atrial structure and function, the alterations of atrial
Letters to the Editor
395
Fig. 1. The mechanisms and manifestations of structural remodeling in atrial fibrillation.
electrical and contractile properties that lead to AF [8], which in some sense reflects abnormalities of atrial myocytes from different aspects. Atrial fibrosis and dilation, and the changes in cellular ultrastructure and gap junction proteins [9–11] are hallmarks of the structural remodeling process which occurs more often in atria than in ventricles [12,13]. Structural remodeling aiming to prolong cellular viability results in the heterogeneity of the conduction tissue. The precise signaling processes involved in structural remodeling are unknown. However, TGF-ß1/SMAD pathway, the renin–angiotensin system, and inflammation and oxidative stress pathways appear to get involved in it [7,14] (Fig. 1). Electrical remodeling, represented by shortening of action potential and alteration in ionic channels offers an electrophysiological substrate for AF initiation [15–17], and finally maintains AF [18,19]. Altered intracellular calcium handling has double effects on atrial myocytes. Even though this change is a kind of cell self-protective reaction at the beginning, it eventually turns to electrical remodeling [20–22] leading to AF. Pharmacological interventions focusing on attenuating electrical remodeling have been proven to be beneficial to preventing AF [23]. Recently, several studies [24,25] have demonstrated that the intrinsic cardiac autonomic nervous system (ICANS) is able to initiate and maintain AF by affecting cardiac electrophysiological properties of the atrial myocardium which may facilitate the induction of AF. Alterations of sympathetic and parasympathetic nervous systems are implicated in
initiating paroxysmal AF [26]. Therefore, neural mechanism may serve as another remodeling mechanism for AF initiation and maintenance. Now, it seems suitable to say that atrial remodeling mechanism of AF, reflecting abnormalities of atrial myocytes, implies AF is a kind of cardiomyopathy in nature. Having noticed all of above findings, a new classification of cardiomyopathy, atrial cardiomyopathy has come into our picture. This classification relates not to the etiology of cardiomyopathy, but exclusively to the sites of cardiomyopathy. Furthermore, we merge atrial cardiomyopathy into one word, atriocardiomyopathy, which is concretely composed of primary atriocardiomyopathy, such as lone AF, with no obvious clinical cause, and secondary atriocardiomyopathy caused by organic heart diseases, such as coronary artery disease, pulmonary heart disease, heart failure and hypertension, etc. This new classification is of benefit beyond AF because of similarly pathological mechanisms among atrial arrhythmias. In conclusion, we propose a new classification of cardiomyopathies, atrial cardiomyopathy, as a basis of AF being considered a clinical manifestation of cardiomyopathy in atria. Therefore, we suggest the prefixes “atrio” and “ventriculo” should be conflated with the word “cardiomyopathy,” changing into “atriocardiomyopathy” and “ventriculocardiomyopathy” in order to distinguish the origins of cardiomyopathies (Fig. 2). However, much more studies are needed to verify this classification before it is widely accepted.
Fig. 2. A new classification of cardiomyopathies.
396
Letters to the Editor
The authors have declared no conflict of interest. This work was supported by National Natural Science Foundation of China (no. 30770863). The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology (Shewan and Coats 2010;144:1–2). References [1] Maron BJ, Towbin JA, Thiene G, et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2006;113:1807–16. [2] Everett TT, Olgin JE. Atrial fibrosis and the mechanisms of atrial fibrillation. Heart Rhythm 2007;4(3 Suppl):S24–7. [3] Wang TJ, Larson MG, Levy D, et al. Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study. Circulation 2003;107:2920–5. [4] Benjamin EJ, Wolf PA, D'Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation 1998;98:946–52. [5] Swedberg K, Olsson LG, Charlesworth A, et al. Prognostic relevance of atrial fibrillation in patients with chronic heart failure on long-term treatment with beta-blockers: results from COMET. Eur Heart J 2005;26:1303–8. [6] Maggioni AP, Latini R, Carson PE, et al. Valsartan reduces the incidence of atrial fibrillation in patients with heart failure: results from the Valsartan Heart Failure Trial (Val-HeFT). Am Heart J 2005;149:548–57. [7] Aldhoon B, Melenovský V, Peichl P, Kautzner J. New insights into mechanisms of atrial fibrillation. Physiol Res 2009;59:1–12. [8] Nattel S. New ideas about atrial fibrillation 50 years on. Nature 2002;415 (6868):219–26. [9] Yue L, Melnyk P, Gaspo R, Wang Z, Nattel S. Molecular mechanisms underlying ionic remodeling in a dog model of atrial fibrillation. Circ Res 1999;84:776–84. [10] Ausma J, Litjens N, Lenders MH, et al. Time course of atrial fibrillation-induced cellular structural remodeling in atria of the goat. J Mol Cell Cardiol 2001;33:2083–94. [11] Van der Velden HM, Ausma J, Rook MB, et al. Gap junctional remodeling in relation to stabilization of atrial fibrillation in the goat. Cardiovasc Res 2000;46:476–86.
