Journal of Cardiovascular Translational Research

, Volume 8, Issue 9, pp 554–566 | Cite as

Serum Amyloid P-Component Prevents Cardiac Remodeling in Hypertensive Heart Disease

  • Stephen J. Horgan
  • Chris J. Watson
  • Nadia Glezeva
  • Pat Collier
  • Roisin Neary
  • Isaac J. Tea
  • Niamh Corrigan
  • Mark Ledwidge
  • Ken McDonald
  • John A. Baugh


The potential for serum amyloid P-component (SAP) to prevent cardiac remodeling and identify worsening diastolic dysfunction (DD) was investigated. The anti-fibrotic potential of SAP was tested in an animal model of hypertensive heart disease (spontaneously hypertensive rats treated with SAP [SHR − SAP] × 12 weeks). Biomarker analysis included a prospective study of 60 patients with asymptomatic progressive DD. Compared with vehicle-treated Wistar-Kyoto rats (WKY-V), the vehicle-treated SHRs (SHR-V) exhibited significant increases in left ventricular mass, perivascular collagen, cardiomyocyte size, and macrophage infiltration. SAP administration was associated with significantly lower left ventricular mass (p < 0.01), perivascular collagen (p < 0.01), and cardiomyocyte size (p < 0.01). Macrophage infiltration was significantly attenuated in the SHR-SAP group. Biomarker analysis showed significant decreases in SAP concentration over time in patients with progressive DD (p < 0.05). Our results indicate that SAP prevents cardiac remodeling by inhibiting recruitment of pro-fibrotic macrophages and that depleted SAP levels identify patients with advancing DD suggesting a role for SAP therapy.


Serum amyloid P-component Hypertensive heart disease Left ventricular remodeling Macrophages Spontaneously hypertensive rats 


Compliance with Ethical Standards

Sources of Funding

This work was supported by the Health Research Board of Ireland [Research Training Fellowship for Healthcare Professionals] and the Irish Heart Foundation [Noel Hickey Bursary].


Stephen Horgan reports receiving a government non-profit research training fellowship grant for healthcare professionals from the Health Research Board of the Irish Government. All authors disclose that the Heartbeat Trust received unrestricted educational and/or research grants from Pfizer, Merck Sharp and Dohme, A. Menarini, Alere, Roche, Takeda, Abbott, Servier and the European Commission Framework Programme 7 MEDIA Project. Mark Ledwidge and Kenneth McDonald report receiving speaking/consulting fees from Servier, Pfizer, Alere, Roche and Merck (all based in Ireland) and a government non-profit grant from the Health Research Board of the Irish Government. Mark Ledwidge is co-founder and shareholder of University spin-out Solvotrin Therapeutics which is developing aspirin/niacin prodrugs. Kenneth McDonald is a shareholder of Solvotrin.

Human Subjects/Informed Consent Statement

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

Animal Study

All institutional and national guidelines for the care and use of laboratory animals were followed and approved by the appropriate institutional committees.

Supplementary material

12265_2015_9661_MOESM1_ESM.docx (23 kb)
ESM 1 (DOCX 22 kb)


