Abstract
Degenerative mitral valve disease is the most prevalent heart disease in dogs. Research on biomarkers of heart diseases has increased recently owing to their value in providing complementary information to gold standard diagnostic methods and enhancing the understanding of pathophysiology. Novel biomarkers, such as Galectin-3 (Gal-3), soluble interleukin-1 receptor-like 1 protein (sST2), and growth differentiation factor 15 (GDF-15), have demonstrated prognostic value in human medicine but are poorly studied in veterinary medicine. The purpose of this study was to determine the serum concentrations of these novel inflammatory biomarkers, along with traditional biomarkers, in dogs at different stages of degenerative mitral valve disease. Thirty-eight dogs were included: 14 in stage A, 10 in stage B2, and 14 in stage C. Serum concentrations of five biomarkers (Gal-3, sST2, GDF-15, fibrinogen, and C-reactive protein), echocardiography, thoracic radiography, clinical chemistry, and blood cell counts were assessed for each dog. Differences in biomarker concentrations between groups were analyzed. Fibrinogen and C-reactive protein concentrations were higher in group C than in group A. Galectin-3 concentrations were higher in group B2 compared to those in group C. GDF 15 concentrations were higher in group B2 than in group A. No significant differences were found between groups B2 and C. sST2 concentrations did not differ between the groups. In conclusion, the novel inflammatory biomarker GDF-15 was measurable in dogs and was elevated in stage B2, similar to Gal-3, suggesting that inflammation and fibrosis begin with cardiac remodeling before clinical signs appear. Classical biomarkers showed the expected behavior. Further studies are needed to determine whether treatment affects the behavior of novel biomarkers.
References
Acierno, M. J., Brown, S., Coleman, A. E., Jepson, R. E., Papich, M., Stepien, R. L., & Syme, H. M. (2018). ACVIM consensus statement: Guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats. Journal of Veterinary Internal Medicine, 32(6), 1803-1822. http://doi.org/10.1111/jvim.15331. PMid:30353952.
Ames, M. K., Atkins, C. E., Eriksson, A., & Hess, A. M. (2017). Aldosterone breakthrough in dogs with naturally occurring myxomatous mitral valve disease. Journal of Veterinary Cardiology, 19(3), 218-227. http://doi.org/10.1016/j.jvc.2017.03.001. PMid:28576479.
Arcuri, G., Valente, C., Romito, G., Bonsembiante, F., Mazzoldi, C., Contiero, B., Poser, H., & Guglielmini, C. (2024). Evaluation of galectin-3 in dogs with atrial fibrillation. Animals, 14(17), 2547. http://doi.org/10.3390/ani14172547. PMid:39272333.
Atkins, C., Bonagura, J., Ettinger, S., Fox, P., Gordon, S., Häggström, J., Hamlin, R., Keene, B., Luis-Fuentes, V., & Stepien, R. (2009). Guidelines for the diagnosis and treatment of canine chronic valvular heart disease. Journal of Veterinary Internal Medicine, 23(6), 1142-1150. http://doi.org/10.1111/j.1939-1676.2009.0392.x. PMid:19780929.
Ayça, B., Akın, F., Çelik, Ö., Şahin, İ., Yıldız, S. S., Avcı, I. I., Gülşen, K., Okuyan, E., & Dinçkal, M. H. (2015). Neutrophil to lymphocyte ratio is related to stent thrombosis and high mortality in patients with acute myocardial infarction. Angiology, 66(6), 545-552. http://doi.org/10.1177/0003319714542997. PMid:25024461.
Bayes-Genis, A., De Antonio, M., Vila, J., Peñafiel, J., Galán, A., Barallat, J., Zamora, E., Urrutia, A., & Lupón, J. (2014). Head-to-head comparison of 2 myocardial fibrosis biomarkers for long-term heart failure risk stratification: ST2 versus galectin-3. Journal of the American College of Cardiology, 63(2), 158-166. http://doi.org/10.1016/j.jacc.2013.07.087. PMid:24076531.
