Algorithms for Management of Heart Transplant Rejection Based on Surveillance of Myocardial Damage by Antimyosin Antibody Imaging

  • Manel Ballester
  • Ignasi Carrió
  • Jagat Narula


Endomyocardial biopsy remains the only reliable diagnostic tool to detect acute allograft rejection (see Chapters 9,13)1–2. Biopsies are performed serially after transplantation, especially during the initial months. Immunosuppressive treatment is augmented when myocyte damage is detected by biopsy. Biopsy-based patient management is widely used and has been associated with very good long-term survival.3 However, there are significant limitations of endomyocardial biopsy. These include high procedural cost, a small but definite morbidity, and dwindling yield in obtaining adequate myocardial samples after the first year of transplantation. In addition, sampling error of the biopsy to detect acute rejection remains a major problem since myocardial expression of acute rejection is not a diffuse but rather a patchy. Rarely, patients who die of acute rejection demonstrate foci of myocardial damage and inflammation which can be seen surrounded by large areas of apparently intact myocardium.4,5


Acute Rejection Myocardial Damage Endomyocardial Biopsy Cardiac Allograft Rejection Myocyte Damage 
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  1. 1.
    Billingham ME, Cary NRB, Hammond ME, Kemnitz J, Marboe C, McCallister HA, Snovar DC, Winters GL, Zerbe A. A working formulation for the standardization of nomenclature in the diagnosis of heart and lng rejection: heart rejection study group. J Heart Transplant 1990;9:587–593.PubMedGoogle Scholar
  2. 2.
    Billingham ME. Can histopathology guide immunosuppression for cardiac allograft rejection in the light of new techniques? Transplant Proc 1997;29:35S–36S.PubMedCrossRefGoogle Scholar
  3. 3.
    Hosenpud JD, Bennett LE, Keck B, Boucek MM, Novick R. The Registry of the International Society for heart and lung transplantation. Sixeteenth official report 2000. J Heart Lung Transplant 2000;19:909–931.PubMedCrossRefGoogle Scholar
  4. 4.
    Goswitz JJ, Braunlin E, Kubo SH, Bolman EM III, Nakhleh RE. Pathology of heart transplantation: study of autopsied and explanted allografts with emphasis on possible biopsy findings. Clin Transplant 1992;6:450–457.Google Scholar
  5. 5.
    Billingham ME. Is acute cardiac rejection a model of myocarditis in humans?. Eur Heart J 1987;8 (Suppl):19–23.CrossRefGoogle Scholar
  6. 6.
    Khaw BA, Scott J, Fallon JT, Cahill SL, Haber E, Homey C. Myocardial injury: quantitation by cell sorting initiated with antimyosin fluorescent spheres. Science 1982;217:1050–1053.PubMedCrossRefGoogle Scholar
  7. 7.
    Khaw BA, Mattis JA, Melincoff G, Strauss HW, Gold HK, Haber E. Monoclonal antibody to cardiac myosin: imaging of experimental myocardial infarction. Hybridoma 1984;3:11–23.PubMedCrossRefGoogle Scholar
  8. 8.
    Obrador D, Ballester M, Carrió I, Bernà L, Pons G. High prevalence of ongoing myocyte damage in patients with chronic dilated cardiomyopathy. J Am Coll Cardiol 1989;13:1289–1293.PubMedCrossRefGoogle Scholar
  9. 9.
    Obrador D, Ballester M, Carrió I, Augè JM, Moya C, Bosch I, Martí V, Bordes R. Active myocardial damage without attending inflammatory response in idiopathic dilated cardiomyopathy. J Am Coll Cardiol 1993;21:1667–1671.PubMedCrossRefGoogle Scholar
  10. 10.
    Narula J, Khaw BA, Dec GW Jr, Palacios IF, Fallon JT, Strauss HW, Haber E, Yasuda T. Recognition of acute myocarditis masquerading as acute myocardial infarction. New Engl J Med 1992;328: 100–104.CrossRefGoogle Scholar
  11. 11.
    Obrador D, Ballester M, Carrió I, Moya C, Bosch I, Martí V, Bernà L, Estorch M, Udina U, Marrugat J, Augè JM, Carreras F, Pons-Lladó G, Caralps JM. Presence, evolving changes, and prognostic implications of myocardial damage detected in idiopathic and alcoholic dilated cardiomyopathy by 111-In monoclonal antimyosin antibodies. Circulation 1994;89:2054–2061.PubMedCrossRefGoogle Scholar
  12. 12.
