Characteristics of Cobalt-Related Cardiomyopathy in Metal Hip Implant Patients: An Evaluation of 15 Published Reports

Abstract

Over 300,000 hip replacements occurred in the USA in 2010, and the frequency is likely increasing annually. Blood Cobalt (Co) concentrations in patients with well-functioning cobalt–chromium (Co–Cr) hip implants are usually elevated above background concentrations relative to the general population. Excessive Co exposure, in rare cases, can result in cardiomyopathy. The purpose of this review was to identify cases of cardiomyopathy in metal-containing hip implant patients and to evaluate the possible cause of each patient’s cardiomyopathy. We evaluated 15 cases published between 2009 and 2016, and, based on a review of the preexisting risk factors, blood Co concentrations, and histopathological information published for each patient, they were stratified into one of four categories regarding the association between Co exposure and the development of cardiomyopathy: (1) Co was causal (five cases); (2) Co was contributory (two cases); (3) Co was possibly contributory (six cases); and (4) Co was non-causal (two cases). In all 15 cases, blood Co concentrations (14–6521 μg/L) were elevated beyond levels associated with the majority of metal-containing implant patients (0.1–10 μg/L), and, in many cases, there was evidence of a malfunctioning implant. The data indicate that individuals with well-functioning implants, even those with preexisting risk factors, are at no risk of developing cardiac effects. We conclude that blood Co measurements are informative, but should be interpreted with caution, and in context of other factors evaluated in this analysis. The mere presence of elevated Co is not sufficient to indicate causation for a patient’s cardiomyopathy.

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References

  1. 1.

    Barborik, M., & Dusek, J. (1972). Cardiomyopathy accompanying industrial cobalt exposure. British Heart Journal, 34, 113–116.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. 2.

    Alpert, M. A., Fraley, M. A., Birchem, J. A., & Senkottaiyan, N. (2005). Management of obesity cardiomyopathy. Expert Review of Cardiovascular Therapy, 3, 225–230.

    Article  PubMed  Google Scholar 

  3. 3.

    Boudina, S., & Abel, E. D. (2007). Diabetic cardiomyopathy revisited. Circulation, 115, 3213–3223.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Patel, S. R., D’Alessandro, D., & Shin, J. J. (2012). Combined heart and liver transplantation in an adult with familial heterozygous hypercholesterolemia and severe ischemic cardiomyopathy. Journal of Heart and Lung Transplantation, 31, 229.

    Article  PubMed  Google Scholar 

  5. 5.

    Alhaj, E., Alhaj, N., Rahman, I., Niazi, T. O., Berkowitz, R., & Klapholz, M. (2013). Uremic cardiomyopathy: An underdiagnosed disease. Congestive Heart Failure, 19, E40–E45.

    Article  PubMed  Google Scholar 

  6. 6.

    Allen, L. A., Ambardekar, A. V., Devaraj, K. M., Maleszewski, J. J., & Wolfel, E. E. (2014). Clinical problem-solving. Missing elements of the history. New England Journal of Medicine, 370, 559–566.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. 7.

    Dahms, K., Sharkova, Y., Heitland, P., Pankuweit, S., & Schaefer, J. R. (2014). Cobalt intoxication diagnosed with the help of Dr. House. Lancet, 383, 574.

    Article  PubMed  Google Scholar 

  8. 8.

    Machado, C., Appelbe, A., & Wood, R. (2012). Arthroprosthetic cobaltism and cardiomyopathy. Heart, Lung and Circulation, 21, 759–760.

    Article  PubMed  Google Scholar 

  9. 9.

    Samar, H. Y., Doyle, M., Williams, R. B., Yamrozik, J. A., Bunker, M., Biederman, R. W., et al. (2015). Novel use of cardiac magnetic resonance imaging for the diagnosis of cobalt cardiomyopathy. JACC Cardiovascular Imaging, 8, 1231–1232.

    Article  PubMed  Google Scholar 

  10. 10.

