New and Emerging Biomarkers in Left Ventricular Systolic Dysfunction—Insight into Dilated Cardiomyopathy

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Abstract

Dilated cardiomyopathy (DCM) is characterized by deteriorating cardiac performance, impaired contraction and dilation of the left ventricle (or both ventricles). Blood markers—known as “biomarkers”—allow insight into underlying pathophysiologic mechanisms and biologic pathways while predicting outcomes and guiding heart failure management and/or therapies. In this review, we provide an alternative approach to conceptualize heart failure biomarkers: the cardiomyocyte, its surrounding microenvironment, and the macroenvironment, integrating these entities which may impact cellular processes involved in the pathogenesis and/or propagation of DCM. Newer biomarkers of left ventricular systolic dysfunction can be categorized under: (a) myocyte stress and stretch, (b) myocyte apoptosis, (c) cardiac interstitium, (d) inflammation, (e) oxidative stress, (f) cardiac energetics, (g) neurohormones, and (h) renal biomarkers. Biomarkers provide insight into the pathogenesis of DCM while predicting and potentially providing prognostic information in these patients with heart failure.

Keywords

Biomarkers Dilated cardiomyopathy Heart failure 
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References

  1. 1.
    Maron, B. J., Towbin, J. A., Thiene, G., Antzelevitch, C., Corrado, D., Arnett, D., Moss, A. J., Seidman, C. E., Young, J. B., American Heart Association, Council on Clinical Cardiology, Heart Failure, Transplantation Committe, Quality of Care, Outcomes Research, Functional Genomics, Translational Biology Interdisciplinary Working Group, & Council on Epidemiology Prevention. (2006). 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, 113, 1807–1816.PubMedCrossRefGoogle Scholar
  2. 2.
    Richardson, P., McKenna, W., Bristow, M., Maisch, B., Mautner, B., O'Connell, J., Olsen, E., Thiene, G., Goodwin, J., Gyarfas, I., Martin, I., & Nordet, P. (1996). Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of Cardiomyopathies. Circulation, 93, 841–842.PubMedCrossRefGoogle Scholar
  3. 3.
    Lang, R. M., Bierig, M., Devereux, R. B., Flachskampf, F. A., Foster, E., Pellikka, P. A., Picard, M. H., Roman, M. J., Seward, J., Shanewise, J. S., Solomon, S. D., Spencer, K. T., Sutton, M. S., Stewart, W. J., Chamber Quantification Writing Group, American Society of Echocardiography's Guidelines, Standards Committee, & European Association of Echocardiography. (2005). Recommendations for chamber quantification: A report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association Of Echocardiography, a branch of the European Society Of Cardiology. Journal of the American Society of Echocardiography, 18, 1440–1463.PubMedCrossRefGoogle Scholar
  4. 4.
    Davies, M. J., & McKenna, W. J. (1994). Dilated cardiomyopathy: An introduction to pathology and pathogenesis. British Heart Journal, 72, S24.PubMedCrossRefGoogle Scholar
  5. 5.
    Maisel, A. S., Krishnaswamy, P., Nowak, R. M., McCord, J., Hollander, J. E., Duc, P., Omland, T., Storrow, A. B., Abraham, W. T., Wu, A. H., Clopton, P., Steg, P. G., Westheim, A., Knudsen, C. W., Perez, A., Kazanegra, R., Herrmann, H. C., McCullough, P. A., & Breathing Not Properly Multinational Study Investigators. (2002). Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. The New England Journal of Medicine, 347, 161–167.PubMedCrossRefGoogle Scholar
  6. 6.
    Januzzi, J. L., Jr., Camargo, C. A., Anwaruddin, S., Baggish, A. L., Chen, A. A., Krauser, D. G., Tung, R., Cameron, R., Nagurney, J. T., Chae, C. U., Lloyd-Jones, D. M., Brown, D. F., Foran-Melanson, S., Sluss, P. M., Lee-Lewandrowski, E., & Lewandrowski, K. B. (2005). The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study. The American Journal of Cardiology, 95, 948–954.PubMedCrossRefGoogle Scholar
  7. 7.
    Maisel, A. S., McCord, J., Nowak, R. M., Hollander, J. E., Wu, A. H., Duc, P., Omland, T., Storrow, A. B., Krishnaswamy, P., Abraham, W. T., Clopton, P., Steg, G., Aumont, M. C., Westheim, A., Knudsen, C. W., Perez, A., Kamin, R., Kazanegra, R., Herrmann, H. C., McCullough, P. A., & Breathing Not Properly Multinational Study Investigators. (2003). Bedside B-type natriuretic peptide in the emergency diagnosis of heart failure with reduced or preserved ejection fraction. Results from the Breathing Not Properly Multinational Study. J Am Coll Cardiol, 41, 2010–2017.PubMedCrossRefGoogle Scholar
  8. 8.
    O'Donoghue, M., Chen, A., Baggish, A. L., Anwaruddin, S., Krauser, D. G., Tung, R., & Januzzi, J. L. (2005). The effects of ejection fraction on N-terminal proBNP and BNP levels in patients with acute CHF: Analysis from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study. Journal of Cardiac Failure, 11, S9–S14.PubMedCrossRefGoogle Scholar
  9. 9.
    Steg, P. G., Joubin, L., McCord, J., Abraham, W. T., Hollander, J. E., Omland, T., Mentre, F., McCullough, P. A., & Maisel, A. S. (2005). B-type natriuretic peptide and echocardiographic determination of ejection fraction in the diagnosis of congestive heart failure in patients with acute dyspnea. Chest, 128, 21–29.PubMedCrossRefGoogle Scholar
  10. 10.
    Felker, G. M., Hasselblad, V., Hernandez, A. F., & O'Connor, C. M. (2009). Biomarker-guided therapy in chronic heart failure: A meta-analysis of randomized controlled trials. American Heart Journal, 158, 422–430.PubMedCrossRefGoogle Scholar
  11. 11.
    Januzzi, J. L., Jr., Rehman, S. U., Mohammed, A. A., Bhardwaj, A., Barajas, L., Barajas, J., Kim, H. N., Baggish, A. L., Weiner, R. B., Chen-Tournoux, A., Marshall, J. E., Moore, S. A., Carlson, W. D., Lewis, G. D., Shin, J., Sullivan, D., Parks, K., Wang, T. J., Gregory, S. A., Uthamalingam, S., & Semigran, M. J. (2011). Use of amino-terminal pro-B-type natriuretic peptide to guide outpatient therapy of patients with chronic left ventricular systolic dysfunction. J Am Coll Cardiol, 58, 1881–1889.PubMedCrossRefGoogle Scholar
  12. 12.