Boon, J. A. (2011). Veterinary echocardiography (2nd ed.). Wiley-Blackwell. Borgarelli, M., & Häggström, J. (2010). Canine degenerative myxomatous mitral valve disease: Natural history, clinical presentation and therapy. The Veterinary Clinics of North America. Small Animal Practice, 40(4), 651-663. http://doi.org/10.1016/j.cvsm.2010.03.008. PMid:20610017.
Borgarelli, M., Savarino, P., Crosara, S., Santilli, R. A., Chiavegato, D., Poggi, M., Bellino, C., La Rosa, G., Zanatta, R., Haggstrom, J., & Tarducci, A. (2008). Survival characteristics and prognostic variables of dogs with mitral regurgitation attributable to myxomatous valve disease. Journal of Veterinary Internal Medicine, 22(1), 120-128. http://doi.org/10.1111/j.1939-1676.2007.0008.x. PMid:18289298.
Buchanan, J. W., & Bücheler, J. (1995). Vertebral scale system to measure heart size in radiographs. Journal of the American Veterinary Medical Association, 206(2), 194-199. http://doi.org/10.2460/javma.1995.206.02.194. PMid:7751220.
Buchanan, W. J. (1977). Chronic mitral valve disease in the dog. Veterinary Medicine, Small Animal Clinician, 60(12), 75-95.
Cornell, C. C., Kittleson, M. D., Della Torre, P., Häggström, J., Lombard, C. W., Pedersen, H. D., Vollmar, A., & Wey, A. (2004). Allometric scaling of M‐mode cardiac measurements in normal adult dogs. Journal of Veterinary Internal Medicine, 18(3), 311-321. http://doi.org/10.1892/0891-6640(2004)18<311:ASOMCM>2.0.CO;2. PMid:15188817.
Cunningham, S. M., Rush, J. E., & Freeman, L. M. (2012). Systemic inflammation and endothelial dysfunction in dogs with congestive heart failure. Journal of Veterinary Internal Medicine, 26(3), 547-557. http://doi.org/10.1111/j.1939-1676.2012.00923.x. PMid:22489997.
de Boer, R. A., van Veldhuisen, D. J., Gansevoort, R. T., Muller Kobold, A. C., van Gilst, W. H., Hillege, H. L., Bakker, S. J. L., & van der Harst, P. (2012). The fibrosis marker galectin-3 and outcome in the general population. Journal of Internal Medicine, 272(1), 55-64. http://doi.org/10.1111/j.1365-2796.2011.02476.x. PMid:22026577.
Domanjko Petrič, A., Lukman, T., Verk, B., & Nemec Svete, A. (2018). Systemic inflammation in dogs with advanced-stage heart failure. Acta Veterinaria Scandinavica, 60(1), 20. http://doi.org/10.1186/s13028-018-0372-x. PMid:29573742.
Du, W., Piek, A., Schouten, E. M., van de Kolk, C. W. A., Mueller, C., Mebazaa, A., Voors, A. A., de Boer, R. A., & Sillje, H. H. W. (2018). Plasma levels of heart failure biomarkers are primarily a reflection of extracardiac production. Theranostics, 8(15), 4155-4169. http://doi.org/10.7150/thno.26055. PMid:30128044.
Eckersall, P. D., & Bell, R. (2010). Acute phase proteins: Biomarkers of infection and inflammation in veterinary medicine. Veterinary Journal (London, England), 185(1), 23-27. http://doi.org/10.1016/j.tvjl.2010.04.009. PMid:20621712.
Elster, S. K., Braunwald, E., & Wood, H. F. (1956). A study of C-reactive protein in the serum of patients with congestive heart failure. American Heart Journal, 51(4), 533-541. http://doi.org/10.1016/0002-8703(56)90099-0. PMid:13302128.
Emdin, M., Aimo, A., Vergaro, G., Bayes-Genis, A., Lupón, J., Latini, R., Meessen, J., Anand, I. S., Cohn, J. N., Gravning, J., Gullestad, L., Broch, K., Ueland, T., Nymo, S. H., Brunner-La Rocca, H. P., de Boer, R. A., Gaggin, H. K., Ripoli, A., Passino, C., & Januzzi Junior, J. L. (2018). sST2 predicts outcome in chronic heart failure beyond NT-proBNP and high-sensitivity troponin T. Journal of the American College of Cardiology, 72(19), 2309-2320. http://doi.org/10.1016/j.jacc.2018.08.2165. PMid:30384887.