  1. 1.
    Levy, D., Murabito, J. M., Anderson, K. M., Christiansen, J. C., & Castelli, W. P. (1992). Echocardiographic left ventricular hypertrophy: clinical characteristics. The Framingham Heart Study. Clinical and Experimental Hypertension. Part A, 14(1–2), 85–97.CrossRefGoogle Scholar
  2. 2.
    Levy, D., Garrison, R. J., Savage, D. D., Kannel, W. B., & Castelli, W. P. (1990). Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. The New England Journal of Medicine, 322(22), 1561–1566. doi: 10.1056/NEJM199005313222203.CrossRefPubMedGoogle Scholar
  3. 3.
    Prugger, C., Keil, U., Wellmann, J., de Bacquer, D., de Backer, G., Ambrosio, G. B., et al. (2011). Blood pressure control and knowledge of target blood pressure in coronary patients across Europe: results from the EUROASPIRE III survey. Journal of Hypertension, 29(8), 1641–1648. doi: 10.1097/HJH.0b013e328348efa7.CrossRefPubMedGoogle Scholar
  4. 4.
    Kenchaiah, S., Evans, J. C., Levy, D., Wilson, P. W., Benjamin, E. J., Larson, M. G., et al. (2002). Obesity and the risk of heart failure. The New England Journal of Medicine, 347(5), 305–313. doi: 10.1056/NEJMoa020245.CrossRefPubMedGoogle Scholar
  5. 5.
    Dhingra, R., & Vasan, R. S. (2012). Diabetes and the risk of heart failure. Heart Failure Clinics, 8(1), 125–133. doi: 10.1016/j.hfc.2011.08.008.PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Lorell, B. H., & Carabello, B. A. (2000). Left ventricular hypertrophy: pathogenesis, detection, and prognosis. Circulation, 102(4), 470–479.CrossRefPubMedGoogle Scholar
  7. 7.
    Diez, J., Querejeta, R., Lopez, B., Gonzalez, A., Larman, M., & Martinez Ubago, J. L. (2002). Losartan-dependent regression of myocardial fibrosis is associated with reduction of left ventricular chamber stiffness in hypertensive patients. Circulation, 105(21), 2512–2517.CrossRefPubMedGoogle Scholar
  8. 8.
    Brilla, C. G., Funck, R. C., & Rupp, H. (2000). Lisinopril-mediated regression of myocardial fibrosis in patients with hypertensive heart disease. Circulation, 102(12), 1388–1393.CrossRefPubMedGoogle Scholar
  9. 9.
    Querejeta, R., Lopez, B., Gonzalez, A., Sanchez, E., Larman, M., Martinez Ubago, J. L., et al. (2004). Increased collagen type I synthesis in patients with heart failure of hypertensive origin: relation to myocardial fibrosis. Circulation, 110(10), 1263–1268. doi: 10.1161/01.CIR.0000140973.60992.9A.CrossRefPubMedGoogle Scholar
  10. 10.
    Nicoletti, A., & Michel, J. B. (1999). Cardiac fibrosis and inflammation: interaction with hemodynamic and hormonal factors. Cardiovascular Research, 41(3), 532–543.CrossRefPubMedGoogle Scholar
  11. 11.
    Barisione, C., Garibaldi, S., Ghigliotti, G., Fabbi, P., Altieri, P., Casale, M. C., et al. (2010). CD14CD16 monocyte subset levels in heart failure patients. Disease Markers, 28(2), 115–124. doi: 10.3233/DMA-2010-0691.PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Kai, H., Kuwahara, F., Tokuda, K., & Imaizumi, T. (2005). Diastolic dysfunction in hypertensive hearts: roles of perivascular inflammation and reactive myocardial fibrosis. Hypertension Research, 28(6), 483–490. doi: 10.1291/hypres.28.483.CrossRefPubMedGoogle Scholar
  13. 13.
    Watson, C. J., Ledwidge, M. T., Phelan, D., Collier, P., Byrne, J. C., Dunn, M. J., et al. (2011). Proteomic analysis of coronary sinus serum reveals leucine-rich alpha2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure. Circulation. Heart Failure, 4(2), 188–197. doi: 10.1161/CIRCHEARTFAILURE.110.952200.CrossRefPubMedGoogle Scholar
  14. 14.
    Lara-Pezzi, E., Menasche, P., Trouvin, J. H., Badimon, L., Ioannidis, J. P., Wu, J. C., et al. (2015). Guidelines for translational research in heart failure. Journal of Cardiovascular Translational Research, 8(1), 3–22. doi: 10.1007/s12265-015-9606-8.CrossRefPubMedGoogle Scholar
