Skip to main content

Advertisement

Log in

Non-invasive cardiac allograft rejection surveillance: reliability and clinical value for prevention of heart failure

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

Allograft rejection-related acute and chronic heart failure (HF) is a major cause of death in heart transplant recipients. Given the deleterious impact of late recognized acute rejection (AR) or non-recognized asymptomatic antibody-mediated rejection on short- and long-term allograft function improvement of AR surveillance and optimization of action strategies for confirmed AR can prevent AR-related allograft failure and delay the development of cardiac allograft vasculopathy, which is the major cause for HF after the first posttransplant year. Routine non-invasive monitoring of cardiac function can improve both detection and functional severity grading of AR. It can also be helpful in guiding the anti-AR therapy and timing of routine surveillance endomyocardial biopsies (EMBs). The combined use of EMBs with non-invasive technologies and methods, which allow detection of subclinical alterations in myocardial function (e.g., tissue Doppler imaging and speckle-tracking echocardiography), reveal alloimmune activation (e.g., screening of complement-activating donor-specific antibodies and circulating donor-derived cell-free DNA) and help in predicting the imminent risk of immune-mediated injury (e.g., gene expression profiling, screening of non-HLA antibodies, and circulating donor-derived cell-free DNA), can ensure the best possible surveillance and management of AR. This article gives an overview of the current knowledge about the reliability and clinical value of non-invasive cardiac allograft AR surveillance. Particular attention is focused on the potential usefulness of non-invasive tools and techniques for detection and functional grading of early and late ARs in asymptomatic patients. Overall, the review aimed to provide a theoretical and practical basis for those engaged in this particularly demanding up-to-date topic.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Yilmaz A, Kindermann I, Kindermann M, Mahfoud F, Ukena C, Athanasiadis A, Hill S, Mahrholdt H, Voehringer M, Schieber M, Klingel K, Kandolf R, Böhm M, Sechtem U (2010) Comparative evaluation of left and right ventricular endomyocardial biopsy: differences in complication rate and diagnostic performance. Circulation 122(9):900–909

    PubMed  Google Scholar 

  2. Baraldi-Junkins C, Levin HR, Kasper EK et al (1993) Complications of endomyocardial biopsy in heart transplant patients. J Heart Lung Transplant. 12(1 Pt 1):63–67

    PubMed  CAS  Google Scholar 

  3. Miller CA, Fildes JE, Ray SG, Doran H, Yonan N, Williams SG, Schmitt M (2013) Non-invasive approaches for diagnosis of acute cardiac allograft rejection. Heart 99:445–453

    PubMed  CAS  Google Scholar 

  4. Dandel M, Kemper D, Lehmkuhl H et al (2004) Acute rejections during late posttransplant periods in pediatric heart transplant recipients. J Am Coll Cardiol 43(Suppl A):193–194

    Google Scholar 

  5. Subherwal S, Kobashigawa JA, Cogert G et al (2004) Incidence of acute cellular rejection and non-cellular rejection in cardiac transplantation. Transplant Proc 6(10):3171–3172

    Google Scholar 

  6. Eckart RE, Kolasa MW, Khan NA et al (2005) Rejection and ECG changes in OHT. Ann Noninvasive Electrocardiol 10(1):60–64

    PubMed  PubMed Central  Google Scholar 

  7. Lacroix D, Kacet S, Savard P, Molin F, Dagano J, Pol A, Lekieffre J (1992) Signal-averaged electrocardiography and detection of heart transplant rejection: comparison of time and frequency domain analyses. J Am Coll Cardiol 19(3):553–558

    PubMed  CAS  Google Scholar 

  8. Horenstein MS, Idriss SF, Hamilton RM et al (2006) Efficacy of signal-averaged electrocardio-graphy in the young orthotopic heart transplant patient to detect allograft rejection. Pediatr Cardiol 27(5):589–593