Falk, T., Jonsson, L., Olsen, L. H., & Pedersen, H. D. (2006). Arteriosclerotic changes in the myocardium, lung, and kidney in dogs with chronic congestive heart failure and myxomatous mitral valve disease. Cardiovascular Pathology, 15(4), 185-193. http://doi.org/10.1016/j.carpath.2006.04.003. PMid:16844549.
Falk, T., Jönsson, L., Olsen, L. H., Tarnow, I., & Pedersen, H. D. (2010). Associations between cardiac pathology and clinical, echocardiographic and electrocardiographic findings in dogs with chronic congestive heart failure. Veterinary Journal (London, England: 1997), 185(1), 68-74. http://doi.org/10.1016/j.tvjl.2010.04.016. PMid:20494597.
Fonfara, S., Hetzel, U., Tew, S. R., Cripps, P., Dukes-McEwan, J., & Clegg, P. D. (2013). Expression of matrix metalloproteinases, their inhibitors, and lysyl oxidase in myocardial samples from dogs with end-stage systemic and cardiac diseases. American Journal of Veterinary Research, 74(2), 216-223. http://doi.org/10.2460/ajvr.74.2.216. PMid:23363345.
Frank, D., Kuhn, C., Brors, B., Hanselmann, C., Lüdde, M., Katus, H. A., & Frey, N. (2008). Gene expression pattern in biomechanically stretched cardiomyocytes: Evidence for a stretch-specific gene program. Hypertension, 51(2), 309-318. http://doi.org/10.1161/HYPERTENSIONAHA.107.098046. PMid:18158353.
Gandhi, P. U., Motiwala, S. R., Belcher, A. M., Gaggin, H. K., Weiner, R. B., Baggish, A. L., Fiuzat, M., Brunner-La Rocca, H.-P., & Januzzi Junior, J. L. (2015). Galectin-3 and mineralocorticoid receptor antagonist use in patients with chronic heart failure due to left ventricular systolic dysfunction. American Heart Journal, 169(3), 404-411.e3. http://doi.org/10.1016/j.ahj.2014.12.012. PMid:25728731.
Häggström, J., Boswood, A., O’Grady, M., Jöns, O., Smith, S., Swift, S., Borgarelli, M., Gavaghan, B., Kresken, J.-G., Patteson, M., Ablad, B., Bussadori, C. M., Glaus, T., Kovacević, A., Rapp, M., Santilli, R. A., Tidholm, A., Eriksson, A., Belanger, M. C., Deinert, M., Little, C. J. L., Kvart, C., French, A., Rønn-Landbo, M., Wess, G., Eggertsdottir, A. V., O’Sullivan, M. L., Schneider, M., Lombard, C. W., Dukes-McEwan, J., Willis, R., Louvet, A., & DiFruscia, R. (2008). Effect of pimobendan or benazepril hydrochloride on survival times in dogs with congestive heart failure caused by naturally occurring myxomatous mitral valve disease: The QUEST study. Journal of Veterinary Internal Medicine, 22(5), 1124-1135. http://doi.org/10.1111/j.1939-1676.2008.0150.x. PMid:18638016. Henderson, N. C., & Sethi, T. (2009). The regulation of inflammation by galectin-3. Immunological Reviews, 230(1), 160-171. http://doi.org/10.1111/j.1600-065X.2009.00794.x. PMid:19594635.
Hirschfield, G. M., & Pepys, M. B. (2003). C-reactive protein and cardiovascular disease: New insights from an old molecule. QJM, 96(11), 793-807. http://doi.org/10.1093/qjmed/hcg134. PMid:14566035.
Hurter, K., Spreng, D., Rytz, U., Schawalder, P., Ott-Knüsel, F., & Schmökel, H. (2005). Measurements of C-reactive protein in serum and lactate dehydrogenase in serum and synovial fluid of patients with osteoarthritis. Veterinary Journal (London, England : 1997), 169(2), 281-285. http://doi.org/10.1016/j.tvjl.2004.01.027. PMid:15727922.