  15. 15.
    Gopal, D. M., & Sam, F. (2013). New and emerging biomarkers in left ventricular systolic dysfunction--insight into dilated cardiomyopathy. Journal of Cardiovascular Translational Research, 6(4), 516–527. doi: 10.1007/s12265-013-9462-3.PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Botto, M., Hawkins, P. N., Bickerstaff, M. C., Herbert, J., Bygrave, A. E., McBride, A., et al. (1997). Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene. Nature Medicine, 3(8), 855–859.CrossRefPubMedGoogle Scholar
  17. 17.
    Togashi, S., Lim, S. K., Kawano, H., Ito, S., Ishihara, T., Okada, Y., et al. (1997). Serum amyloid P component enhances induction of murine amyloidosis. Laboratory Investigation, 77(5), 525–531.PubMedGoogle Scholar
  18. 18.
    Murakami, T., Yi, S., Maeda, S., Tashiro, F., Yamamura, K., Takahashi, K., et al. (1992). Effect of serum amyloid P component level on transthyretin-derived amyloid deposition in a transgenic mouse model of familial amyloidotic polyneuropathy. The American Journal of Pathology, 141(2), 451–456.PubMedCentralPubMedGoogle Scholar
  19. 19.
    Inoue, S., Kawano, H., Ishihara, T., Maeda, S., & Ohno, S. (2005). Formation of experimental murine AA amyloid fibrils in SAP-deficient mice: high resolution ultrastructural study. Amyloid, 12(3), 157–163. doi: 10.1080/13506120500232010.
  20. 20.
    Halushka, M. K., Eng, G., Collins, A. B., Judge, D. P., Semigran, M. J., & Stone, J. R. (2015). Optimization of serum immunoglobulin free light chain analysis for subclassification of cardiac amyloidosis. Journal of Cardiovascular Translational Research, 8(4), 264–268. doi: 10.1007/s12265-015-9628-2.CrossRefPubMedGoogle Scholar
  21. 21.
    Damy, T., Judge, D. P., Kristen, A. V., Berthet, K., Li, H., & Aarts, J. (2015). Cardiac findings and events observed in an open-label clinical trial of tafamidis in patients with non-Val30Met and non-Val122Ile hereditary transthyretin amyloidosis. Journal of Cardiovascular Translational Research, 8(2), 117–127. doi: 10.1007/s12265-015-9613-9.PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Haudek, S. B., Xia, Y., Huebener, P., Lee, J. M., Carlson, S., Crawford, J. R., et al. (2006). Bone marrow-derived fibroblast precursors mediate ischemic cardiomyopathy in mice. Proceedings of the National Academy of Sciences of the United States of America, 103(48), 18284–18289. doi: 10.1073/pnas.0608799103.PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Pilling, D., Roife, D., Wang, M., Ronkainen, S. D., Crawford, J. R., Travis, E. L., et al. (2007). Reduction of bleomycin-induced pulmonary fibrosis by serum amyloid P. Journal of Immunology, 179(6), 4035–4044.CrossRefGoogle Scholar
  24. 24.
    Murray, L. A., Rosada, R., Moreira, A. P., Joshi, A., Kramer, M. S., Hesson, D. P., et al. (2010). Serum amyloid P therapeutically attenuates murine bleomycin-induced pulmonary fibrosis via its effects on macrophages. PloS One, 5(3), e9683. doi: 10.1371/journal.pone.0009683.PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Castano, A. P., Lin, S. L., Surowy, T., Nowlin, B. T., Turlapati, S. A., Patel, T., et al. (2009). Serum amyloid P inhibits fibrosis through Fc gamma R-dependent monocyte-macrophage regulation in vivo. Science Translational Medicine, 1(5), 5ra13. doi: 10.1126/scitranslmed.3000111.PubMedCentralCrossRefPubMedGoogle Scholar
  26. 26.
    Murray, L. A., Kramer, M. S., Hesson, D. P., Watkins, B. A., Fey, E. G., Argentieri, R. L., et al. (2010). Serum amyloid P ameliorates radiation-induced oral mucositis and fibrosis. Fibrogenesis & Tissue Repair, 3, 11. doi: 10.1186/1755-1536-3-11.CrossRefGoogle Scholar
  27. 27.