    PubMed  CAS  Google Scholar 

  9. Hickey KT, Sciacca RR, Chen B, Drew BJ, Pickham D, Carter EV, Castillo C, Doering LV (2018) Electrocardiographic correlates of acute allograft rejection among heart transplant recipients. Am J Crit Care 27(2):145–150

    PubMed  Google Scholar 

  10. Warnecke H, Schüler S, Goetze HJ et al (1986) Noninvasive monitoring of cardiac allograft rejection by intramyocardial electrogram recordings. Circulation 74(5 Pt2):III72–III76

    PubMed  CAS  Google Scholar 

  11. Hetzer R, Potapov EV, Müller J, Loebe M, Hummel M, Weng Y, Warnecke H, Lange PE (1998) Daily noninvasive rejection monitoring improves long-term survival in pediatric heart transplantation. Ann Thorac Surg 66(4):1343–1349

    PubMed  CAS  Google Scholar 

  12. Warnecke H, Müller J, Cohnert T et al (1992) Clinical heart transplantation without routine endomyocardial biopsy. J Heart Lung Transplant 11(6):1093–1102

    PubMed  CAS  Google Scholar 

  13. Müller J, Eubel A, Dandel M, Hummel M, Hetzer R (2001) Non-invasive monitoring of rejection after cardiac transplantation. The method and retrospective analysis of data on 734 patients. Dtsch Med Wochenschr. 126(44):1223–1228

    PubMed  Google Scholar 

  14. Hummel M, Dandel M, Knollmann F, Müller J, Knosalla C, Ewert R, Grauhan O, Meyer R, Hetzer R (2001) Long-term surveillance of heart-transplanted patients: noninvasive monitoring of acute rejection episodes and transplant vasculopathy. Transplant Proc 33(7-8):3539–3542

    PubMed  CAS  Google Scholar 

  15. Hummel M, Dandel M, Müller J, Hetzer R (2002) Surveillance biopsies in heart and lung transplantation. Transplant Proc 34(5):1860–1863

    PubMed  CAS  Google Scholar 

  16. Eisen HJ (1999) Noninvasive detection of cardiac transplant rejection using electronic monitoring. Curr Opin Cardiol 4(2):151–154

    Google Scholar 

  17. Grasser G, Iberer F, Schreier G et al (2003) Computerized heart allograft-recipient monitoring: a multicenter study. Transpl Int. 16(4):225–230

    PubMed  Google Scholar 

  18. Bourge R, Eisen H, Hershberger R et al (1998) Transplants using high resolution intramyocardial electrograms: initial US multicenter experience. Pacing Clin Electrophysiol 21(11 Pt2):2338–2344

    PubMed  CAS  Google Scholar 

  19. Dandel M, Hummel M, Müller J et al (2001) Reliability of tissue Doppler wall motion monitoring after heart transplantation for replacement of invasive routine screenings by optimally timed cardiac biopsies and catheterizations. Circulation;104[suppl I]:I-184-I-191

  20. Dandel M, Hetzer R (2017) Post-transplant surveillance for acute rejection and allograft vasculopathy by echocardiography: usefulness of myocardial velocity and deformation imaging. J Heart Lung Transplant. 36(2):117–131

    PubMed  Google Scholar 

  21. Ciliberto GR, Cataldo G, Cabrol A et al (1989) Echocardiographic assessment of cardiac allograft rejection. Eur Heart J 10:400–408

    PubMed  CAS  Google Scholar 

  22. Desruennes M, Corcos T, Cabrol A, Gandjbakhch I, Pavie A, Léger P, Eugène M, Bors V, Cabrol C (1988) Doppler echocardiography for the diagnosis of acute cardiac allograft rejection. J Am Coll Cardiol 12(1):63–70

    PubMed  CAS  Google Scholar 

  23. Boyd SY, Mego DM, Khan NA et al (1997) Doppler echocardiography in cardiac transplant patients: allograft rejection and its relationship to diastolic function. J Am Soc Echocardiogr. 10(5):526–531