    Vasukutty, N. L., & Minhas, T. H. (2016). Systemic effects of cobalt toxicity after revision hip replacement can manifest in intermediate to long term follow-up. Hip International the Journal of Clinical and Experimental Research on Hip Pathology and Therapy, 26, e31–e34.

    PubMed  Google Scholar 

  11. 11.

    Maron, B. J., Towbin, J. A., Thiene, G., Antzelevitch, C., Corrado, D., Arnett, D., et al. (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.

    Article  PubMed  Google Scholar 

  12. 12.

    Wexler, R. K., Elton, T., Pleister, A., & Feldman, D. (2009). Cardiomyopathy: An overview. American Family Physician, 79, 778–784.

    PubMed  PubMed Central  Google Scholar 

  13. 13.

    Mentz, R. J., & O’Connor, C. M. (2016). Pathophysiology and clinical evaluation of acute heart failure. Nature Reviews Cardiology, 13, 28–35.

    Article  PubMed  CAS  Google Scholar 

  14. 14.

    Burke, A. P. & Butany, J. (2015). Dilated Cardiomyopathy pathology. November 4, 2015. Accessed August 29, 2016 http://emedicine.medscape.com/article/2017823-overview.

  15. 15.

    Gersh, B. J., Maron, B. J., Bonow, R. O., Dearani, J. A., Fifer, M. A., Link, M. S., et al. (2011). 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation, 124, e783–e831.

    Article  PubMed  Google Scholar 

  16. 16.

    NIH. (2016). How is cardiomyopathy diagnosed? June 22, 2016. Accessed August 29, 2016 https://www.nhlbi.nih.gov/health/health-topics/topics/cm/diagnosis.

  17. 17.

    AHA. (2016). Symptoms and diagnosis of cardiomyopathy. April 8, 2016. Accessed August 29, 2016 https://www.heart.org/HEARTORG/Conditions/More/Cardiomyopathy/Symptoms-and-Diagnosis-of-Cardiomyopathy_UCM_444175_Article.jsp#.V3QPr032blY.

  18. 18.

    Mayo Clinic. (2015). Cardiomyopathy tests and diagnosis. March 17, 2015. Accessed August 29, 2016 http://www.mayoclinic.org/diseases-conditions/cardiomyopathy/basics/tests-diagnosis/con-20026819.

  19. 19.

    Finley, B. L., Monnot, A. D., Gaffney, S. H., & Paustenbach, D. J. (2012). Dose-response relationships for blood cobalt concentrations and health effects: A review of the literature and application of a biokinetic model. Journal of Toxicology and Environmental Health, Part B, 15, 493–523.

    Article  CAS  Google Scholar 

  20. 20.

    Morin, Y., & Daniel, P. (1967). Quebec beer-drinkers’ cardiomyopathy: Etiological considerations. Canadian Medical Association Journal, 97, 926–928.

    PubMed  PubMed Central  CAS  Google Scholar 

  21. 21.

    Centeno, J., Pestaner, J., Mullick, F., & Virmani, R. (1996). An analytical comparison of cobalt cardiomyopathy and idiopathic dilated cardiomyopathy. Biological Trace Element Research, 55, 21–30.

    Article  PubMed  CAS  Google Scholar 

  22. 22.

    Paustenbach, D. J., Galbraith, D. A., & Finley, B. L. (2014). Interpreting cobalt blood concentrations in hip implant patients. Clinical Toxicology, 52, 98–112.

    Article  PubMed  CAS  Google Scholar 

  23. 23.

    Unice, K. M., Kerger, B. D., Paustenbach, D. J., Finley, B. L., & Tvermoes, B. E. (2014). Refined biokinetic model for humans exposed to cobalt dietary supplements and other sources of systemic cobalt exposure. Chemico-Biological Interactions, 216, 53–74.

    Article  PubMed  CAS  Google Scholar 

  24. 24.

    Packer, M. (2016). Cobalt cardiomyopathy: A critical reappraisal in light of a recent resurgence. Circulation: Heart failure, 9, e003604.