0167-5273/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2011.07.003
[12] Burstein B, Libby E, Calderone A, Nattel S. Differential behaviors of atrial versus ventricular fibroblasts: a potential role for platelet-derived growth factor in atrial– ventricular remodeling differences. Circulation 2008;117:1630–41. [13] Tsai CT, Lai LP, Kuo KT, et al. Angiotensin II activates signal transducer and activators of transcription 3 via Rac1 in atrial myocytes and fibroblasts: implication for the therapeutic effect of statin in atrial structural remodeling. Circulation 2008;117:344–55. [14] Liu E, Yang S, Xu Z, Li J, Yang W, Li G. Angiotensin-(1–7) prevents atrial fibrosis and atrial fibrillation in long-term atrial tachycardia dogs. Regul Pept 2010;162:73–8. [15] Li G, Liu E, Liu T, et al. Atrial electrical remodeling in a canine model of sinus node dysfunction. Int J Cardiol 2011;146:32–6. [16] Yue L, Feng J, Gaspo R, Li GR, Wang Z, Nattel S. Ionic remodeling underlying action potential changes in a canine model of atrial fibrillation. Circ Res 1997;81:512–25. [17] Van Wagoner DR. Molecular basis of atrial fibrillation: a dream or a reality? J Cardiovasc Electrophysiol 2003;14:667–9. [18] Neuberger HR, Schotten U, Blaauw Y, et al. Chronic atrial dilation, electrical remodeling, and atrial fibrillation in the goat. J Am Coll Cardiol 2006;47:644–53. [19] Neuberger HR, Schotten U, Verheule S, et al. Development of a substrate of atrial fibrillation during chronic atrioventricular block in the goat. Circulation 2005;111:30–7. [20] Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation 1995;92:1954–68. [21] Gaspo R, Bosch RF, Bou-Abboud E, Nattel S. Tachycardia-induced changes in Na+ current in a chronic dog model of atrial fibrillation. Circ Res 1997;81:1045–52. [22] Elvan A, Wylie K, Zipes DP. Pacing-induced chronic atrial fibrillation impairs sinus node function in dogs. Electrophysiological remodeling. Circulation 1996;94:2953–60. [23] Liu E, Xu Z, Li J, Yang S, Yang W, Li G. Enalapril, irbesartan, and angiotensin-(1–7) prevent atrial tachycardia-induced ionic remodeling. Int J Cardiol 2011;146:364–70. [24] Po SS, Scherlag BJ, Yamanashi WS, et al. Experimental model for paroxysmal atrial fibrillation arising at the pulmonary vein-atrial junctions. Heart Rhythm 2006;3:201–18. [25] Zhou J, Scherlag BJ, Edwards J, Jackman WM, Lazzara R, Po SS. Gradients of atrial refractoriness and inducibility of atrial fibrillation due to stimulation of ganglionated plexi. J Cardiovasc Electrophysiol 2007;18:83–90. [26] Goldberger AL, Pavelec RS. Vagally-mediated atrial fibrillation in dogs: conversion with bretylium tosylate. Int J Cardiol 1986;13:47–55.