    PubMed  CAS  Google Scholar 

  24. Dodd DA, Brady LD, Carden KA, Frist WH, Boucek MM, Boucek RJ Jr (1993) Pattern of echocardiographic abnormalities with acute cardiac allograft rejection in adults: correlation with endomyocardial biopsy. J Heart Lung Transplant 12(6 Pt 1):1009–1018

    PubMed  CAS  Google Scholar 

  25. Wu HA, Kolias TJ (2012) Cardiac transplantation: pretransplant and posttransplant evaluation. In Otto CM ed. The Practice of Clinical Echocardiography, 4th Edition, 585-596

  26. Fauchier L, Sirunelli A, Aupart M et al (1997) Echocardiographic Doppler study of left ventri-cular filling in the diagnosis of minimal or moderate rejection in cardiac transplantation. Arch Mal Coeur Vaiss 90(12):1623–1628

    PubMed  CAS  Google Scholar 

  27. Lu W, Zheng J, Pan X, Sun L (2015) Diagnostic performance of echocardiography for the detection of acute cardiac allograft rejection: a systematic review and meta-analysis. PLoS ONE 10(3):e0121228. https://doi.org/10.1371/journal.pone.0121228

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Dandel M, Kemper D, Lehmkuhl H, Hetzer R (2004) Evaluation of left ventricular filling pressures by the Tei index. J Am Soc Echocardiogr 17(6):709

    PubMed  Google Scholar 

  29. Dandel M, Wellnhofer E, Hummel M, Meyer R, Lehmkuhl H, Hetzer R (2003) Early detection of left ventricular dysfunction related to transplant coronary artery disease. J Heart Lung Transplant. 22:1353–1364

    PubMed  Google Scholar 

  30. Masuyama T, Valantine HA, Gibbons R, Schnittger I, Popp RL (1990) Serial measurement of integrated backscatter in human cardiac allografts for recognition of acute rejection. Circulation 81:829–839

    PubMed  CAS  Google Scholar 

  31. Lieback E, Meyer R, Nawrocki M et al (1994) Noninvasive diagnosis of cardiac rejection through echocardiographic tissue characterization. Ann Thorac Surg 57:1164–1170

    PubMed  CAS  Google Scholar 

  32. Angermann CE, Nassau K, Stempfle HU, Kru¨ger TM, Drewello R, Junge R, U¨berfuhr P, Weiß M, Theisen K (1997) Recognition of acute cardiac allograft rejection from serial integrated backscatter analyses in human orthotopic heart transplant recipients. Circulation 95(1):140–150

    PubMed  CAS  Google Scholar 

  33. Badano LP, Miglioranza MH, Edwardsen T et al (2015) European Association of Cardiovascular Imaging / Cardiovascular Imaging Department of the Brasilian Society of Cardiology recommendations for the use of cardiac imaging to assess and follow patients after heart transplantation. Eur Heart J – Cardiovascular Imaging 16:919–948

    Google Scholar 

  34. Derumeaux G, Douillet R, Redonnet M (1998) Detection of acute rejection of heart transplantation by Doppler color imaging. Arch Mal Coeur Vaiss 91:1255–1262

    PubMed  CAS  Google Scholar 

  35. Puleo JA, Aranda JM, Weston MW, Cintrón G, French M, Clark L, Fontanet HL (1998) Noninvasive detection of allograft rejection in heart transplant recipients by use of Doppler tissue imaging. J Heart Lung Transplant 17:176–184

    PubMed  CAS  Google Scholar 

  36. Mankad S, Murali S, Kormos RL, Mandarino WA, Gorcsan J III (1999) Evaluation potential role of color-coded tissue Doppler echocardiography in the detection of allograft rejection in heart transplant recipients. Am Heart J 138(4 Pt 1):721–730

    PubMed  CAS  Google Scholar 

  37. Lunze FI, Colan SD, Gauvreau K et al (2013) Tissue Doppler imaging for rejection surveillance in pediatric heart transplant recipients. J Heart Lung Transplant 32:1027–1033