    Google Scholar 

  25. 25.

    Smith-Petersen, M. N. (1948). Evolution of mould arthroplasty of the hip joint. Journal of Bone and Joint Surgery, 30, 59–75.

    Article  Google Scholar 

  26. 26.

    McKee, G. K., & Watson-Farrar, J. (1966). Replacement of arthritic hips by the McKee–Farrar prosthesis. Journal of Bone and Joint Surgery, 48, 245–259.

    Article  PubMed  CAS  Google Scholar 

  27. 27.

    Kovochich, M., Fung, E. S., Donovan, E., Unice, K. M., Paustenbach, D. J., & Finley, B. L. (2017). Characterization of wear debris from metal-on-metal hip implants during normal wear versus edge-loading conditions. Journal of Biomedical Materials Research, Part B, Applied Biomaterials. https://doi.org/10.1002/jbm.b.33902.

    PubMed  Article  Google Scholar 

  28. 28.

    Jacobs, J. J., Urban, R. M., Gilbert, J. L., Skipor, A. K., Black, J., Jasty, M., et al. (1995). Local and distant products from modularity. Clinical Orthopaedics, 319, 94–105.

    Google Scholar 

  29. 29.

    Morlock, M. M., Bishop, N., Zustin, J., Hahn, M., Ruther, W., & Amling, M. (2008). Modes of implant failure after hip resurfacing: Morphological and wear analysis of 267 retrieval specimens. Journal of Bone and Joint Surgery, 90(Suppl 3), 89–95.

    Article  PubMed  Google Scholar 

  30. 30.

    Catelas, I., Bobyn, J. D., Medley, J. B., Krygier, J. J., Zukor, D. J., & Huk, O. L. (2003). Size, shape, and composition of wear particles from metal-metal hip simulator testing: Effects of alloy and number of loading cycles. Journal of Biomedical Materials Research Part A, 67, 312–327.

    Article  PubMed  CAS  Google Scholar 

  31. 31.

    Engh, C. A., Jr., MacDonald, S., Sritulanondha, S., Thompson, A., Naudie, D., & Engh, C. (2009). Metal ion levels after metal-on-metal total hip arthroplasty: A randomized trial. Clinical Orthopaedics, 467, 101–111.

    Article  Google Scholar 

  32. 32.

    Walter, L. R., Marel, E., Harbury, R., & Wearne, J. (2008). Distribution of chromium and cobalt ions in various blood fractions after resurfacing hip arthroplasty. Journal of Arthroplasty, 23, 814–821.

    Article  PubMed  Google Scholar 

  33. 33.

    Sidaginamale, R. P., Joyce, T. J., Lord, J. K., Jefferson, R., Blain, P. G., Nargol, A. V., et al. (2013). Blood metal ion testing is an effective screening tool to identify poorly performing metal-on-metal bearing surfaces. Bone and Joint Research, 2, 84–95.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. 34.

    Van Der Straeten, C., Grammatopoulos, G., Gill, H. S., Calistri, A., Campbell, P., & De Smet, K. A. (2013). The 2012 Otto Aufranc Award: The interpretation of metal ion levels in unilateral and bilateral hip resurfacing. Clinical Orthopaedics, 471, 377–385.

    Article  Google Scholar 

  35. 35.

    Tvermoes, B. E., Paustenbach, D. J., Kerger, B. D., Finley, B. L., & Unice, K. M. (2015). Review of cobalt toxicokinetics following oral dosing: Implications for health risk assessments and metal-on-metal hip implant patients. Critical Reviews in Toxicology, 45, 367–387.

    Article  PubMed  CAS  Google Scholar 

  36. 36.

    Hartmann, A., Hannemann, F., Lutzner, J., Seidler, A., Drexler, H., Gunther, K. P., et al. (2013). Metal ion concentrations in body fluids after implantation of hip replacements with metal-on-metal bearing: Systematic review of clinical and epidemiological studies. PLoS ONE, 8, e70359–e70384.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. 37.