    Macheret, F., Boerrigter, G., McKie, P., Costello-Boerrigter, L., Lahr, B., Heublein, D., Sandberg, S., Ikeda, Y., Cataliotti, A., Bailey, K., Rodeheffer, R., & Burnett, J. C., Jr. (2011). Pro-B-type natriuretic peptide(1–108) circulates in the general community: Plasma determinants and detection of left ventricular dysfunction. Journal of the American College of Cardiology, 57, 1386–1395.PubMedCrossRefGoogle Scholar
  13. 13.
    Costello-Boerrigter, L. C., Boerrigter, G., Redfield, M. M., Rodeheffer, R. J., Urban, L. H., Mahoney, D. W., Jacobsen, S. J., Heublein, D. M., & Burnett, J. C., Jr. (2006). Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in the general community: Determinants and detection of left ventricular dysfunction. Journal of the American College of Cardiology, 47, 345–353.PubMedCrossRefGoogle Scholar
  14. 14.
    Redfield, M. M., Rodeheffer, R. J., Jacobsen, S. J., Mahoney, D. W., Bailey, K. R., & Burnett, J. C., Jr. (2002). Plasma brain natriuretic peptide concentration: Impact of age and gender. Journal of the American College of Cardiology, 40, 976–982.PubMedCrossRefGoogle Scholar
  15. 15.
    Yoshimura, M., Yasue, H., & Ogawa, H. (2001). Pathophysiological significance and clinical application of ANP and BNP in patients with heart failure. Canadian Journal of Physiology and Pharmacology, 79, 730–735.PubMedCrossRefGoogle Scholar
  16. 16.
    Morgenthaler, N. G., Struck, J., Thomas, B., & Bergmann, A. (2004). Immunoluminometric assay for the midregion of pro-atrial natriuretic peptide in human plasma. Clinical Chemistry, 50, 234–236.PubMedCrossRefGoogle Scholar
  17. 17.
    Moertl, D., Berger, R., Struck, J., Gleiss, A., Hammer, A., Morgenthaler, N. G., Bergmann, A., Huelsmann, M., & Pacher, R. (2009). Comparison of midregional pro-atrial and B-type natriuretic peptides in chronic heart failure: Influencing factors, detection of left ventricular systolic dysfunction, and prediction of death. Journal of the American College of Cardiology, 53, 1783–1790.PubMedCrossRefGoogle Scholar
  18. 18.
    von Haehling, S., Jankowska, E. A., Morgenthaler, N. G., Vassanelli, C., Zanolla, L., Rozentryt, P., Filippatos, G. S., Doehner, W., Koehler, F., Papassotiriou, J., Kremastinos, D. T., Banasiak, W., Struck, J., Ponikowski, P., Bergmann, A., & Anker, S. D. (2007). Comparison of midregional pro-atrial natriuretic peptide with N-terminal pro-B-type natriuretic peptide in predicting survival in patients with chronic heart failure. Journal of the American College of Cardiology, 50, 1973–1980.CrossRefGoogle Scholar
  19. 19.
    Weinberg, E. O., Shimpo, M., De Keulenaer, G. W., MacGillivray, C., Tominaga, S., Solomon, S. D., Rouleau, J. L., & Lee, R. T. (2002). Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Circulation, 106, 2961–2966.PubMedCrossRefGoogle Scholar
  20. 20.
    Sanada, S., Hakuno, D., Higgins, L. J., Schreiter, E. R., McKenzie, A. N., & Lee, R. T. (2007). IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system. Journal of Clinical Investigation, 117, 1538–1549.PubMedCrossRefGoogle Scholar
  21. 21.
    Pascual-Figal, D. A., Ordonez-Llanos, J., Tornel, P. L., Vazquez, R., Puig, T., Valdes, M., Cinca, J., de Luna, A. B., Bayes-Genis, A., & Investigators, M. (2009). Soluble ST2 for predicting sudden cardiac death in patients with chronic heart failure and left ventricular systolic dysfunction. Journal of the American College of Cardiology, 54, 2174–2179.PubMedCrossRefGoogle Scholar
  22. 22.
    Ky, B., French, B., McCloskey, K., Rame, J. E., McIntosh, E., Shahi, P., Dries, D. L., Tang, W. H., Wu, A. H., Fang, J. C., Boxer, R., Sweitzer, N. K., Levy, W. C., Goldberg, L. R., Jessup, M., & Cappola, T. P. (2011). High-sensitivity ST2 for prediction of adverse outcomes in chronic heart failure. Circulation. Heart Failure, 4, 180–187.PubMedCrossRefGoogle Scholar
  23. 23.
    Shah, R. V., Chen-Tournoux, A. A., Picard, M. H., van Kimmenade, R. R., & Januzzi, J. L. (2009). Serum levels of the interleukin-1 receptor family member ST2, cardiac structure and function, and long-term mortality in patients with acute dyspnea. Circulation. Heart Failure, 2, 311–319.PubMedCrossRefGoogle Scholar
  24. 24.
    Jungbauer, C. G., Riedlinger, J., Buchner, S., Birner, C., Resch, M., Lubnow, M., Debl, K., Buesing, M., Huedig, H., Riegger, G., & Luchner, A. (2011). High-sensitive troponin T in chronic heart failure correlates with severity of symptoms, left ventricular dysfunction and prognosis independently from N-terminal pro-B-type natriuretic peptide. Clinical Chemistry and Laboratory Medicine, 49, 1899–1906.PubMedCrossRefGoogle Scholar
  25. 25.
    Sato, Y., Fujiwara, H., & Takatsu, Y. (2012). Cardiac troponin and heart failure in the era of high-sensitivity assays. Journal of Cardiology, 60, 160–167.PubMedCrossRefGoogle Scholar
  26. 26.
    Schaap, F. G., van der Vusse, G. J., & Glatz, J. F. (1998). Fatty acid-binding proteins in the heart. Molecular and Cellular Biochemistry, 180, 43–51.PubMedCrossRefGoogle Scholar
  27. 27.
    Niizeki, T., Takeishi, Y., Arimoto, T., Takabatake, N., Nozaki, N., Hirono, O., Watanabe, T., Nitobe, J., Harada, M., Suzuki, S., Koyama, Y., Kitahara, T., Sasaki, T., & Kubota, I. (2007). Heart-type fatty acid-binding protein is more sensitive than troponin T to detect the ongoing myocardial damage in chronic heart failure patients. Journal of Cardiac Failure, 13, 120–127.PubMedCrossRefGoogle Scholar
  28. 28.
    Setsuta, K., Seino, Y., Ogawa, T., Arao, M., Miyatake, Y., & Takano, T. (2002). Use of cytosolic and myofibril markers in the detection of ongoing myocardial damage in patients with chronic heart failure. American Journal of Medicine, 113, 717–722.PubMedCrossRefGoogle Scholar
  29. 29.
