Biomarkers and atrial fibrillation: A new paradigm for assessing the progression of left atrial endocardial remodelling

Philippe Chevalier, Alina Scridon

Hospices Civils de Lyon, H?pital Louis Pradel, Service de Rythmologie, Lyon, France.
University of Medicine and Pharmacy of Targu Mures, Targu Mures, Romania.

DOI: 10.4236/ojcd.2012.22004                

Abstract

Atrial fibrillation is a heterogeneous disorder that is usually characterized by paroxysmal onset, particularly in patients without structural heart disease. Defining biological markers of atrial remodelling would help identify patients at high risk who would benefit most from prophylactic treatment and careful monitoring. Biomarkers of atrial fibrillation progression would be helpful for following patients that present with asymptomatic atrial fibrillation. Notably, the roles of such markers in the pathophysiology of atrial fibrillation must be determined. Some markers may indicate the presence, complications or progression of the disease, while others may be involved in key pathological processes and thus represent novel therapeutic targets. Although a number of markers have been reported as potential predictors of paroxysmal atrial fibrillation progression towards persistent arrhythmia, their usefulness and clinical value need further validation. This report reviews several newly identified markers of atrial fibrillation progression.

Keywords

Atrial Fibrillation; Biomarkers; Progression

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Wyse, D.G. and Gersh, B.J. (2004) Atrial fibrillation: A perspective: Thinking inside and outside the box. Circulation, 109, 3089-3095. http://circ.ahajournals.org/content/109/25/3089.full.pdf+html doi:10.1161/01.CIR.0000132611.01101.DC
[2]	Feinberg, W.M., Blackshear, J.L., Laupacis, A., Kronmal, R. and Hart, R.G. (1995) Prevalence, age distribution, and gender of patients with atrial fibrillation: analysis and implications. Archives of Internal Medicine, 155, 469-473. http://www.ncbi.nlm.nih.gov/pubmed/7864703 doi:10.1001/archinte.1995.00430050045005
[3]	Go, A.S., Hylek, E.M., Phillips, K.A., Chang, Y., Henault, L.E., Selby, J.V. and Singer, D.E. (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. Journal of the American Medical Association, 285, 2370-2375. http://jama.ama-assn.org/content/285/18/2370.full.pdf+html doi:10.1001/jama.285.18.2370
[4]	Chugh, S.S., Blackshear, J.L., Shen, W.K., Hammill, S.C. and Gersh, B.J. (2001) Epidemiology and natural history of atrial fibrillation: clinical implications. Journal of the American College of Cardiology, 37, 371-378. http://content.onlinejacc.org/cgi/reprint/37/2/371.pdf doi:10.1016/S0735-1097(00)01107-4
[5]	Wijffels, M.C., Kirchhof, C.J., Dorland, R. and Allessie, M.A. (1995) Atrial fibrillation begets atrial fibrillation: A study in awake chronically instrumented goats. Circulation, 92, 1954-1968. http://circ.ahajournals.org/content/92/7/1954.full
[6]	Allessie, M., Ausma, J. and Schotten, U. (2002) Electrical, contractile and structural remodeling during atrial fibrillation. Cardiovascular Research, 54, 230-246. http://cardiovascres.oxfordjournals.org/content/54/2/230.full doi:10.1016/S0008-6363(02)00258-4
[7]	de Vos, C.B., Pisters, R., Nieuwlaat, R., Prins, M.H., Tieleman, R.G., Coelen, R.J.S., van den Heijkant, A.C., Allessie, M.A. and Crijns, H.J.G.M. (2010) Progression from paroxysmal to persistent atrial fibrillation: clinical correlates and prognosis. Journal of the American College of Cardiology, 55, 725-731. http://content.onlinejacc.org/cgi/content/full/55/8/725 doi:10.1016/j.jacc.2009.11.040