Ibarrola, J., Garaikoetxea, M., Garcia-Peña, A., Matilla, L., Jover, E., Bonnard, B., Cuesta, M., Fernández-Celis, A., Jaisser, F., & López-Andrés, N. (2020). Beneficial effects of mineralocorticoid receptor antagonism on myocardial fibrosis in an experimental model of the myxomatous degeneration of the mitral valve. International Journal of Molecular Sciences, 21(15), 5372. http://doi.org/10.3390/ijms21155372. PMid:32731636.
Keene, B. W., Atkins, C. E., Bonagura, J. D., Fox, P. R., Häggström, J., Luis Fuentes, V., Oyama, M. A., Rush, J. E., Stepien, R., & Uechi, M. (2019). ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs. Journal of Veterinary Internal Medicine, 33(3), 1127-1140. http://doi.org/10.1111/jvim.15488. PMid:30974015.
Kim, Y.-M., Kim, S.-W., & Kim, J.-H. (2023). Galectin-3 is able to differentiate dogs with myxomatous mitral valve disease from healthy control dogs. American Journal of Veterinary Research, 84(9), 1-8. http://doi.org/10.2460/ajvr.23.03.0063.
Kjelgaard-Hansen, M., & Jacobsen, S. (2011). Assay validation and diagnostic applications of major acute-phase protein testing in companion animals. Clinics in Laboratory Medicine, 31(1), 51-70. http://doi.org/10.1016/j.cll.2010.10.002. PMid:21295722.
Klein, S., Nolte, I., Granados-Soler, J. L., Lietz, P., Sehn, M., Raue, J. F., Rohn, K., Packeiser, E.-M., & Bach, J.-P. (2022). Evaluation of new and old biomarkers in dogs with degenerative mitral valve disease. BMC Veterinary Research, 18(1), 256. http://doi.org/10.1186/s12917-022-03343-z. PMid:35780161.
Kosum, P., Siranart, N., Mattanapojanat, N., Phutinart, S., Kongruttanachok, N., Sinphurmsukskul, S., Siwamogsatham, S., Puwanant, S., & Ariyachaipanich, A. (2024). GDF-15: A novel biomarker of heart failure predicts short-term and long-term heart-failure rehospitalization and short-term mortality in patients with acute heart failure syndrome. BMC Cardiovascular Disorders, 24(1), 151. http://doi.org/10.1186/s12872-024-03802-5. PMid:38475710.
Kvart, C., & Häggström, J. (2002). Cardiac Auscultation and Phonocardiography in Dogs, Horses and Cats (Vol. 1). Clarence Kvart. Lax, A., Sanchez-Mas, J., Asensio-Lopez, M. C., Fernandez-Del Palacio, M. J., Caballero, L., Garrido, I. P., Pastor-Perez, F. J., Januzzi, J. L., & Pascual-Figal, D. A. (2015). Mineralocorticoid receptor antagonists modulate galectin-3 and interleukin-33/ST2 signaling in left ventricular systolic dysfunction after acute myocardial infarction. JACC. Heart Failure, 3(1), 50-58. http://doi.org/10.1016/j.jchf.2014.07.015. PMid:25458175.
Lee, K.-N., Kim, D.-Y., Boo, K.-Y., Kim, Y.-G., Roh, S.-Y., Baek, Y.-S., Kim, D.-H., Lee, D. I., Shim, J., Choi, J.-I., Hwang, G.-S., & Kim, Y.-H. (2022). Therapeutic implications of galectin-3 in patients with atrial fibrillation. Scientific Reports, 12(1), 784. http://doi.org/10.1038/s41598-022-04894-9. PMid:35039576.
Ljungvall, I., Höglund, K., Tidholm, A., Olsen, L. H., Borgarelli, M., Venge, P., & Häggström, J. (2010). Cardiac troponin I is associated with severity of myxomatous mitral valve disease, age, and C-reactive protein in dogs. Journal of Veterinary Internal Medicine, 24(1), 153-159. http://doi.org/10.1111/j.1939-1676.2009.0428.x. PMid:20002554.