    Arimoto, T., Takeishi, Y., Shiga, R., Fukui, A., Tachibana, H., Nozaki, N., Hirono, O., Nitobe, J., Miyamoto, T., Hoit, B. D., & Kubota, I. (2005). Prognostic value of elevated circulating heart-type fatty acid binding protein in patients with congestive heart failure. Journal of Cardiac Failure, 11, 56–60.PubMedCrossRefGoogle Scholar
  30. 30.
    Niessner, A., Hohensinner, P. J., Rychli, K., Neuhold, S., Zorn, G., Richter, B., Hulsmann, M., Berger, R., Mortl, D., Huber, K., Wojta, J., & Pacher, R. (2009). Prognostic value of apoptosis markers in advanced heart failure patients. European Heart Journal, 30, 789–796.PubMedCrossRefGoogle Scholar
  31. 31.
    Kinugawa, T., Kato, M., Yamamoto, K., Hisatome, I., & Nohara, R. (2012). Proinflammatory cytokine activation is linked to apoptotic mediator, soluble fas level in patients with chronic heart failure. International Heart Journal, 53, 182–186.PubMedCrossRefGoogle Scholar
  32. 32.
    McPherron, A. C., Lawler, A. M., & Lee, S. J. (1997). Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature, 387, 83–90.PubMedCrossRefGoogle Scholar
  33. 33.
    George, I., Bish, L. T., Kamalakkannan, G., Petrilli, C. M., Oz, M. C., Naka, Y., Sweeney, H. L., & Maybaum, S. (2010). Myostatin activation in patients with advanced heart failure and after mechanical unloading. European Journal of Heart Failure, 12, 444–453.PubMedCrossRefGoogle Scholar
  34. 34.
    Sharma, M., Kambadur, R., Matthews, K. G., Somers, W. G., Devlin, G. P., Conaglen, J. V., Fowke, P. J., & Bass, J. J. (1999). Myostatin, a transforming growth factor-beta superfamily member, is expressed in heart muscle and is upregulated in cardiomyocytes after infarct. Journal of Cellular Physiology, 180, 1–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Gruson, D., Ahn, S. A., Ketelslegers, J. M., & Rousseau, M. F. (2011). Increased plasma myostatin in heart failure. European Journal of Heart Failure, 13, 734–736.PubMedCrossRefGoogle Scholar
  36. 36.
    Thomas, C. V., Coker, M. L., Zellner, J. L., Handy, J. R., Crumbley, A. J., 3rd, & Spinale, F. G. (1998). Increased matrix metalloproteinase activity and selective upregulation in lv myocardium from patients with end-stage dilated cardiomyopathy. Circulation, 97, 1708–1715.PubMedCrossRefGoogle Scholar
  37. 37.
    Spinale, F. G., Coker, M. L., Heung, L. J., Bond, B. R., Gunasinghe, H. R., Etoh, T., Goldberg, A. T., Zellner, J. L., & Crumbley, A. J. (2000). A matrix metalloproteinase induction/activation system exists in the human left ventricular myocardium and is upregulated in heart failure. Circulation, 102, 1944–1949.PubMedCrossRefGoogle Scholar
  38. 38.
    Eckhouse, S. R., & Spinale, F. G. (2012). Changes in the myocardial interstitium and contribution to the progression of heart failure. Heart Failure Clinics, 8, 7–20.PubMedCrossRefGoogle Scholar
  39. 39.
    Spinale, F. G. (2007). Myocardial matrix remodeling and the matrix metalloproteinases: Influence on cardiac form and function. Physiological Reviews, 87, 1285–1342.PubMedCrossRefGoogle Scholar
  40. 40.
    Li, Y. Y., Feldman, A. M., Sun, Y., & McTiernan, C. F. (1998). Differential expression of tissue inhibitors of metalloproteinases in the failing human heart. Circulation, 98, 1728–1734.PubMedCrossRefGoogle Scholar
  41. 41.
    Cicoira, M., Rossi, A., Bonapace, S., Zanolla, L., Golia, G., Franceschini, L., Caruso, B., Marino, P. N., & Zardini, P. (2004). Independent and additional prognostic value of aminoterminal propeptide of type III procollagen circulating levels in patients with chronic heart failure. Journal of Cardiac Failure, 10, 403–411.PubMedCrossRefGoogle Scholar
  42. 42.
    Sundstrom, J., Evans, J. C., Benjamin, E. J., Levy, D., Larson, M. G., Sawyer, D. B., Siwik, D. A., Colucci, W. S., Wilson, P. W., & Vasan, R. S. (2004). Relations of plasma total TIMP-1 levels to cardiovascular risk factors and echocardiographic measures: The Framingham Heart Study. European Heart Journal, 25, 1509–1516.PubMedCrossRefGoogle Scholar
  43. 43.
    Bruggink, A. H., van Oosterhout, M. F., de Jonge, N., Ivangh, B., van Kuik, J., Voorbij, R. H., Cleutjens, J. P., Gmelig-Meyling, F. H., & de Weger, R. A. (2006). Reverse remodeling of the myocardial extracellular matrix after prolonged left ventricular assist device support follows a biphasic pattern. The Journal of Heart and Lung Transplantation, 25, 1091–1098.PubMedCrossRefGoogle Scholar
  44. 44.
    Liu, Y. H., D'Ambrosio, M., Liao, T. D., Peng, H., Rhaleb, N. E., Sharma, U., Andre, S., Gabius, H. J., & Carretero, O. A. (2009). N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin. American Journal of Physiology - Heart and Circulatory Physiology, 296, H404–H412.PubMedCrossRefGoogle Scholar
  45. 45.
    Sharma, U. C., Pokharel, S., van Brakel, T. J., van Berlo, J. H., Cleutjens, J. P., Schroen, B., Andre, S., Crijns, H. J., Gabius, H. J., Maessen, J., & Pinto, Y. M. (2004). Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Circulation, 110, 3121–3128.PubMedCrossRefGoogle Scholar
  46. 46.
    Lopez-Andres, N., Rossignol, P., Iraqi, W., Fay, R., Nuee, J., Ghio, S., Cleland, J. G., Zannad, F., & Lacolley, P. (2012). Association of galectin-3 and fibrosis markers with long-term cardiovascular outcomes in patients with heart failure, left ventricular dysfunction, and dyssynchrony: Insights from the CARE-HF (Cardiac Resynchronization in Heart Failure) trial. European Journal of Heart Failure, 14, 74–81.PubMedCrossRefGoogle Scholar
  47. 47.