[8]	Jahangir, A., Lee, V., Friedman, P.A., Trusty, J.M., Hodge, D.O., Kopecky, S.L., Packer, D.L., Hammill, S.C., Shen, W.K. and Gersh, B.J. (2007) Long-term progression and outcomes with aging in patients with lone atrial fibrillation: A 30-year follow-up study. Circulation, 115, 3050-3056. http://circ.ahajournals.org/content/115/24/3050.full doi:10.1161/CIRCULATIONAHA.106.644484
[9]	Komatsu, T., Nakamura, S., Saitou, E., Kobayashi, T., Kumagai, K. and Okumura, K. (2000) Long-term efficacy of antiarrhythmic drugs in the prevention of paroxysmal atrial fibrillation; significance of suffering period. Japanese Journal of Electrocardiology, 1, 27-32.
[10]	Kannel, W.B., Abbott, R.D., Savage, D.D. and McNamara, P.M. (1982) Epidemiologic features of chronic atrial fibrillation: The framingham study. New England Journal of Medicine, 306, 1018-1022. http://www.ncbi.nlm.nih.gov/pubmed/7062992 doi:10.1056/NEJM198204293061703
[11]	Abe, Y., Fukunami, M., Yamada, T., Ohmori, M., Shimonagata, T., Kumagai, K., Kim, J., Sanada, S., Hori, M. and Hoki, N. (1997) Prediction of transition to chronic atrial fibrillation in patients with paroxysmal atrial fibrillation by signal-averaged electrocardiography. Circulation, 96, 2612-2616. http://circ.ahajournals.org/content/96/8/2612.long
[12]	Kerr, C.R., Humphries, K.H., Talajic, M., Klein, G.J., Connolly, S.J., Green, M., Boone, J., Sheldon, R., Dorian, P. and Newman, D. (2005) Progression to chronic atrial fibrillation after the initial diagnosis of paroxysmal atrial fibrillation: Results from the Canadian Registry of Atrial Fibrillation. American Heart Journal, 149, 489-496. http://www.medscape.com/viewarticle/502666 doi:10.1016/j.ahj.2004.09.053
[13]	Henningsen, K.M., Therkelsen, S.K., Johansen, J.S., Bruunsgaard, H. and Svendsen, J.H. (2009) Plasma YKL-40, a new biomarker for atrial fibrillation? Europace, 11, 1032-1036. http://europace.oxfordjournals.org/content/11/8/1032.full doi:10.1093/europace/eup103
[14]	Chung, M.K., Martin, D.O., Sprecher, D., Wazni, O., Kanderian, A., Carnes, C.A., Bauer, J.A., Tchou, P.J., Niebauer, M.J., Natale, A. and van Wagoner, D.R. (2001) C-reactive protein elevation in patients with atrial arrhythmias : Inflammatory mechanisms and persistence of atrial fibrillation. Circulation, 104, 2886-2891. http://circ.ahajournals.org/content/104/24/2886.full doi:10.1161/hc4901.101760
[15]	Conway, D.S., Buggins, P., Hughes, E. and Lip, G.Y. (2004) Relationship of interleukin-6 and C-reactive protein to the prothrombotic state in chronic atrial fibrillation. Journal of the American College of Cardiology, 43, 2075-2082. http://content.onlinejacc.org/cgi/content/full/43/11/2075 doi:10.1016/j.jacc.2003.11.062
[16]	Van Wagoner, D.R. (2008) Oxidative stress and inflammation in atrial fibrillation: Role in pathogenesis and potential as a therapeutic target. Journal of Cardiovascular Pharmacology, 52, 306-313. http://www.ncbi.nlm.nih.gov/pubmed/18791466 doi:10.1097/FJC.0b013e31817f9398
[17]	Liuba, I., Ahlmroth, H., Jonasson, L., Englund, A., Safstrom, K. and Walfridsson, H. (2008) Source of inflammatory markers in patients with atrial fibrillation. Europace, 10, 848-853. http://europace.oxfordjournals.org/content/10/7/848.full doi:10.1093/europace/eun111
[18]	Ellinor, P.T., Low, A., Patton, K.K., Shea, M.A. and MacRae, C.A. (2006) C-reactive protein in lone atrial fibrillation. American Journal of Cardiology, 97, 1346-1350. http://www.sciencedirect.com/science/article/pii/S0002914906001585 doi:10.1016/j.amjcard.2005.11.052