    Narula J, Southern JF, Dec GW, Palacios IF, Newell JB, Fallon JT, Strauss HW, Khaw BA, Yasuda T. Myofibrillarlysis, antimyosin uptake and dilated cardiomyopathy. J Nucl Cardiol 1995;2:470–477.PubMedCrossRefGoogle Scholar
  13. 13.
    Martí V, Ballester M, Udina C, et al. Evaluation of active myocardial damage in patients with major depression on long-term treatment with tricyclic antidepressant drugs. A prospective study with In-111 monoclonal antimyosin antibodies. Circulation 1995;91:1619–1623.PubMedCrossRefGoogle Scholar
  14. 14.
    Narula J, Khaw BA, Dec GW, Newell JB, Palacios IF, Southern JF, Fallon JT, Strauss HW, Haber E, Yasuda T. Evaluation of diagnostic accuracy of antimyosin scintigraphy for the detection of myocarditis. J Nucl Cardiol 1996;3:471–481.Google Scholar
  15. 15.
    Frist W, Yasuda T, Segall G, Khaw BA, Strauss HW, Gold H, Stinson E, Oyer P, Baldwin J, Billingham M, McDougall R, Haber E. Noninvasive detection of human cardiac transplant rejection with In-111 antimyosin (Fab) imaging. Circulation 1987;76 (suppl V):81–85.Google Scholar
  16. 16.
    Ballester M, Carrió I, Abadal ML, Obrador D, Bernà L, Caralps-Riera JM. Patterns of evolution of myocyte damage after human heart transplantation detected by 111 Indium monoclonal antimyosin. Am J Cardiol 1988;62 (9):623–627.CrossRefGoogle Scholar
  17. 17.
    De Nardo D, Scibilia G, Macchiarelli AG, Cassisi A, Tonelli E, Papalia U, Gallo P, Antolini M, Pitucco G, Reale A, Caputo V, Marino B. The role of Indium-111 antimyosin (Fab) imaging as a noninvasive surveillance method of human heart transplant rejection. J Heart Transplant 1989;8:407–412.PubMedGoogle Scholar
  18. 18.
    Ballester M, Obrador D, Carrió I, Augé JM, Moya C, Pons-Lladó G, Caralps-Riera JM. 111In-monoclonal antimyosin antibody studies after the first year of heart transplantation: identification of risk groups for developing rejection during long-term follow-up and clinical implications. Circulation 1990;82:2100–2108.PubMedCrossRefGoogle Scholar
  19. 19.
    Schutz A, Fritsh S, Kugler C, Anthuber M, Sudhoff F, Wenke K, Spes C, Angermann C, Gokel JM, Kemkes BM. Indium-111 monoclonal antimyosin for diagnosis of cardiac rejection. Transplant Proc 1990;2274:1464–1465.Google Scholar
  20. 20.
    Crespo MG, Pulpón LA, Dominguez P, Chamorro JL, Argueso MJ, Padras G, Garcia M, Segovia J, Figuera D. Detection of human cardiac transplant rejection with Indium-111 monoclonal antimyosin antibody imaging. Transplant Proc 1990;22/4:1463.PubMedGoogle Scholar
  21. 21.
    Ballester M, Obrador D, Carrió I, Moya C, Augè JM, Bordes R, Martí V, Bosch I, Bernà L, Estorch M, Pons G, Cámara ML, Padró JM, Arís A, Caralps JM. Early postoperative reduction of monoclonal antimyosin antibody uptake is associated with absent rejection-related complications after heart transplantation. Circulation 1992;85:61–68.PubMedCrossRefGoogle Scholar
  22. 22.
    Hesse B, Mortensen SA, Folke M, Brodersen AKS, Aldershvile J, Pettersson G. Ability of antimyosin scintigraphy monitoring to exclude acute rejection during the first year after heart transplantation. J Heart Lung Transplant 1995;14:23–31.PubMedGoogle Scholar
  23. 23.