Rešetar Maslov, D., Farkaš, V., Rubić, I., Kuleš, J., Beletić, A., Beer Ljubić, B., Šmit, I., Mrljak, V., & Torti, M. (2023). Serum proteomic profiles reflect the stages of myxomatous mitral valve disease in dogs. International Journal of Molecular Sciences, 24(8), 7142. http://doi.org/10.3390/ijms24087142. PMid:37108311.
Rush, J. E., Lee, N. D., Freeman, L. M., & Brewer, B. (2006). C-reactive protein concentration in dogs with chronic valvular disease. Journal of Veterinary Internal Medicine, 20(3), 635-639. http://doi.org/10.1892/089 1-6640(2006)20[635:CPCIDW]2.0.CO;2. PMid:16734101.
Sabbah, H. N., Gupta, R. C., Singh-Gupta, V., Zhang, K., & Xu, J. (2016). Circulating level of the growth-differentiation factor-15 is increased in dogs with heart failure and normalized after long-term therapy with elamipretide. Circulation, 134(Suppl 1), A12980. http://doi.org/10.1161/circ.134.suppl_1.12980.
Sakarin, S., Rungsipipat, A., & Surachetpong, S. D. (2016). Galectin-3 in cardiac muscle and circulation of dogs with degenerative mitral valve disease. Journal of Veterinary Cardiology, 18(1), 34-46. http://doi.org/10.1016/j.jvc.2015.10.007. PMid:26786977.
Savic-Radojevic, A., Pljesa-Ercegovac, M., Matic, M., Simic, D., Radovanovic, S., & Simic, T. (2017). Novel biomarkers of heart failure. In G. S. Makowski (Ed.), Advances in Clinical Chemistry (Vol. 79, pp. 93-152). Elsevier. http://doi.org/10.1016/bs.acc.2016.09.002.
Seropian, I. M., Cassaglia, P., Miksztowicz, V., & González, G. E. (2023). Unraveling the role of galectin-3 in cardiac pathology and physiology. Frontiers in Physiology, 14, 1304735. http://doi.org/10.3389/fphys.2023.1304735. PMid:38170009.
Sharma, A., Stevens, S. R., Lucas, J., Fiuzat, M., Adams, K. F., Whellan, D. J., Donahue, M. P., Kitzman, D. W., Piña, I. L., Zannad, F., Kraus, W. E., O’Connor, C. M., & Felker, G. M. (2017). Utility of growth differentiation factor-15, a marker of oxidative stress and inflammation, in chronic heart failure: Insights from the HF-ACTION study. JACC. Heart Failure, 5(10), 724-734. http://doi.org/10.1016/j.jchf.2017.07.013. PMid:28958347.
Sygitowicz, G., Maciejak-Jastrzębska, A., & Sitkiewicz, D. (2021). The diagnostic and therapeutic potential of galectin-3 in cardiovascular diseases. Biomolecules, 12(1), 46. http://doi.org/10.3390/biom12010046. PMid:35053194.
Tarnow, I., Falk, T., Tidholm, A., Martinussen, T., Jensen, A. L., Olsen, L. H., Pedersen, H. D., & Kristensen, A. T. (2007). Hemostatic biomarkers in dogs with chronic congestive heart failure. Journal of Veterinary Internal Medicine, 21(3), 451-457. http://doi.org/10.1111/j.1939-1676.2007.tb02989.x. PMid:17552450.
Tarnow, I., Kristensen, A. T., Olsen, L. H., & Pedersen, H. D. (2004). Assessment of changes in hemostatic markers in Cavalier King Charles Spaniels with myxomatous mitral valve disease. American Journal of Veterinary Research, 65(12), 1644-1652. http://doi.org/10.2460/ajvr.2004.65.1644. PMid:15631028.
Teramoto, K., Nochioka, K., Sakata, Y., Kato, E. T., Nishimura, K., Shimokawa, H., & Yasuda, S., & SUPPORT Trial Investigators (2024). Growth differentiation factor-15 and metabolic features in chronic heart failure: Insights from the SUPPORT Trial-GDF15 across the BMI spectrum. International Journal of Cardiology, 407, 132093. http://doi.org/10.1016/j.ijcard.2024.132093. PMid:38663803.