[19]	Roldan, V., Marin, F., Blann, A.D., Garcia, A., Marco, P., Sogorb, F. and Lip, G.Y. (2003) Interleukin-6, endothelial activation and thrombogenesis in chronic atrial fibrillation. European Heart Journal, 24, 1373-1380. http://eurheartj.oxfordjournals.org/content/24/14/1373.full doi:10.1016/S0195-668X(03)00239-2
[20]	Scridon, A., Morel, E., Nonin-Babary, E., Girerd, N., Fernandez, C., and Chevalier, P. (2012) Increased intracardiac vascular endothelial growth factor levels in patients with paroxysmal, but not persistent atrial fibrillation. Europace, in press. http://europace.oxfordjournals.org/content/early/2012/02/02/europace.eur418.full
[21]	Li, J., Hampton, T., Morgan, J.P. and Simons, M. (1997) Stretch-induced VEGF expression in the heart. Journal of Clinical Investigations, 100, 18-24. http://www.jci.org/articles/view/119510
[22]	Wong, A.K., Marais, H.J., Jutzy, K., Capestany, G.A. and Marais, G.E. (1991) Isolated atrial infarction in a patient with single vessel disease of the sinus node artery. Chest, 100, 255-256. http://chestjournal.chestpubs.org/content/100/1/255.full.pdf+html doi:10.1378/chest.100.1.255
[23]	Thijssen, V.L., van der Velden, H.M., van Ankeren, E.P., Ausma, J., Allessie, M.A., Borgers, M., van Eys, G.J. and Jongsma, H.J. (2002) Analysis of altered gene expression during sustained atrial fibrillation in the goat. Cardiovascular Research, 54, 427-437. http://cardiovascres.oxfordjournals.org/content/54/2/427.full doi:10.1016/S0008-6363(02)00260-2
[24]	Freeman, M.R., Scheck, F.X., Gagnon, M.L., Corless, C., Soker, S., Niknejad, K., Peoples, G.E. and Klagsbrun, M. (1995) Peripheral blood T-lymphocytes and lymphocytes infiltrating human cancers express vascular endothelial growth factor: A potential role for T cells in angiogenesis. Cancer Research, 55, 4140-4145. http://cancerres.aacrjournals.org/content/55/18/4140.full.pdf
[25]	Gaudry, M., Bregerie, O., Andrieu, V., El Benna, J., Pocidalo, M.A. and Hakim, J. (1997) Intracellular pool of vascular endothelial growth factor in human neutrophils. Blood, 90, 4153-4161. http://bloodjournal.hematologylibrary.org/content/90/10/4153.full.pdf
[26]	Mohle, R., Green, D., Moore, M.A.S., Nachman, R.L. and Rafii, S. (1997) Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. Proceedings of the National Academy of Sciences USA, 94, 663-668. http://www.ncbi.nlm.nih.gov/pubmed/9012841 doi:10.1073/pnas.94.2.663
[27]	Seko, Y., Seko, Y., Takahashi, N., Shibuya, M. and Yazaki, Y. (1999) Pulsatile stretch stimulates vascular endothelial growth factor (VEGF) secretion by cultured rat cardiac myocytes. Biochemical and Biophysical Research Communications, 254, 462-465. http://www.sciencedirect.com/science/article/pii/S0006291X98999697 doi:10.1006/bbrc.1998.9969
[28]	Kallergis, E.M., Manios, E.G., Kanoupakis, E.M., Mavrakis, H.E., Arfanakis, D.A., Maliaraki, N.E., Lathourakis, C.E., Chlouverakis, G.I. and Vardas, P.E. (2008) Extracellular matrix alterations in patients with paroxysmal and persistent atrial fibrillation: biochemical assessment of collagen type-I turnover. Journal of the American College of Cardiology, 52, 211-215. http://content.onlinejacc.org/cgi/content/full/52/3/211
[29]	Gramley, F., Lorenzena, J., Koellensperger, E., Kettering, K., Weiss, C. and Munzel, T. (2010) Atrial fibrosis and atrial fibrillation: The role of the TGF-β1 signaling pathway. International Journal of Cardiology, 143, 405-413. http://www.sciencedirect.com/science/article/pii/S0167527309003969 doi:10.1016/j.ijcard.2009.03.110