    Westermann, D., Lindner, D., Kasner, M., Zietsch, C., Savvatis, K., Escher, F., et al. (2011). Cardiac inflammation contributes to changes in the extracellular matrix in patients with heart failure and normal ejection fraction. Circulation. Heart Failure, 4(1), 44–52. doi: 10.1161/CIRCHEARTFAILURE.109.931451.CrossRefPubMedGoogle Scholar
  28. 28.
    Jenny, N. S., Arnold, A. M., Kuller, L. H., Tracy, R. P., & Psaty, B. M. (2007). Serum amyloid P and cardiovascular disease in older men and women: results from the Cardiovascular Health Study. Arteriosclerosis, Thrombosis, and Vascular Biology, 27(2), 352–358. doi: 10.1161/01.ATV.0000254150.97741.fe.CrossRefPubMedGoogle Scholar
  29. 29.
    Murray, L. A., Chen, Q., Kramer, M. S., Hesson, D. P., Argentieri, R. L., Peng, X., et al. (2011). TGF-beta driven lung fibrosis is macrophage dependent and blocked by serum amyloid P. The International Journal of Biochemistry & Cell Biology, 43(1), 154–162. doi: 10.1016/j.biocel.2010.10.013.CrossRefGoogle Scholar
  30. 30.
    Lopez, B., Gonzalez, A., Querejeta, R., Larman, M., & Diez, J. (2006). Alterations in the pattern of collagen deposition may contribute to the deterioration of systolic function in hypertensive patients with heart failure. Journal of the American College of Cardiology, 48(1), 89–96. doi: 10.1016/j.jacc.2006.01.077.CrossRefPubMedGoogle Scholar
  31. 31.
    Peng, H., Carretero, O. A., Vuljaj, N., Liao, T. D., Motivala, A., Peterson, E. L., et al. (2005). Angiotensin-converting enzyme inhibitors: a new mechanism of action. Circulation, 112(16), 2436–2445. doi: 10.1161/CIRCULATIONAHA.104.528695.CrossRefPubMedGoogle Scholar
  32. 32.
    Gao, S., Long, C. L., Wang, R. H., & Wang, H. (2009). K(ATP) activation prevents progression of cardiac hypertrophy to failure induced by pressure overload via protecting endothelial function. Cardiovascular Research, 83(3), 444–456. doi: 10.1093/cvr/cvp099.CrossRefPubMedGoogle Scholar
  33. 33.
    Xiang, W., Kong, J., Chen, S., Cao, L. P., Qiao, G., Zheng, W., et al. (2005). Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems. American Journal of Physiology. Endocrinology and Metabolism, 288(1), E125–132. doi: 10.1152/ajpendo.00224.2004.CrossRefPubMedGoogle Scholar
  34. 34.
    He, H. B., Yang, X. Z., Shi, M. Q., Zeng, X. W., Wu, L. M., & Li, L. D. (2008). Comparison of cardioprotective effects of salvianolic acid B and benazepril on large myocardial infarction in rats. Pharmacological Reports, 60(3), 369–381.PubMedGoogle Scholar
  35. 35.
    Ledwidge, M., Gallagher, J., Conlon, C., Tallon, E., O'Connell, E., Dawkins, I., et al. (2013). Natriuretic peptide-based screening and collaborative care for heart failure: the STOP-HF randomized trial. JAMA, 310(1), 66–74. doi: 10.1001/jama.2013.7588.CrossRefPubMedGoogle Scholar
  36. 36.
    Collier, P., Watson, C. J., Waterhouse, D. F., Dawkins, I. R., Patle, A. K., Horgan, S., et al. (2012). Progression of left atrial volume index in a population at risk for heart failure: a substudy of the STOP-HF (St Vincent's Screening TO Prevent Heart Failure) trial. European Journal of Heart Failure, 14(9), 957–964. doi: 10.1093/eurjhf/hfs084.CrossRefPubMedGoogle Scholar
  37. 37.
    Horgan, S., Watson, C., Glezeva, N., & Baugh, J. (2014). Murine models of diastolic dysfunction and heart failure with preserved ejection fraction. Journal of Cardiac Failure, 20(12), 984–995. doi: 10.1016/j.cardfail.2014.09.001.CrossRefPubMedGoogle Scholar
  38. 38.
    Palmieri, V., Dahlof, B., DeQuattro, V., Sharpe, N., Bella, J. N., de Simone, G., et al. (1999). Reliability of echocardiographic assessment of left ventricular structure and function: the PRESERVE study. Prospective randomized study evaluating regression of ventricular enlargement. Journal of the American College of Cardiology, 34(5), 1625–1632.CrossRefPubMedGoogle Scholar