    Alimonti, A., Bocca, B., Mannella, E., Petrucci, F., Zennaro, F., Cotichini, R., et al. (2005). Assessment of reference values for selected elements in a healthy urban population. Annali dell Istituto Superiore di Sanita, 41, 181–187.

    PubMed  CAS  Google Scholar 

  38. 38.

    Cobb, A., & Schmalzreid, T. (2006). The clinical significance of metal ion release from cobalt-chromium metal-on-metal hip joint arthroplasty. Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, 220, 385–398.

    Article  CAS  Google Scholar 

  39. 39.

    MacDonald, S. J. (2004). Can a safe level for metal ions in patients with metal-on-metal total hip arthroplasties be determined? Journal of Arthroplasty, 19, 71–77.

    Article  PubMed  Google Scholar 

  40. 40.

    van Lingen, C. P., Ettema, H. B., Timmer, J. R., de Jong, G., & Verheyen, C. C. (2013). Clinical manifestations in ten patients with asymptomatic metal-on-metal hip arthroplasty with very high cobalt levels. Hip International, 23, 441–444.

    Article  PubMed  Google Scholar 

  41. 41.

    Prentice, J. R., Clark, M. J., Hoggard, N., Morton, A. C., Tooth, C., Paley, M. N., et al. (2013). Metal-on-metal hip prostheses and systemic health: A cross-sectional association study 8 years after implantation. PLoS ONE, 8, e66186–e66195.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. 42.

    Berber, R., Abdel-Gadir, A., Rosmini, S., Captur, G., Nordin, S., Culotta, V., et al. (2017). Assessing for cardiotoxicity from metal-on-metal hip implants with advanced multimodality imaging techniques. JBJS, 99(21), 1827–1835.

    Google Scholar 

  43. 43.

    Leslie, I. J., Williams, S., Isaac, G., Ingham, E., & Fisher, J. (2009). High cup angle and microseparation increase the wear of hip surface replacements. Clinical Orthopaedics, 467, 2259–2265.

    Article  Google Scholar 

  44. 44.

    De Haan, R., Pattyn, C., Gill, H. S., Murray, D. W., Campbell, P. A., & De Smet, K. (2008). Correlation between inclination of the acetabular component and metal ion levels in metal-on-metal hip resurfacing replacement. Journal of Bone and Joint Surgery, 90, 1291–1297.

    Article  PubMed  Google Scholar 

  45. 45.

    Gilbert, C. J., Cheung, A., Butany, J., Zywiel, M. G., Syed, K., McDonald, M., et al. (2013). Hip pain and heart failure: The missing link. Canadian Journal of Cardiology, 29, 639.e631–639.e632.

    Article  Google Scholar 

  46. 46.

    Zywiel, M. G., Brandt, J. M., Overgaard, C. B., Cheung, A. C., Turgeon, T. R., & Syed, K. A. (2013). Fatal cardiomyopathy after revision total hip replacement for fracture of a ceramic liner. Bone and Joint Journal, 95, 31–37.

    Article  PubMed  Google Scholar 

  47. 47.

    Oldenburg, M., Wegner, R., & Baur, X. (2009). Severe cobalt intoxication due to prosthesis wear in repeated total hip arthroplasty. The Journal of Arthroplasty, 24, 20.

    Article  Google Scholar 

  48. 48.

    Weber, K. P., Schweier, C., Kana, V., Guggi, T., Byber, K., & Landau, K. (2014). Wear and tear vision. In North American Neuro-Ophthalmology Society (Ed.), 2014 Annual Meeting of the North American Neuro-Ophthalmology Society (pp. 37–38). Minneapolis, MN: North American Neuro-Ophthalmology Society.

    Google Scholar 

  49. 49.

    Martin, J. R., Spencer-Gardner, L., Camp, C. L., Stulak, J. M., & Sierra, R. J. (2015). Cardiac cobaltism: A rare complication after bilateral metal-on-metal total hip arthroplasty. Arthroplasty Today, 1, 99–102.