    Lok, D. J., Lok, S. I., Bruggink-Andre de la Porte, P. W., Badings, E., Lipsic, E., van Wijngaarden, J., de Boer, R. A., van Veldhuisen, D. J., van der Meer, P. (2012). Galectin-3 is an independent marker for ventricular remodeling and mortality in patients with chronic heart failure. Clinical Research in Cardiology, 102, 103–110.Google Scholar
  48. 48.
    Ho, J. E., Liu, C., Lyass, A., Courchesne, P., Pencina, M. J., Vasan, R. S., Larson, M. G., & Levy, D. (2012). Galectin-3, a marker of cardiac fibrosis, predicts incident heart failure in the community. Journal of the American College of Cardiology, 60, 1249–1256.PubMedCrossRefGoogle Scholar
  49. 49.
    Levine, B., Kalman, J., Mayer, L., Fillit, H. M., & Packer, M. (1990). Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. The New England Journal of Medicine, 323, 236–241.PubMedCrossRefGoogle Scholar
  50. 50.
    Mann, D. L. (2002). Inflammatory mediators and the failing heart: Past, present, and the foreseeable future. Circulation Research, 91, 988–998.PubMedCrossRefGoogle Scholar
  51. 51.
    Ren, M. Y., & Sui, S. J. (2012). The role of TWEAK/Fn14 in cardiac remodeling. Molecular Biology Reports, 39, 9971–9977.PubMedCrossRefGoogle Scholar
  52. 52.
    Chorianopoulos, E., Rosenberg, M., Zugck, C., Wolf, J., Katus, H. A., & Frey, N. (2009). Decreased soluble TWEAK levels predict an adverse prognosis in patients with chronic stable heart failure. European Journal of Heart Failure, 11, 1050–1056.PubMedCrossRefGoogle Scholar
  53. 53.
    Richter, B., Rychli, K., Hohensinner, P. J., Berger, R., Mortl, D., Neuhold, S., Zorn, G., Huber, K., Maurer, G., Wojta, J., Pacher, R., Hulsmann, M., & Niessner, A. (2010). Differences in the predictive value of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in advanced ischemic and non-ischemic heart failure. Atherosclerosis, 213, 545–548.PubMedCrossRefGoogle Scholar
  54. 54.
    Ueland, T., Yndestad, A., Oie, E., Florholmen, G., Halvorsen, B., Froland, S. S., Simonsen, S., Christensen, G., Gullestad, L., & Aukrust, P. (2005). Dysregulated osteoprotegerin/RANK ligand/RANK axis in clinical and experimental heart failure. Circulation, 111, 2461–2468.PubMedCrossRefGoogle Scholar
  55. 55.
    Roysland, R., Masson, S., Omland, T., Milani, V., Bjerre, M., Flyvbjerg, A., Di Tano, G., Misuraca, G., Maggioni, A. P., Tognoni, G., Tavazzi, L., Latini, R., & Investigators, G.-H. (2010). Prognostic value of osteoprotegerin in chronic heart failure: The GISSI-HF trial. American Heart Journal, 160, 286–293.PubMedCrossRefGoogle Scholar
  56. 56.
    Bottazzi, B., Doni, A., Garlanda, C., & Mantovani, A. (2010). An integrated view of humoral innate immunity: Pentraxins as a paradigm. Annual Review of Immunology, 28, 157–183.PubMedCrossRefGoogle Scholar
  57. 57.
    Latini, R., Gullestad, L., Masson, S., Nymo, S. H., Ueland, T., Cuccovillo, I., Vardal, M., Bottazzi, B., Mantovani, A., Lucci, D., Masuda, N., Sudo, Y., Wikstrand, J., Tognoni, G., Aukrust, P., Tavazzi, L., et al. (2012). Pentraxin-3 in chronic heart failure: The CORONA and GISSI-HF trials. European Journal of Heart Failure, 14, 992–999.PubMedCrossRefGoogle Scholar
  58. 58.
    Suzuki, S., Takeishi, Y., Niizeki, T., Koyama, Y., Kitahara, T., Sasaki, T., Sagara, M., & Kubota, I. (2008). Pentraxin 3, a new marker for vascular inflammation, predicts adverse clinical outcomes in patients with heart failure. American Heart Journal, 155, 75–81.PubMedCrossRefGoogle Scholar
  59. 59.
    Tsutamoto, T., Wada, A., Maeda, K., Mabuchi, N., Hayashi, M., Tsutsui, T., Ohnishi, M., Fujii, M., Matsumoto, T., Yamamoto, T., Wang, X., Asai, S., Tsuji, T., Tanaka, H., Saito, Y., Kuwahara, K., Nakao, K., & Kinoshita, M. (2001). Relationship between plasma level of cardiotrophin-1 and left ventricular mass index in patients with dilated cardiomyopathy. Journal of the American College of Cardiology, 38, 1485–1490.PubMedCrossRefGoogle Scholar
  60. 60.
    Braunwald, E. (2008). Biomarkers in heart failure. The New England Journal of Medicine, 358, 2148–2159.PubMedCrossRefGoogle Scholar
  61. 61.
    Steinberg, S. F. (2013). Oxidative stress and sarcomeric proteins. Circulation Research, 112, 393–405.PubMedCrossRefGoogle Scholar
  62. 62.
    Vasilyev, N., Williams, T., Brennan, M. L., Unzek, S., Zhou, X., Heinecke, J. W., Spitz, D. R., Topol, E. J., Hazen, S. L., & Penn, M. S. (2005). Myeloperoxidase-generated oxidants modulate left ventricular remodeling but not infarct size after myocardial infarction. Circulation, 112, 2812–2820.PubMedCrossRefGoogle Scholar
  63. 63.
    Nicholls, S. J., & Hazen, S. L. (2005). Myeloperoxidase and cardiovascular disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 25, 1102–1111.PubMedCrossRefGoogle Scholar
  64. 64.
    Tang, W. H., Tong, W., Troughton, R. W., Martin, M. G., Shrestha, K., Borowski, A., Jasper, S., Hazen, S. L., & Klein, A. L. (2007). Prognostic value and echocardiographic determinants of plasma myeloperoxidase levels in chronic heart failure. Journal of the American College of Cardiology, 49, 2364–2370.PubMedCrossRefGoogle Scholar
  65. 65.
    Andreou, I., Tousoulis, D., Miliou, A., Tentolouris, C., Zisimos, K., Gounari, P., Siasos, G., Papageorgiou, N., Papadimitriou, C. A., Dimopoulos, M. A., & Stefanadis, C. (2010). Effects of rosuvastatin on myeloperoxidase levels in patients with chronic heart failure: A randomized placebo-controlled study. Atherosclerosis, 210, 194–198.PubMedCrossRefGoogle Scholar
  66. 66.