  39. 39.
    Verdecchia, P., Schillaci, G., Borgioni, C., Ciucci, A., Gattobigio, R., Zampi, I., et al. (1998). Prognostic significance of serial changes in left ventricular mass in essential hypertension. Circulation, 97(1), 48–54.CrossRefPubMedGoogle Scholar
  40. 40.
    Kuwahara, F., Kai, H., Tokuda, K., Takeya, M., Takeshita, A., Egashira, K., et al. (2004). Hypertensive myocardial fibrosis and diastolic dysfunction: another model of inflammation? Hypertension, 43(4), 739–745. doi: 10.1161/01.HYP.0000118584.33350.7d.CrossRefPubMedGoogle Scholar
  41. 41.
    Melendez, G. C., McLarty, J. L., Levick, S. P., Du, Y., Janicki, J. S., & Brower, G. L. (2010). Interleukin 6 mediates myocardial fibrosis, concentric hypertrophy, and diastolic dysfunction in rats. Hypertension, 56(2), 225–231. doi: 10.1161/HYPERTENSIONAHA.109.148635.PubMedCentralCrossRefPubMedGoogle Scholar
  42. 42.
    Hermida, N., Lopez, B., Gonzalez, A., Dotor, J., Lasarte, J. J., Sarobe, P., et al. (2009). A synthetic peptide from transforming growth factor-beta1 type III receptor prevents myocardial fibrosis in spontaneously hypertensive rats. Cardiovascular Research, 81(3), 601–609. doi: 10.1093/cvr/cvn315.CrossRefPubMedGoogle Scholar
  43. 43.
    Lecomte, D., Fornes, P., Fouret, P., & Nicolas, G. (1993). Isolated myocardial fibrosis as a cause of sudden cardiac death and its possible relation to myocarditis. Journal of Forensic Sciences, 38(3), 617–621.CrossRefPubMedGoogle Scholar
  44. 44.
    Partemi, S., Batlle, M., Berne, P., Berruezo, A., Campos, B., Mont, L., et al. (2013). Analysis of the arrhythmogenic substrate in human heart failure. Cardiovascular Pathology, 22(2), 133–140. doi: 10.1016/j.carpath.2012.07.003.CrossRefPubMedGoogle Scholar
  45. 45.
    Palomer, X., Salvado, L., Barroso, E., & Vazquez-Carrera, M. (2013). An overview of the crosstalk between inflammatory processes and metabolic dysregulation during diabetic cardiomyopathy. International Journal of Cardiology. doi: 10.1016/j.ijcard.2013.07.150.Google Scholar
  46. 46.
    Huang, C. Y., Kuo, W. W., Chueh, P. J., Tseng, C. T., Chou, M. Y., & Yang, J. J. (2004). Transforming growth factor-beta induces the expression of ANF and hypertrophic growth in cultured cardiomyoblast cells through ZAK. Biochemical and Biophysical Research Communications, 324(1), 424–431. doi: 10.1016/j.bbrc.2004.09.067.CrossRefPubMedGoogle Scholar
  47. 47.
    Lovett, D. H., Mahimkar, R., Raffai, R. L., Cape, L., Zhu, B. Q., Jin, Z. Q., et al. (2013). N-terminal truncated intracellular matrix metalloproteinase-2 induces cardiomyocyte hypertrophy, inflammation and systolic heart failure. PloS One, 8(7), e68154. doi: 10.1371/journal.pone.0068154.PubMedCentralCrossRefPubMedGoogle Scholar
  48. 48.
    Tsai, H. H., Frost, E., To, V., Robinson, S., Ffrench-Constant, C., Geertman, R., et al. (2002). The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. Cell, 110(3), 373–383.CrossRefPubMedGoogle Scholar
  49. 49.
    Haghnegahdar, H., Du, J., Wang, D., Strieter, R. M., Burdick, M. D., Nanney, L. B., et al. (2000). The tumorigenic and angiogenic effects of MGSA/GRO proteins in melanoma. Journal of Leukocyte Biology, 67(1), 53–62.PubMedCentralPubMedGoogle Scholar
  50. 50.
    Carr, M. W., Roth, S. J., Luther, E., Rose, S. S., & Springer, T. A. (1994). Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant. Proceedings of the National Academy of Sciences of the United States of America, 91(9), 3652–3656.PubMedCentralCrossRefPubMedGoogle Scholar
  51. 51.
    Xu, L. L., Warren, M. K., Rose, W. L., Gong, W., & Wang, J. M. (1996). Human recombinant monocyte chemotactic protein and other C-C chemokines bind and induce directional migration of dendritic cells in vitro. Journal of Leukocyte Biology, 60(3), 365–371.PubMedGoogle Scholar