    Article  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Fox, K. A., Phillips, T. M., Yanta, J. H., & Abesamis, M. G. (2016). Fatal cobalt toxicity after total hip arthroplasty revision for fractured ceramic components. Clinical Toxicology, 54, 874–877.

    Article  PubMed  CAS  Google Scholar 

  51. 51.

    Pelclova, D., Sklensky, M., Janicek, P., & Lach, K. (2012). Severe cobalt intoxication following hip replacement revision: Clinical features and outcome. Clinical Toxicology, 50, 262–265.

    Article  PubMed  CAS  Google Scholar 

  52. 52.

    Khan, A. H., Verma, R., Bajpai, A., & Mackey-Bojack, S. (2015). Unusual case of congestive heart failure: Cardiac magnetic resonance imaging and histopathologic findings in cobalt cardiomyopathy. Circulation: Cardiovascular Imaging, 8, e003352.

    Google Scholar 

  53. 53.

    Mosier, B. A., Maynard, L., Sotereanos, N. G., & Sewecke, J. J. (2016). Progressive cardiomyopathy in a patient with elevated cobalt ion levels and bilateral metal-on-metal hip arthroplasties. American Journal of Orthopedics, 45, E132–E135.

    PubMed  Google Scholar 

  54. 54.

    Giampreti, A., Lonati, D., & Locatelli, C. A. (2014). Reply to letter by Devlin et al.-Chelation in suspected prosthetic hip-associated cobalt toxicity. Canadian Journal of Cardiology, 30(465), e413.

    Google Scholar 

  55. 55.

    Giampreti, A., Lonati, D., Vecchio, R., Petrolini, V., Basso, V., Zerbini, F., et al. (2014). Abstract 244: Chelation therapy with intravenous high dose N-acetyl-cysteine for cobalt release from metal on metal hip replacement—A first case report. Clinical Toxicology, 51, 361–363.

    Google Scholar 

  56. 56.

    Apel, W., Stark, D., Stark, A., O’Hagan, S., & Ling, J. (2013). Cobalt-chromium toxic retinopathy case study. Documenta Ophthalmologica, 126, 69–78.

    Article  PubMed  Google Scholar 

  57. 57.

    Manifold, I. H., Platts, M. M., & Kennedy, A. (1978). Cobalt cardiomyopathy in a patient on maintenance haemodialysis. British Medical Journal, 2, 1609.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. 58.

    Kennedy, A., Dornan, J. D., & King, R. (1981). Fatal myocardial disease associated with industrial exposure to cobalt. Lancet, 317, 412–414.

    Article  Google Scholar 

  59. 59.

    Jarvis, J. Q., Hammond, E., Meier, R., & Robinson, C. (1992). Cobalt cardiomyopathy: A report of two cases from mineral assay laboratories and a review of the literature. Journal of Occupational and Environmental Medicine, 34, 620–626.

    CAS  Google Scholar 

  60. 60.

    Balazs, T., & Herman, E. H. (1976). Toxic cardiomyopathies. Annals of Clinical and Laboratory Science, 6, 467–476.

    PubMed  CAS  Google Scholar 

  61. 61.

    Alexander, C. S. (1972). Cobalt-beer cardiomyopathy: A clinical and pathologic study of twenty-eight cases. American Journal of Medicine, 53, 395–417.

    Article  PubMed  CAS  Google Scholar 

  62. 62.

    Seghizzi, P., D’Adda, F., Borleri, D., Barbic, F., & Mosconi, G. (1994). Cobalt myocardiopathy: A critical review of literature. Science of the Total Environment, 150, 105–109.

    Article  PubMed  CAS  Google Scholar 

  63. 63.

    McDermott, P. H., Delaney, R. L., Egan, J. D., & Sullivan, J. F. (1966). Myocardosis and cardiac failure in men. The Journal of the American Medical Association, 198, 253–256.