    Tsutamoto, T., Wada, A., Matsumoto, T., Maeda, K., Mabuchi, N., Hayashi, M., Tsutsui, T., Ohnishi, M., Sawaki, M., Fujii, M., Yamamoto, T., Horie, H., Sugimoto, Y., & Kinoshita, M. (2001). Relationship between tumor necrosis factor-alpha production and oxidative stress in the failing hearts of patients with dilated cardiomyopathy. Journal of the American College of Cardiology, 37, 2086–2092.PubMedCrossRefGoogle Scholar
  67. 67.
    Yamaji, M., Tsutamoto, T., Kawahara, C., Nishiyama, K., Yamamoto, T., Fujii, M., & Horie, M. (2009). Serum cortisol as a useful predictor of cardiac events in patients with chronic heart failure: The impact of oxidative stress. Circulation. Heart Failure, 2, 608–615.PubMedCrossRefGoogle Scholar
  68. 68.
    Tsutsui, T., Tsutamoto, T., Wada, A., Maeda, K., Mabuchi, N., Hayashi, M., Ohnishi, M., & Kinoshita, M. (2002). Plasma oxidized low-density lipoprotein as a prognostic predictor in patients with chronic congestive heart failure. Journal of the American College of Cardiology, 39, 957–962.PubMedCrossRefGoogle Scholar
  69. 69.
    Taegtmeyer, H. (2004). Cardiac metabolism as a target for the treatment of heart failure. Circulation, 110, 894–896.PubMedCrossRefGoogle Scholar
  70. 70.
    Neubauer, S. (2007). The failing heart—An engine out of fuel. The New England Journal of Medicine, 356, 1140–1151.PubMedCrossRefGoogle Scholar
  71. 71.
    Biolo, A., Shibata, R., Ouchi, N., Kihara, S., Sonoda, M., Walsh, K., & Sam, F. (2010). Determinants of adiponectin levels in patients with chronic systolic heart failure. The American Journal of Cardiology, 105, 1147–1152.PubMedCrossRefGoogle Scholar
  72. 72.
    Frankel, D. S., Vasan, R. S., D'Agostino, R. B., Sr., Benjamin, E. J., Levy, D., Wang, T. J., & Meigs, J. B. (2009). Resistin, adiponectin, and risk of heart failure the Framingham offspring study. Journal of the American College of Cardiology, 53, 754–762.PubMedCrossRefGoogle Scholar
  73. 73.
    Nanayakkara, G., Kariharan, T., Wang, L., Zhong, J., & Amin, R. (2012). The cardio-protective signaling and mechanisms of adiponectin. Am J Cardiovasc Dis., 2, 253–266.PubMedGoogle Scholar
  74. 74.
    Khan, R. S., Kato, T. S., Chokshi, A., Chew, M., Yu, S., Wu, C., Singh, P., Cheema, F. H., Takayama, H., Harris, C., Reyes-Soffer, G., Knoll, R., Milting, H., Naka, Y., Mancini, D., & Schulze, P. C. (2012). Adipose tissue inflammation and adiponectin resistance in patients with advanced heart failure: Correction after ventricular assist device implantation. Circulation. Heart Failure, 5, 340–348.PubMedCrossRefGoogle Scholar
  75. 75.
    Schulze, P. C., Biolo, A., Gopal, D., Shahzad, K., Balog, J., Fish, M., Siwik, D., & Colucci, W. S. (2011). Dynamics in insulin resistance and plasma levels of adipokines in patients with acute decompensated and chronic stable heart failure. Journal of Cardiac Failure, 17, 1004–1011.PubMedCrossRefGoogle Scholar
  76. 76.
    Hopkins, T. A., Ouchi, N., Shibata, R., & Walsh, K. (2007). Adiponectin actions in the cardiovascular system. Cardiovascular Research, 74, 11–18.PubMedCrossRefGoogle Scholar
  77. 77.
    Hotta, K., Funahashi, T., Arita, Y., Takahashi, M., Matsuda, M., Okamoto, Y., Iwahashi, H., Kuriyama, H., Ouchi, N., Maeda, K., Nishida, M., Kihara, S., Sakai, N., Nakajima, T., Hasegawa, K., Muraguchi, M., Ohmoto, Y., Nakamura, T., Yamashita, S., Hanafusa, T., & Matsuzawa, Y. (2000). Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arteriosclerosis, Thrombosis, and Vascular Biology, 20, 1595–1599.PubMedCrossRefGoogle Scholar
  78. 78.
    Iwashima, Y., Katsuya, T., Ishikawa, K., Ouchi, N., Ohishi, M., Sugimoto, K., Fu, Y., Motone, M., Yamamoto, K., Matsuo, A., Ohashi, K., Kihara, S., Funahashi, T., Rakugi, H., Matsuzawa, Y., & Ogihara, T. (2004). Hypoadiponectinemia is an independent risk factor for hypertension. Hypertension, 43, 1318–1323.PubMedCrossRefGoogle Scholar
  79. 79.
    Kumada, M., Kihara, S., Sumitsuji, S., Kawamoto, T., Matsumoto, S., Ouchi, N., Arita, Y., Okamoto, Y., Shimomura, I., Hiraoka, H., Nakamura, T., Funahashi, T., Matsuzawa, Y., & for the Osaka CAD Study Group. (2003). Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol., 23, 85–89.PubMedCrossRefGoogle Scholar
  80. 80.
    Kistorp, C., Faber, J., Galatius, S., Gustafsson, F., Frystyk, J., Flyvbjerg, A., & Hildebrandt, P. (2005). Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure. Circulation, 112, 1756–1762.PubMedCrossRefGoogle Scholar
  81. 81.
    Haugen, E., Furukawa, Y., Isic, A., & Fu, M. (2008). Increased adiponectin level in parallel with increased NT-pro BNP in patients with severe heart failure in the elderly: A hospital cohort study. International Journal of Cardiology, 125, 216–219.PubMedCrossRefGoogle Scholar
  82. 82.
    George, J., Patal, S., Wexler, D., Sharabi, Y., Peleg, E., Kamari, Y., Grossman, E., Sheps, D., Keren, G., & Roth, A. (2006). Circulating adiponectin concentrations in patients with congestive heart failure. Heart, 92, 1420–1424.PubMedCrossRefGoogle Scholar
  83. 83.
    Takano, H., Obata, J. E., Kodama, Y., Kitta, Y., Nakamura, T., Mende, A., Kawabata, K., Saito, Y., Fujioka, D., Kobayashi, T., Yano, T., Sano, K., & Kugiyama, K. (2009). Adiponectin is released from the heart in patients with heart failure. International Journal of Cardiology, 132, 221–226.PubMedCrossRefGoogle Scholar
  84. 84.