    Hosenpud JD. Noninvasive diagnosis of cardiac allograft rejection. Another of many searches for the grail. Circulation 1992;85:368–371.PubMedCrossRefGoogle Scholar
  24. 24.
    Khaw BA, Gold HK, Leinbach RC, et al. Early imaging of experimental myocardial infarction by intracoronary administration of 131I-labeled anticardiac myosin (Fab’)2 fragments. Circulation 1978;58:1137–1142.PubMedCrossRefGoogle Scholar
  25. 25.
    Khaw BA, Yasuda T, Gold HK, et al. Myocardial imaging with radiolabeled antibodies. In: Spry CJF, de. Immunology and Molecular Biology of Cardiovascular Diseases. Lancaster, UK: MTP Press; 1987.Google Scholar
  26. 26.
    Nedelman MA, Shealy DJ, Boulin R, et al. Rapid infarct imaging with a technetium-99m-labeled antimyosin recombinant single chain Fv: evaluation in a canine model of acute myocardial infarction. J Nucl Med 1993;34:234–241.PubMedGoogle Scholar
  27. 27.
    Khaw BA, Strauss HW, Pohost GM, et al. The relationship of immediate and delayed thallium-201 distribution to localization of I125-antimyosin antibody in acute experimental infarction. Am J Cardiol 1983;51:1428–1432.PubMedCrossRefGoogle Scholar
  28. 28.
    Rezcalla S, Kloner RA, Khaw BA, Haber E, Fallon JT, Smith FE, Khatib R. Detection of experimental myocarditis by monoclonal antimyosin antibody Fab fragments. Am Heart J 1989;117:391–395.CrossRefGoogle Scholar
  29. 29.
    Kishimoto C, Hung GL, Ishibashi M, Khaw BA, Kolodny GM, et al. Natural evolution of cardiac functions, cardiac pathology, and antimyosin scans in a murine myocarditis model. J Am Coll Cardiol 1991;17:821–827.PubMedCrossRefGoogle Scholar
  30. 30.
    Matsumori A, Ohkusha T, Matoba Y, Okada I, Yasuda T, et al. Myocardial uptake of antimyosin monoclonal antibody in a murine model of viral myocarditis. Circulatin 1989;79:400–405.CrossRefGoogle Scholar
  31. 31.
    Khaw BA, Russell PS, Roseel J, Fergusson P, Haber E. New approach to determination of heart transplant rejection by I125-antimyosin antibody and Tc99m-fibrinogen. Clin Res 1981;29:496.Google Scholar
  32. 32.
    Khaw BA, Yasuda T, Palacios I, Fallon JT, Dec GW, et al. Diagnosis of acute myocarditis with radiolabeled monoclonal antimyosin antibody: Immunoscintigraphic evaluation. In Schultheiss ed. New concepts in viral disease. Springer Verlag 1988, pp. 363–373.CrossRefGoogle Scholar
  33. 33.
    Isobe M, Khaw BA, Haber E. Early detection of rejection and assessment of cyclosporine therapy by indium-111-antimyosin imaging in mouse heart allografts. Circulation 1991;84:1246–1255.PubMedCrossRefGoogle Scholar
  34. 34.
    Addonizio LJ, Michler RE, Marboe RE, Esser PE, Johnson LJ, et al. Imaging of cardiac allograft rejection in dogs using indium111-antimyosin Fab. J Am Coll Cardiol 1987;9:555–564.PubMedCrossRefGoogle Scholar
  35. 35.
    Sainani GS, Krompotic E, Slodki SJ. Adult heart disease due to coxsackie B virus infection. Medicine (Baltimore) 1968;47:133–147.CrossRefGoogle Scholar
  36. 36.
    Smith WG. Coxsackie B myopericarditis in adults. Am Heart J 1970;80:34–46.PubMedCrossRefGoogle Scholar
  37. 37.
    Lerner AM, Wilson FM, Reyes MP. Enteroviruses and the heart with special emphasis on the probable role of coxsackie B viruses. Epidemiological and experimental studies. Mod Concepts Cardiovasc Dis 1975;44:7–10.PubMedGoogle Scholar
  38. 38.
    Dec GW, Palacios IF, Yasuda T, Fallon JT, Khaw BA, et al. Antimyosin antibody cardiac imaging: its role in the diagnosis of myocarditis. J Am Coll Cardiol 1990;16:97–104.PubMedCrossRefGoogle Scholar
  39. 39.