    Article  PubMed  CAS  Google Scholar 

  64. 64.

    Regan, T. J., Lyons, M. M., Ahmed, S. S., Levinson, G. E., Oldewurtel, H. A., Ahmad, M. R., et al. (1977). Evidence for cardiomyopathy in familial diabetes mellitus. Journal of Clinical Investigation, 60, 884–899.

    Article  PubMed  CAS  Google Scholar 

  65. 65.

    Bell, D. S. (2003). Diabetic cardiomyopathy. Diabetes Care, 26, 2949–2951.

    Article  PubMed  Google Scholar 

  66. 66.

    Timoh, T., Bloom, M. E., Siegel, R. R., Wagman, G., Lanier, G. M., & Vittorio, T. J. (2012). A perspective on obesity cardiomyopathy. Obesity Research and Clinical Practice, 6, e175–e262.

    Article  PubMed  Google Scholar 

  67. 67.

    Amad, K. H., Brennan, J. C., & Alexander, J. K. (1965). The cardiac pathology of chronic exogenous obesity. Circulation, 32, 740–745.

    Article  PubMed  CAS  Google Scholar 

  68. 68.

    Factor, S. M., Minase, T., & Sonnenblick, E. H. (1980). Clinical and morphological features of human hypertensive-diabetic cardiomyopathy. American Heart Journal, 99, 446–458.

    Article  PubMed  CAS  Google Scholar 

  69. 69.

    Hamby, R. I., Zoneraich, S., & Sherman, L. (1974). Diabetic cardiomyopathy. JAMA, 229, 1749–1754.

    Article  PubMed  CAS  Google Scholar 

  70. 70.

    Alexander, J. K. (1985). The cardiomyopathy of obesity. Progress in Cardiovascular Diseases, 27, 325–334.

    Article  PubMed  CAS  Google Scholar 

  71. 71.

    Jardine, A. G., & McLaughlin, K. (2001). Cardiovascular complications of renal disease. Heart, 86, 459–466.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. 72.

    Mark, P. B., Johnston, N., Groenning, B. A., Foster, J. E., Blyth, K. G., Martin, T. N., et al. (2006). Redefinition of uremic cardiomyopathy by contrast-enhanced cardiac magnetic resonance imaging. Kidney International, 69, 1839–1845.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Michael Kovochich.

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All of the authors (EF, AM, MK, KU, BT, DG, BF, and DP) are or were employed by Cardno ChemRisk, a consulting firm that provides scientific advice to the government, corporations, law firms, and various scientific/professional organizations. Cardno ChemRisk has been engaged by DePuy Orthopaedics, Inc., a manufacturer of prosthetic devices, some of which contain cobalt and chromium, to provide general consulting and expert advice on scientific matters, as well as litigation support. Funding for the preparation of this paper was provided by DePuy. This work was supported by DePuy and they agreed, at the time of funding, that the findings would be published irrespective of the results. This paper was prepared and written exclusively by the authors, without review, or comment by DePuy employees or counsel. This work may be relied upon in medical research and litigation. One of the authors (DJP) has previously testified on behalf of DePuy in hip implant litigation. It is possible that any or all of the authors may be called upon to serve as expert witnesses on behalf of DePuy. The preparation of the paper, including conduct of the literature review, review of the individual papers, integration and synthesis of the findings, the conclusions drawn, and recommendations made are the exclusive professional work product of the authors, and may not necessarily be those of their employer or the financial sponsor of the review.

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Fung, E.S., Monnot, A., Kovochich, M. et al. Characteristics of Cobalt-Related Cardiomyopathy in Metal Hip Implant Patients: An Evaluation of 15 Published Reports. Cardiovasc Toxicol 18, 206–220 (2018). https://doi.org/10.1007/s12012-017-9433-z

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Keywords

  • Cobalt
  • Cardiomyopathy
  • Metal-on-polyethylene
  • Metal-on-metal
  • Hip implant