    Potocki, M., Ziller, R., & Mueller, C. (2012). Mid-regional pro-adrenomedullin in acute heart failure: A better biomarker or just another biomarker? Current Heart Failure Reports, 9, 244–251.PubMedCrossRefGoogle Scholar
  85. 85.
    Adlbrecht, C., Hulsmann, M., Strunk, G., Berger, R., Mortl, D., Struck, J., Morgenthaler, N. G., Bergmann, A., Jakowitsch, J., Maurer, G., Lang, I. M., & Pacher, R. (2009). Prognostic value of plasma midregional pro-adrenomedullin and C-terminal-pro-endothelin-1 in chronic heart failure outpatients. European Journal of Heart Failure, 11, 361–366.PubMedCrossRefGoogle Scholar
  86. 86.
    Neuhold, S., Huelsmann, M., Strunk, G., Stoiser, B., Struck, J., Morgenthaler, N. G., Bergmann, A., Moertl, D., Berger, R., & Pacher, R. (2008). Comparison of copeptin, B-type natriuretic peptide, and amino-terminal pro-B-type natriuretic peptide in patients with chronic heart failure: Prediction of death at different stages of the disease. Journal of the American College of Cardiology, 52, 266–272.PubMedCrossRefGoogle Scholar
  87. 87.
    Voors, A. A., von Haehling, S., Anker, S. D., Hillege, H. L., Struck, J., Hartmann, O., Bergmann, A., Squire, I., van Veldhuisen, D. J., Dickstein, K., & Investigators, O. (2009). C-terminal provasopressin (copeptin) is a strong prognostic marker in patients with heart failure after an acute myocardial infarction: Results from the OPTIMAAL study. European Heart Journal, 30, 1187–1194.PubMedCrossRefGoogle Scholar
  88. 88.
    Carubelli, V., Metra, M., Lombardi, C., Bettari, L., Bugatti, S., Lazzarini, V., & Dei, C. L. (2012). Renal dysfunction in acute heart failure: Epidemiology, mechanisms and assessment. Hear Fail Rev, 17, 271–282.CrossRefGoogle Scholar
  89. 89.
    Schmidt-Ott, K. M., Mori, K., Li, J. Y., Kalandadze, A., Cohen, D. J., Devarajan, P., & Barasch, J. (2007). Dual action of neutrophil gelatinase-associated lipocalin. Journal of the American Society of Nephrology, 18, 407–413.PubMedCrossRefGoogle Scholar
  90. 90.
    Maisel, A. S., Mueller, C., Fitzgerald, R., Brikhan, R., Hiestand, B. C., Iqbal, N., Clopton, P., & van Veldhuisen, D. J. (2011). Prognostic utility of plasma neutrophil gelatinase-associated lipocalin in patients with acute heart failure: The NGAL EvaLuation Along with B-type NaTriuretic Peptide in acutely decompensated heart failure (GALLANT) trial. European Journal of Heart Failure, 13, 846–851.PubMedCrossRefGoogle Scholar
  91. 91.
    Shrestha, K., Shao, Z., Singh, D., Dupont, M., & Tang, W. H. (2012). Relation of systemic and urinary neutrophil gelatinase-associated lipocalin levels to different aspects of impaired renal function in patients with acute decompensated heart failure. The American Journal of Cardiology, 110, 1329–1335.PubMedCrossRefGoogle Scholar
  92. 92.
    Shrestha, K., Borowski, A. G., Troughton, R. W., Klein, A. L., & Tang, W. H. (2012). Association between systemic neutrophil gelatinase-associated lipocalin and anemia, relative hypochromia, and inflammation in chronic systolic heart failure. Congestive Heart Failure, 18, 239–244.PubMedCrossRefGoogle Scholar
  93. 93.
    Chen, H. H. (2011). Beta-trace protein versus cystatin C: Which is a better surrogate marker of renal function versus prognostic indicator in cardiovascular diseases? Journal of the American College of Cardiology, 57, 859–860.PubMedCrossRefGoogle Scholar
  94. 94.
    Damman, K., Van Veldhuisen, D. J., Navis, G., Vaidya, V. S., Smilde, T. D., Westenbrink, B. D., Bonventre, J. V., Voors, A. A., & Hillege, H. L. (2010). Tubular damage in chronic systolic heart failure is associated with reduced survival independent of glomerular filtration rate. Heart, 96, 1297–1302.PubMedCrossRefGoogle Scholar
  95. 95.
    Wang, T. J., Wollert, K. C., Larson, M. G., Coglianese, E., McCabe, E. L., Cheng, S., Ho, J. E., Fradley, M. G., Ghorbani, A., Xanthakis, V., Kempf, T., Benjamin, E. J., Levy, D., Vasan, R. S., & Januzzi, J. L. (2012). Prognostic utility of novel biomarkers of cardiovascular stress: The Framingham Heart Study. Circulation, 126, 1596–1604.PubMedCrossRefGoogle Scholar
  96. 96.
    Lok, S. I., Winkens, B., Goldschmeding, R., van Geffen, A. J., Nous, F. M., van Kuik, J., van der Weide, P., Klopping, C., Kirkels, J. H., Lahpor, J. R., Doevendans, P. A., de Jonge, N., & de Weger, R. A. (2012). Circulating growth differentiation factor-15 correlates with myocardial fibrosis in patients with non-ischaemic dilated cardiomyopathy and decreases rapidly after left ventricular assist device support. European Journal of Heart Failure, 14, 1249–1256.PubMedCrossRefGoogle Scholar
  97. 97.
    Kawabata, D., Tanaka, M., Fujii, T., Umehara, H., Fujita, Y., Yoshifuji, H., Mimori, T., & Ozaki, S. (2004). Ameliorative effects of follistatin-related protein/TSC-36/FSTL1 on joint inflammation in a mouse model of arthritis. Arthritis and Rheumatism, 50, 660–668.PubMedCrossRefGoogle Scholar
  98. 98.
    Le Luduec, J. B., Condamine, T., Louvet, C., Thebault, P., Heslan, J. M., Heslan, M., Chiffoleau, E., & Cuturi, M. C. (2008). An immunomodulatory role for follistatin-like 1 in heart allograft transplantation. American Journal of Transplantation, 8, 2297–2306.PubMedCrossRefGoogle Scholar
  99. 99.
    Miyamae, T., Marinov, A. D., Sowders, D., Wilson, D. C., Devlin, J., Boudreau, R., Robbins, P., & Hirsch, R. (2006). Follistatin-like protein-1 is a novel proinflammatory molecule. Journal of Immunology, 177, 4758–4762.Google Scholar
  100. 100.