    Narula J, Yasuda T, Khaw BA, Southern BA, Dec GW, et al. Antimyosin scintigraphy in detection of myocarditis: evaluation of a diagnostic methodology. J Am Coll Cardiol 1991;17:342.CrossRefGoogle Scholar
  40. 40.
    Narula J, Khaw BA, Dec GW, Palacios IF, Southern JF, Fallon JT, et al. Recognition of acute myocarditis masquerading as acute myocardial infarction. N Engl J Med 1993;328:100–104.PubMedCrossRefGoogle Scholar
  41. 41.
    Abelman WH, Roberts WC. Cardiomyopathy and specific heart muscle disease. In: Hurst JW ed. The Heart. New York: McGraw-Hill 1989:1313.Google Scholar
  42. 42.
    Casans I, Villar A, Almenar V, Blanes A. Lyme myocarditis diagnosed by indium-111 antimyosin scintigraphy. Eur J Nucl Med 1989;15:330–331.PubMedCrossRefGoogle Scholar
  43. 43.
    Malhotra A, Narula J, Yasuda T, Reddy KS, Chopra P, et al. In111-antimyosin antibody imaging for diagnosis of rheumatic carditis. J Nucl Med 1990;31:841.Google Scholar
  44. 44.
    Samuels MA, Southern JF. Case records of the Massachusetts General Hospital. N Engl J Med 1988;318:970–980.CrossRefGoogle Scholar
  45. 45.
    Estorch M, Carrió I, Berná L, et al. Indium-111 antimyosin scintigraphy after doxorubicin therapy in patients with advanced breast cancer. J Nucl Med 1990;12:1965–1970.Google Scholar
  46. 46.
    Carrió I, Estorch M, Berná L, et al. Assessment of anthracycline induced myocardial damage by quantitative indium-111 myosin specific monoclonal antibody studies. Eur J Nucl Med 1991;18:806–812.PubMedCrossRefGoogle Scholar
  47. 47.
    Carrió I, Lopez-Pousa L, Estorch M, et al. Detection of doxorubicin cardiotoxicity in patients with sarcomas by indium-111 antimyosin monoclonal antibody studies. J Nucl Med 1993;34:1503–1507.PubMedGoogle Scholar
  48. 48.
    Valdés-Olmos R, ten Bokkel-Huinink WW, ten Hoeve RF, et al. Usefulness of indium-111 antimyosin scintigraphy in confirming myocardial injury in patients with anthracycline associated left ventricular dysfunction. Ann Oncol 1994;5:617–627.PubMedGoogle Scholar
  49. 49.
    Carrió I, Berná LI, Ballester M, et al. Indium-111 antimyosin scintigraphy to assess myocardial damage in patients with suspected myocarditis and heart transplant rejection. J Nucl Med 1988;29:1893–1900.PubMedGoogle Scholar
  50. 50.
    Pous-Llado G, Ballester M, Borras X, Carreras F, Cavrio I, Lopez-Contreras J, Roca-Cusacks A, Najula J. Myocardial cell damage in human hypertension. J Am Coll Cardiol 2000;36:2198–2203.CrossRefGoogle Scholar
  51. 51.
    Ballester M, Obrador D, Carrió I, et al. Early post-operative reduction of monoclonal antimyosin antibody uptake is associated with absent rejection-related complications after heart transplantation. Circulation 1992;85:61–68.PubMedCrossRefGoogle Scholar
  52. 52.
    Carrió I, Estorch M, Berná LI, et al. Indium-111 antimyosin and iodine-123 MIBG studies in early assessment of doxorubicin cardiotoxicity. J Nucl Med 1995;36:2044–2049.PubMedGoogle Scholar
  53. 53.
    Obrador D, Ballester M, Carrió I, et al. Presence, evolving changes, and prognostic implications of myocardial damage detected in idiopathic and alcoholic dilated cardiomyopathy by indium-111 monoclonal antimyosin studies. Circulation 1994;89:2054–2061.PubMedCrossRefGoogle Scholar
  54. 54.
    Ballester M, Bordes R, Tazelaar H, Carrio I, Marugat J, Narrula J, Billingham ME. Evaluation of biopsy classification for rejection: relation to detection of myocardial damage by monoclonal antimyosin antibody imaging. J Am Coll Cardiol 1998;31:1357–1361.PubMedCrossRefGoogle Scholar
  55. 55.