  52. 52.
    Schupp, N., Kolkhof, P., Queisser, N., Gartner, S., Schmid, U., Kretschmer, A., et al. (2011). Mineralocorticoid receptor-mediated DNA damage in kidneys of DOCA-salt hypertensive rats. The FASEB Journal, 25(3), 968–978. doi: 10.1096/fj.10-173286.CrossRefPubMedGoogle Scholar
  53. 53.
    Glezeva, N., Collier, P., Voon, V., Ledwidge, M., McDonald, K., Watson, C., et al. (2013). Attenuation of monocyte chemotaxis—a novel anti-inflammatory mechanism of action for the cardio-protective hormone B-type natriuretic peptide. Journal of Cardiovascular Translational Research, 6(4), 545–557. doi: 10.1007/s12265-013-9456-1.CrossRefPubMedGoogle Scholar
  54. 54.
    Chiba, T., Itoh, T., Tabuchi, M., Nakazawa, T., & Satou, T. (2012). Interleukin-1beta accelerates the onset of stroke in stroke-prone spontaneously hypertensive rats. Mediators of Inflammation, 2012, 701976. doi: 10.1155/2012/701976.PubMedCentralCrossRefPubMedGoogle Scholar
  55. 55.
    Miguel-Carrasco, J. L., Zambrano, S., Blanca, A. J., Mate, A., & Vazquez, C. M. (2010). Captopril reduces cardiac inflammatory markers in spontaneously hypertensive rats by inactivation of NF-kB. Journal of Inflammation (London), 7, 21. doi: 10.1186/1476-9255-7-21.CrossRefGoogle Scholar
  56. 56.
    Johnson, M. L., Ely, D. L., & Turner, M. E. (1992). Genetic divergence between the Wistar-Kyoto rat and the spontaneously hypertensive rat. Hypertension, 19(5), 425–427.CrossRefPubMedGoogle Scholar
  57. 57.
    Ristow, B., Ali, S., Whooley, M. A., & Schiller, N. B. (2008). Usefulness of left atrial volume index to predict heart failure hospitalization and mortality in ambulatory patients with coronary heart disease and comparison to left ventricular ejection fraction (from the Heart and Soul Study). The American Journal of Cardiology, 102(1), 70–76. doi: 10.1016/j.amjcard.2008.02.099.PubMedCentralCrossRefPubMedGoogle Scholar
  58. 58.
    Tamura, H., Watanabe, T., Nishiyama, S., Sasaki, S., Arimoto, T., Takahashi, H., et al. (2011). Increased left atrial volume index predicts a poor prognosis in patients with heart failure. Journal of Cardiac Failure, 17(3), 210–216. doi: 10.1016/j.cardfail.2010.10.006.CrossRefPubMedGoogle Scholar
  59. 59.
    Takemoto, Y., Barnes, M. E., Seward, J. B., Lester, S. J., Appleton, C. A., Gersh, B. J., et al. (2005). Usefulness of left atrial volume in predicting first congestive heart failure in patients > or =65 years of age with well-preserved left ventricular systolic function. The American Journal of Cardiology, 96(6), 832–836. doi: 10.1016/j.amjcard.2005.05.031.CrossRefPubMedGoogle Scholar
  60. 60.
    Tsang, T. S., Abhayaratna, W. P., Barnes, M. E., Miyasaka, Y., Gersh, B. J., Bailey, K. R., et al. (2006). Prediction of cardiovascular outcomes with left atrial size: is volume superior to area or diameter? Journal of the American College of Cardiology, 47(5), 1018–1023. doi: 10.1016/j.jacc.2005.08.077.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Stephen J. Horgan
    • 1
    • 2
  • Chris J. Watson
    • 1
    • 2
  • Nadia Glezeva
    • 1
    • 2
  • Pat Collier
    • 1
    • 2
    • 3
  • Roisin Neary
    • 1
  • Isaac J. Tea
    • 1
  • Niamh Corrigan
    • 1
  • Mark Ledwidge
    • 1
    • 2
  • Ken McDonald
    • 1
    • 2
  • John A. Baugh
    • 1
  1. 1.UCD Conway Institute of Biomolecular and Biomedical Research, UCD School of MedicineUniversity College DublinDublinIreland
  2. 2.Chronic Cardiovascular Disease UnitSt. Vincent’s University HospitalDublin 4Ireland
  3. 3.Cardiovascular MedicineCleveland ClinicClevelandUSA

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