    El-Armouche, A., Ouchi, N., Tanaka, K., Doros, G., Wittkopper, K., Schulze, T., Eschenhagen, T., Walsh, K., & Sam, F. (2011). Follistatin-like 1 in chronic systolic heart failure: A marker of left ventricular remodeling. Circulation. Heart Failure, 4, 621–627.PubMedCrossRefGoogle Scholar
  101. 101.
    Lara-Pezzi, E., Felkin, L. E., Birks, E. J., Sarathchandra, P., Panse, K. D., George, R., Hall, J. L., Yacoub, M. H., Rosenthal, N., & Barton, P. J. (2008). Expression of follistatin-related genes is altered in heart failure. Endocrinology, 149, 5822–5827.PubMedCrossRefGoogle Scholar
  102. 102.
    de Boer, R. A., Lok, D. J., Jaarsma, T., van der Meer, P., Voors, A. A., Hillege, H. L., & van Veldhuisen, D. J. (2011). Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction. Annals of Medicine, 43, 60–68.PubMedCrossRefGoogle Scholar
  103. 103.
    Grewal, J., McKelvie, R., Lonn, E., Tait, P., Carlsson, J., Gianni, M., Jarnert, C., & Persson, H. (2008). BNP and NT-proBNP predict echocardiographic severity of diastolic dysfunction. European Journal of Heart Failure, 10, 252–259.PubMedCrossRefGoogle Scholar
  104. 104.
    Grewal, J., McKelvie, R. S., Persson, H., Tait, P., Carlsson, J., Swedberg, K., Ostergren, J., & Lonn, E. (2008). Usefulness of N-terminal pro-brain natriuretic peptide and brain natriuretic peptide to predict cardiovascular outcomes in patients with heart failure and preserved left ventricular ejection fraction. The American Journal of Cardiology, 102, 733–737.PubMedCrossRefGoogle Scholar
  105. 105.
    Manzano-Fernandez, S., Mueller, T., Pascual-Figal, D., Truong, Q. A., & Januzzi, J. L. (2011). Usefulness of soluble concentrations of interleukin family member ST2 as predictor of mortality in patients with acutely decompensated heart failure relative to left ventricular ejection fraction. The American Journal of Cardiology, 107, 259–267.PubMedCrossRefGoogle Scholar
  106. 106.
    Matsubara, J., Sugiyama, S., Nozaki, T., Sugamura, K., Konishi, M., Ohba, K., Matsuzawa, Y., Akiyama, E., Yamamoto, E., Sakamoto, K., Nagayoshi, Y., Kaikita, K., Sumida, H., Kim-Mitsuyama, S., & Ogawa, H. (2011). Pentraxin 3 is a new inflammatory marker correlated with left ventricular diastolic dysfunction and heart failure with normal ejection fraction. Journal of the American College of Cardiology, 57, 861–869.PubMedCrossRefGoogle Scholar
  107. 107.
    McKelvie, R. S., Komajda, M., McMurray, J., Zile, M., Ptaszynska, A., Donovan, M., Carson, P., Massie, B. M., & Investigators, I. P. (2010). Baseline plasma NT-proBNP and clinical characteristics: Results from the irbesartan in heart failure with preserved ejection fraction trial. Journal of Cardiac Failure, 16, 128–134.PubMedCrossRefGoogle Scholar
  108. 108.
    Chu, J. W., Jones, G. T., Tarr, G. P., Phillips, L. V., Wilkins, G. T., van Rij, A. M., Williams, M. J. (2012). Plasma active matrix metalloproteinase 9 and indices of diastolic function in patients with preserved systolic function. International Journal of Cardiology. doi: 10.1016/j.ijcard.2012.03.147.
  109. 109.
    Martos, R., Baugh, J., Ledwidge, M., O'Loughlin, C., Murphy, N. F., Conlon, C., Patle, A., Donnelly, S. C., & McDonald, K. (2009). Diagnosis of heart failure with preserved ejection fraction: Improved accuracy with the use of markers of collagen turnover. European Journal of Heart Failure, 11, 191–197.PubMedCrossRefGoogle Scholar
  110. 110.
    Roysland, R., Bonaca, M. P., Omland, T., Sabatine, M., Murphy, S. A., Scirica, B. M., Bjerre, M., Flyvbjerg, A., Braunwald, E., & Morrow, D. A. (2012). Osteoprotegerin and cardiovascular mortality in patients with non-ST elevation acute coronary syndromes. Heart, 98, 786–791.PubMedCrossRefGoogle Scholar
  111. 111.
    Ueland, T., Dahl, C. P., Kjekshus, J., Hulthe, J., Bohm, M., Mach, F., Goudev, A., Lindberg, M., Wikstrand, J., Aukrust, P., & Gullestad, L. (2011). Osteoprotegerin predicts progression of chronic heart failure: Results from CORONA. Circulation. Heart Failure, 4, 145–152.PubMedCrossRefGoogle Scholar
  112. 112.
    Palladini, G., Barassi, A., Perlini, S., Milani, P., Foli, A., Russo, P., Albertini, R., Obici, L., Lavatelli, F., Sarais, G., Casarini, S., Moratti, R., Melzi d'Eril, G. V., & Merlini, G. (2011). Midregional proadrenomedullin (MR-proADM) is a powerful predictor of early death in AL amyloidosis. Amyloid., 18, 216–221.PubMedCrossRefGoogle Scholar
  113. 113.
    Carlsson, A. C., Larsson, A., Helmersson-Karlqvist, J., Lind, L., Ingelsson, E., Larsson, T. E., Sundstrom, J., Arnlov, J. (2012). Urinary kidney injury molecule 1 and incidence of heart failure in elderly men. European Journal of Heart Failure, 15, 441–446.Google Scholar
  114. 114.
    Ky, B., French, B., Levy, W. C., Sweitzer, N. K., Fang, J. C., Wu, A. H., Goldberg, L. R., Jessup, M., & Cappola, T. P. (2012). Multiple biomarkers for risk prediction in chronic heart failure. Circulation. Heart Failure, 5, 183–190.PubMedCrossRefGoogle Scholar
  115. 115.
    Tanaka, K., Essick, E. E., Doros, G., Tanriverdi, K., Connors, L. H., Seldin, D. C., Sam, F. (2013). Circulating matrix metalloproteinases and tissue inhibitors of metalloproteinases in cardiac amyloidosis. Journal of the American Heart Association, 2(2), e005868. doi: 10.1161/JAHA.112.005868.
  116. 116.
    Amir, O., Rogowski, O., David, M., Lahat, N., Wolff, R., & Lewis, B. S. (2010). Circulating interleukin-10: Association with higher mortality in systolic heart failure patients with elevated tumor necrosis factor-alpha. The Israel Medical Association Journal, 12, 158–162.PubMedGoogle Scholar
  117. 117.