Thomas, W. P. (1984). Two-dimensional, real-time echocardiography in the dog: Technique and anatomic validation. Veterinary Radiology & Ultrasound, 25(2), 50-64. http://doi.org/10.1111/j.1740-8261.1984.tb01910.x. Tilley, L. P., Smith, F. W. K., Sleeper, M. M., & Kraus, M. (Eds.) (2025). Manual of Canine and Feline Cardiology (6th ed.). Saunders.
Torrente, C., Manzanilla, E. G., Bosch, L., Fresno, L., Rivera Del Alamo, M., Andaluz, A., Saco, Y., & Ruiz de Gopegui, R. (2015). Plasma iron, C-reactive protein, albumin, and plasma fibrinogen concentrations in dogs with systemic inflammatory response syndrome. Journal of Veterinary Emergency and Critical Care (San Antonio, Tex.), 25(5), 611-619. http://doi.org/10.1111/vec.12340. PMid:26172578.
Welsh, P., Kimenai, D. M., Marioni, R. E., Hayward, C., Campbell, A., Porteous, D., Mills, N. L., O’Rahilly, S., & Sattar, N. (2022). Reference ranges for GDF-15, and risk factors associated with GDF-15, in a large general population cohort. Clinical Chemistry and Laboratory Medicine, 60(11), 1820-1829. http://doi.org/10.1515/cclm-2022-0135. PMid:35976089.
Xie, L., Xiao, H., Zhao, M., Tang, S., & Qiu, Y. (2024). Retrospective study on the short-term efficacy of different doses of spironolactone in patients with heart failure of ischemic cardiomyopathy and the influence of ventricular remodeling markers. American Journal of Cardiovascular Disease, 14(1), 21-28. http://doi.org/10.62347/SYIX9692. PMid:38495408.
Yancy, C. W., Jessup, M., Bozkurt, B., Butler, J., Casey Junior, D. E., Colvin, M. M., Drazner, M. H., Filippatos, G. S., Fonarow, G. C., Givertz, M. M., Hollenberg, S. M., Lindenfeld, J., Masoudi, F. A., McBride, P. E., Peterson, P. N., Stevenson, L. W., & Westlake, C. (2017). 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Journal of the American College of Cardiology, 70(6), 776-803. http://doi.org/10.1016/j.jacc.2017.04.025. PMid:28461007.
Yu, I. B.-Y., & Huang, H.-P. (2016). Prevalence and prognosis of anemia in dogs with degenerative mitral valve disease. BioMed Research International, 2016, 4727054. http://doi.org/10.1155/2016/4727054. PMid:27840827.
Zaborska, B., Sikora-Frąc, M., Smarż, K., Pilichowska-Paszkiet, E., Budaj, A., Sitkiewicz, D., & Sygitowicz, G. (2023). The role of Galectin-3 in heart failure—the diagnostic, prognostic and therapeutic potential—where do we stand? International Journal of Molecular Sciences, 24(17), 13111. http://doi.org/10.3390/ijms241713111. PMid:37685918.
Lok, S. I., Winkens, B., Goldschmeding, R., van Geffen, A. J. P., Nous, F. M. A., van Kuik, J., van der Weide, P., Klöpping, 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(11), 1249-1256. http://doi.org/10.1093/eurjhf/hfs120. PMid:22843564.
Malcolm, E. L., Visser, L. C., Phillips, K. L., & Johnson, L. R. (2018). Diagnostic value of vertebral left atrial size as determined from thoracic radiographs for assessment of left atrial size in dogs with myxomatous mitral valve disease. Journal of the American Veterinary Medical Association, 253(8), 1038-1045. http://doi.org/10.2460/javma.253.8.1038. PMid:30272515.
Meijers, W. C., Bayes-Genis, A., Mebazaa, A., Bauersachs, J., Cleland, J. G. F., Coats, A. J. S., Januzzi, J. L., Maisel, A. S., McDonald, K., Mueller, T., Richards, A. M., Seferovic, P., Mueller, C., & de Boer, R. A. (2021). Circulating heart failure biomarkers beyond natriuretic peptides: Review from the Biomarker Study Group of the Heart Failure Association (HFA), European Society of Cardiology (ESC). European Journal of Heart Failure, 23(10), 1610-1632. http://doi.org/10.1002/ejhf.2346. PMid:34498368.