[30]	Chaudhary, N.I., Roth, G.J., Hilberg, F., Müller-Quernheim, J., Prasse, A., Zissel, G., Schnapp, A. and Park, J.E. (2007) Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis. European Respiratory Journal, 29, 976-985. http://erj.ersjournals.com/content/29/5/976.full doi:10.1183/09031936.00152106
[31]	Hamada, N., Kuwano, K., Yamada, M., Hagimoto, N., Hiasa, K., Egashira, K., Nakashima, N., Maeyama, T., Yoshimi, M. and Nakanishi, Y. (2005) Anti-vascular endothelial growth factor gene therapy attenuates lung injury and fibrosis in mice. Journal of Immunology, 175, 1224-1231. http://www.jimmunol.org/content/175/2/1224.full
[32]	Motomura, Y., Kanbayashi, H., Khan, W.I., Deng, Y., Blennerhassett, P.A., Margetts, P.J., Gauldie, J., Egashira, K. and Collins, S.M. (2005) The gene transfer of soluble VEGF type I receptor (Flt-1) attenuates peritoneal fibrosis formation in mice but not soluble TGF-beta type II receptor gene transfer. American Journal of Physiology: Gastrointestinal and Liver Physiology, 288, G143-G150. http://ajpgi.physiology.org/content/288/1/G143.full
[33]	Jahangir, A., Munger, T.M., Packer, D.L. and Crijns, H.J.G.M. (2001) Atrial fibrillation. In: Podrid, P.J. and Kowey, P.R. Eds., Cardiac Arrhythmia: Mechanisms, Diagnosis, and Management, 2nd Edition, Lippincott Williams & Wilkins, Philadelphia, 457-499.
[34]	Tsang, T.S., Gersh, B.J., Appleton, C.P., Tajik, A.J., Barnes, M.E., Bailey, K.R., Oh, J.K., Leibson, C., Montgomery, S.C. and Seward, J.B. (2002) Left ventricular diastolic dysfunction as a predictor of the first diagnosed nonvalvular atrial fibrillation in 840 elderly men and women. Journal of the American College of Cardiology, 40, 1636-1644. http://content.onlinejacc.org/cgi/content/full/40/9/1636 doi:10.1016/S0735-1097(02)02373-2
[35]	Wang, T.J., Parise, H., Levy, D., D’Agostino, R.B. Sr., Wolf, P.A., Vasan, R.S. and Benjamin, E.J. (2004) Obesity and the risk of new-onset atrial fibrillation. Journal of the American Medical Association, 292, 2471-2477. http://jama.ama-assn.org/content/292/20/2471.full doi:10.1001/jama.292.20.2471
[36]	Gami, A.S., Pressman, G., Caples, S.M., Kanagala, R., Gard, J.J., Davison, D.E., Malouf, J.F., Ammash, N.M., Friedman, P.A. and Somers, V.K. (2004) Association of atrial fibrillation and obstructive sleep apnea. Circulation, 110, 364-367. http://circ.ahajournals.org/content/110/4/364.full doi:10.1161/01.CIR.0000136587.68725.8E
[37]	Verdecchia, P., Reboldi, G., Gattobigio, R., Bentivoglio, M., Borgioni, C., Angeli, F., Carluccio, E., Sardone, M.G. and Porcellati, C. (2003) Atrial fibrillation in hypertension: Predictors and outcome. Hypertension, 41, 218-223. http://hyper.ahajournals.org/content/41/2/218.full
[38]	Aviles, R.J., Martin, D.O., Apperson-Hansen, C., Houghtaling, P.L., Rautaharju, P., Kronmal, R.A., Tracy, R.P., Van Wagoner, D.R., Psaty, B.M., Lauer, M.S. and Chung, M.K. (2003) Inflammation as a risk factor for atrial fibrillation. Circulation, 108, 3006-3010. http://circ.ahajournals.org/content/108/24/3006.full doi:10.1161/01.CIR.0000103131.70301.4F
[39]	Nieuwlaat, R., Prins, M.H., Le Heuzey, J.Y., Vardas, P.E., Aliot, E., Santini, M., Cobbe, S.M., Widdershoven, J.W.M.G., Baur, L.H., Levy, S. and Crijns, H.J.G.M. (2008) Prognosis, disease progression, and treatment of atrial fibrillation patients during 1 year: Follow-up of the Euro Heart Survey on Atrial Fibrillation. European Heart Journal, 29, 1181-1189. http://eurheartj.oxfordjournals.org/content/29/9/1181.full doi:10.1093/eurheartj/ehn139