    Miettinen, K. H., Lassus, J., Harjola, V. P., Siirila-Waris, K., Melin, J., Punnonen, K. R., Nieminen, M. S., Laakso, M., & Peuhkurinen, K. J. (2008). Prognostic role of pro- and anti-inflammatory cytokines and their polymorphisms in acute decompensated heart failure. European Journal of Heart Failure, 10, 396–403.PubMedCrossRefGoogle Scholar
  118. 118.
    Savic-Radojevic, A., Radovanovic, S., Pekmezovic, T., Pljesa-Ercegovac, M., Simic, D., Djukic, T., Matic, M., Simic, T. (2013). The role of serum VCAM-1 and TNF-alpha as predictors of mortality and morbidity in patients with chronic heart failure. Journal of Clinical Laboratory Analysis, 27, 105–112.Google Scholar
  119. 119.
    De Gennaro, L., Brunetti, N. D., Cuculo, A., Pellegrino, P. L., & Di Biase, M. (2008). Systemic inflammation in nonischemic dilated cardiomyopathy. Hear Vessel, 23, 445–450.CrossRefGoogle Scholar
  120. 120.
    Matsumoto, M., Tsujino, T., Lee-Kawabata, M., Naito, Y., Sakoda, T., Ohyanagi, M., & Masuyama, T. (2010). Serum interleukin-6 and C-reactive protein are markedly elevated in acute decompensated heart failure patients with left ventricular systolic dysfunction. Cytokine, 49, 264–268.PubMedCrossRefGoogle Scholar
  121. 121.
    Kosar, F., Aksoy, Y., Ozguntekin, G., Ozerol, I., & Varol, E. (2006). Relationship between cytokines and tumour markers in patients with chronic heart failure. European Journal of Heart Failure, 8, 270–274.PubMedCrossRefGoogle Scholar
  122. 122.
    Wykretowicz, A., Furmaniuk, J., Smielecki, J., Deskur-Smielecka, E., Szczepanik, A., Banaszak, A., & Wysocki, H. (2004). The oxygen stress index and levels of circulating interleukin-10 and interleukin-6 in patients with chronic heart failure. International Journal of Cardiology, 94, 283–287.PubMedCrossRefGoogle Scholar
  123. 123.
    Eslick, G. D., Thampan, B. V., Nalos, M., McLean, A. S., & Sluyter, R. (2009). Circulating interleukin-18 concentrations and a loss-of-function P2X7 polymorphism in heart failure. International Journal of Cardiology, 137, 81–83.PubMedCrossRefGoogle Scholar
  124. 124.
    Naito, Y., Tsujino, T., Fujioka, Y., Ohyanagi, M., Okamura, H., & Iwasaki, T. (2002). Increased circulating interleukin-18 in patients with congestive heart failure. Heart, 88, 296–297.PubMedCrossRefGoogle Scholar
  125. 125.
    Yamaoka-Tojo, M., Tojo, T., Inomata, T., Machida, Y., Osada, K., & Izumi, T. (2002). Circulating levels of interleukin 18 reflect etiologies of heart failure: Th1/Th2 cytokine imbalance exaggerates the pathophysiology of advanced heart failure. Journal of Cardiac Failure, 8, 21–27.PubMedCrossRefGoogle Scholar
  126. 126.
    Osmancik, P., Teringova, E., Tousek, P., Paulu, P., & Widimsky, P. (2013). Prognostic value of TNF-related apoptosis inducing ligand (TRAIL) in acute coronary syndrome patients. PLoS One, 8, e53860.PubMedCrossRefGoogle Scholar
  127. 127.
    Francis, G. S., Benedict, C., Johnstone, D. E., Kirlin, P. C., Nicklas, J., Liang, C. S., Kubo, S. H., Rudin-Toretsky, E., & Yusuf, S. (1990). Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD). Circulation, 82, 1724–1729.PubMedCrossRefGoogle Scholar
  128. 128.
    Latini, R., Masson, S., Anand, I., Salio, M., Hester, A., Judd, D., Barlera, S., Maggioni, A. P., Tognoni, G., Cohn, J. N., & Val-He, F. T. I. (2004). The comparative prognostic value of plasma neurohormones at baseline in patients with heart failure enrolled in Val-HeFT. European Heart Journal, 25, 292–299.PubMedCrossRefGoogle Scholar
  129. 129.
    Vergaro, G., Emdin, M., Iervasi, A., Zyw, L., Gabutti, A., Poletti, R., Mammini, C., Giannoni, A., Fontana, M., & Passino, C. (2011). Prognostic value of plasma renin activity in heart failure. The American Journal of Cardiology, 108, 246–251.PubMedCrossRefGoogle Scholar
  130. 130.
    Vantrimpont, P., Rouleau, J. L., Ciampi, A., Harel, F., de Champlain, J., Bichet, D., Moye, L. A., & Pfeffer, M. (1998). Two-year time course and significance of neurohumoral activation in the Survival and Ventricular Enlargement (SAVE) Study. European Heart Journal, 19, 1552–1563.PubMedCrossRefGoogle Scholar
  131. 131.
    Cicoira, M., Zanolla, L., Franceschini, L., Rossi, A., Golia, G., Zeni, P., Caruso, B., & Zardini, P. (2002). Relation of aldosterone “escape” despite angiotensin-converting enzyme inhibitor administration to impaired exercise capacity in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. The American Journal of Cardiology, 89, 403–407.PubMedCrossRefGoogle Scholar
  132. 132.
    Roig, E., Perez-Villa, F., Morales, M., Jimenez, W., Orus, J., Heras, M., & Sanz, G. (2000). Clinical implications of increased plasma angiotensin ii despite ace inhibitor therapy in patients with congestive heart failure. European Heart Journal, 21, 53–57.PubMedCrossRefGoogle Scholar
  133. 133.
    Goldsmith, S. R., Francis, G. S., Cowley, A. W., Jr., Levine, T. B., & Cohn, J. N. (1983). Increased plasma arginine vasopressin levels in patients with congestive heart failure. Journal of the American College of Cardiology, 1, 1385–1390.PubMedCrossRefGoogle Scholar
  134. 134.
    Szatalowicz, V. L., Arnold, P. E., Chaimovitz, C., Bichet, D., Berl, T., & Schrier, R. W. (1981). Radioimmunoassay of plasma arginine vasopressin in hyponatremic patients with congestive heart failure. The New England Journal of Medicine, 305, 263–266.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Cardiovascular Section and Evans Department of MedicineBoston University School of MedicineBostonUSA
  2. 2.Whitaker Cardiovascular InstituteBoston University School of MedicineBostonUSA

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