Milting, H., Ellinghaus, P., Seewald, M., Cakar, H., Bohms, B., Kassner, A., Körfer, R., Klein, M., Krahn, T., Kruska, L., El Banayosy, A., & Kramer, F. (2008). Plasma biomarkers of myocardial fibrosis and remodeling in terminal heart failure patients supported by mechanical circulatory support devices. The Journal of Heart and Lung Transplantation, 27(6), 589-596. http://doi.org/10.1016/j.healun.2008.02.018. PMid:18503956.
Nicolle, A. P., Chetboul, V., Allerheiligen, T., Pouchelon, J.-L., Gouni, V., Tessier-Vetzel, D., Sampedrano, C. C., & Lefebvre, H. P. (2007). Azotemia and glomerular filtration rate in dogs with chronic valvular disease. Journal of Veterinary Internal Medicine, 21(5), 943-949. http://doi.org/10.1111/j.1939-1676.2007.tb03047.x. PMid:17939547.
Oyama, M. A., & Chittur, S. V. (2006). Genomic expression patterns of mitral valve tissues from dogs with degenerative mitral valve disease. American Journal of Veterinary Research, 67(8), 1307-1318. http://doi.org/10.2460/ajvr.67.8.1307. PMid:16881841.
Pieters, M., Ferreira, M., de Maat, M. P. M., & Ricci, C. (2021). Biomarker association with cardiovascular disease and mortality – The role of fibrinogen. A report from the NHANES study. Thrombosis Research, 198, 182-189. http://doi.org/10.1016/j.thromres.2020.12.009. PMid:33360152.
Polizopoulou, Z. S., Koutinas, C. K., Cerón, J. J., Tvarijonaviciute, A., Martínez‐Subiela, S., Dasopoulou, A., York, M. J., Roman, I. F., Gandhi, M., Patel, S., & O’Brien, P. J. (2015). Correlation of serum cardiac troponin I and acute phase protein concentrations with clinical staging in dogs with degenerative mitral valve disease. Veterinary Clinical Pathology, 44(3), 397-404. http://doi.org/10.1111/vcp.12278. PMid:26288324.
Pouchelon, J.-L., Atkins, C. E., Bussadori, C., Oyama, M. A., Vaden, S. L., Bonagura, J. D., Chetboul, V., Cowgill, L. D., Elliot, J., Francey, T., Grauer, G. F., Luis Fuentes, V., Moise, N. S., Polzin, D. J., Van Dongen, A. M., & Van Israël, N. (2015). Cardiovascular–renal axis disorders in the domestic dog and cat: A veterinary consensus statement. The Journal of Small Animal Practice, 56(9), 537-552. http://doi.org/10.1111/jsap.12387. PMid:26331869.
Prihirunkit, K., Sastravaha, A., Lekcharoensuk, C., & Chanloinapha, P. (2014). Hemostatic markers in congestive heart failure dogs with mitral valve disease. Journal of Veterinary Medicine, 2014, 589873. http://doi.org/10.1155/2014/589873. PMid:26464938.
Rauchhaus, M., Doehner, W., Francis, D. P., Davos, C., Kemp, M., Liebenthal, C., Niebauer, J., Hooper, J., Volk, H. D., Coats, A. J., & Anker, S. D. (2000). Plasma cytokine parameters and mortality in patients with chronic heart failure. Circulation, 102(25), 3060-3067. http://doi.org/10.1161/01.CIR.102.25.3060. PMid:11120695.
Reimann, M. J., Ljungvall, I., Hillström, A., Møller, J. E., Hagman, R., Falk, T., Höglund, K., Häggström, J., & Olsen, L. H. (2016). Increased serum C-reactive protein concentrations in dogs with congestive heart failure due to myxomatous mitral valve disease. Veterinary Journal (London, England: 1997), 209, 113-118. http://doi.org/10.1016/j.tvjl.2015.12.006. PMid:26831162.

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