    Obrador D, Bordes R, Cladellas M, Abadal ML, Ballester M, Augé JM. Detección de miocarditis mediante biopsia endomiocárdica en los candidatos a trasplante cardíaco. Rev Esp Cardiol 1987 (Supl. II);40:14–17.PubMedGoogle Scholar
  56. 56.
    Chow LH, Radio SJ, Sears TD, McManus BM. Insensivity of right ventricular biopsy in the diagnosis of myocarditis. J Am Coll Cardiol 1989;14:915–920.PubMedCrossRefGoogle Scholar
  57. 57.
    Hauck AJ, Kearney DL, Edwards WD. Evaluation of postmortem endomyocardial biopsy specimens from 38 patients with lymphocytic myocarditis: implications for the role of sampling error. Mayo ClinProc 1989;64:1235–1245.Google Scholar
  58. 58.
    Narula J, Haider N, Virmani R, DiSalvo TG, Kolodgie FD, Hajjar R, Schmidt U, Semigran MJ, Dec GW, Khaw BA. Apoptosis in end-stage heart failure. N Engl J Med 1996;335:1182–1189.PubMedCrossRefGoogle Scholar
  59. 59.
    Narula J, Kharbanda S, Khaw BA. Apoptosis cardiac diseases. Chest 1997;112:1358–1362.PubMedCrossRefGoogle Scholar
  60. 60.
    Narula J, Chandrashekhar Y, Dec GW. Apoptosis in heart failure: a tale of hightened expectations, unfulfilled promises and broken hearts … Apoptosis: 1998;3:309–315.PubMedCrossRefGoogle Scholar
  61. 61.
    Dec GW, Hajjar R, Narula J. Apoptosis in the failing heart. Cardiol Clin 1998;16:691–710.PubMedCrossRefGoogle Scholar
  62. 62.
    Puig M, Ballester M, Matias-Guiu X, Bordes R, Carrió I, Aymat MR, Marrugat J, Padró JM, Caralps JM, Narula J. Apoptosis of myocytes in cardiac allograft rejection: An addtional mechanism of myocardial damage away from foci of myocyte necrosis. J Nucl Cardiol 2000;7:132–139.PubMedCrossRefGoogle Scholar
  63. 63.
    Ballester M, Obrador D, Carrió I, Caralps-Riera JM. 111In-monoclonal antimyosin antibody studies in the diagnosis of rejection and management of patients after heart transplantation. In: Monoclonal Antibodies in Cardiovascular Disease. Khaw BA, Narula J, Strauss WH (Eds). Lea and Febiger. Philadelphia. 1994. pp. 79–98.Google Scholar
  64. 64.
    Lamich R, Ballester M, Marti V, Brossa V, Ayurat R, Carrio I, Berna L, Camprecios M, Puig M, Estorch M, Flotats A, Bordes R, Augé JM, Dadró JM, Caralps JM, Narula J. Efficacy of augmented immunosuppressive therapy for early vasculopathy in heart transplantation. J Am Coll Cardiol 1998;32:413–419.PubMedCrossRefGoogle Scholar
  65. 65.
    Bhattacharya S, Crawley JCW, Lahiri A. Specific binding of 99MTc-antimyosi to necrotic human myocardium: clinicopathologic correlations. Am Heart J 1991;122:857–859.PubMedCrossRefGoogle Scholar
  66. 66.
    Moya C, Ballester M, Bernà LI, Aymat MR, Carrió I, Altimiras J, Martí V, Tuneu L, Obrador D, Peña V, Lamich R, Padró JM, Bonal J, Narula J. Chronic low-dose steroid treatment helps in maintenance of long-term tolerance to the cardiac allografts. J Nucl Cardiol (in press).Google Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Manel Ballester
    • 1
  • Ignasi Carrió
    • 2
  • Jagat Narula
    • 3
  1. 1.Department of CardiologyLleida UniversityLleidaSpain
  2. 2.Department of Nuclear Medicine Hospital de Sant PauBarcelonaSpain
  3. 3.Heart Failure/Transplantation CenterHahnemann University HospitalPhiladelphiaUSA

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