    PubMed  Google Scholar 

  38. Resende MVC, Vieira MLC, Bacal F, Andrade JL, Stolf NA, Bocchi EA (2011) Tissue Doppler echocardiography in the diagnosis of heart transplantation rejection. Arq Bras Cardiol 97(1):8–16

    PubMed  Google Scholar 

  39. Fabregas RI, Crespo-Leiro MG, Regueiro M et al (1999) Usefulness of pulse Doppler tissue imaging for non-invasive detection of cardiac rejection after heart transplantation. Transplant Proc 31(6):2545–2547

    PubMed  CAS  Google Scholar 

  40. Pauluks LB, Pietra BA, DeGroff CG et al (2005) Non-invasive detection of acute allograft rejection in children by tissue Doppler imaging: myocardial velocities and myocardial acceleration during isovolumic contraction. J Heart Lung Transplant 24(7 Suppl):S239–S248

    Google Scholar 

  41. Edvardsen T, Gerber BL, Garot J et al (2002) Quantitative assessment of intrinsic regional myocar-dial deformation by Doppler strain rate echocardiography in humans. Circulation 106(1):50–56

    PubMed  Google Scholar 

  42. Eun LY, Gajarski RJ, Graziano JN et al (2005) Relation of left ventricular diastolic function as measured by echocardiography and pulmonary wedge pressure to rejection in young (≤ 30 years) patients. Am J Cardiol 96(6):857.60

    PubMed  Google Scholar 

  43. Palka P, Lange A, Galbraith A, Duhig E, Clarke BE, Parsonage W, Donnelly JE, Stafford WJ, Burstow DJ (2005) The role of left and right ventricular early diastolic Doppler tissue echocardiographic indices in evaluation of acute rejection in orthotopic heart transplant. J Am Soc Echocardiogr 18:107–115

    PubMed  Google Scholar 

  44. Bader FM, Islam N, Mehta NA, Worthen N, Ishihara S, Stehlik J, Gilbert EM, Litwin SE (2011) Noninvasive diagnose of cardiac allograft rejection using echocardiography indices of systolic and diastolic function. Transplant Proc 43(10):3877–3881

    PubMed  CAS  Google Scholar 

  45. Stengel SM, Allemann Y, Zimmerly M et al (2001) Doppler tissue imaging for assessing left ventricular diastolic dysfunction in heart transplant rejection. Heart 86:432–437

    PubMed  PubMed Central  CAS  Google Scholar 

  46. Sun JP, Abdalla IA, Asher CR, Greenberg NL, Popović ZB, Taylor DO, Starling RC, Thomas JD, Garcia MJ (2005) Non-invasive evaluation of heart transplant rejection by echocardiography. J Heart Lung Transplant 24(2):160–165

    PubMed  Google Scholar 

  47. Dandel M, Hetzer R (2018) Evaluation of the right ventricle by echocardiography: particularities and major challenges. Expert Reviews of Cardiovascular Therapy 16(4):259–275

    PubMed  CAS  Google Scholar 

  48. Dandel M, Hummel M, Meyer R, Müller J, Kapell S, Ewert R, Hetzer R (2002) Left ventricular dysfunction during cardiac allograft rejection: early diagnosis, relationship to the histological severity grade and therapeutic implications. Transpl Proc 34:2169–2173

    CAS  Google Scholar 

  49. Clemmensen TS, Løgstrup BB, Eiskjaer H et al (2015) The long-term influence of repetitive cellular cardiac rejections on left ventricular longitudinal myocardial deformation in heart transplant recipients. Transpl Int 8(4):475–484

    Google Scholar 

  50. Tang ZY, Kobashigawa J, Rafiei M et al (2013) The natural history of biopsy-negative rejection after heart transplantation. J Heart Lung Transplant 32(7):744–746

    Google Scholar 

  51. Yamada H, Oki T, Tabata T, Iuchi A, Ito S (1998) Assessment of left ventricular systolic wall motion velocity with pulsed tissue Doppler imaging: comparison with peak dP/dt of left ventricular pressure curve. J Am Soc Echocardiogr 11:442–449

    PubMed  CAS  Google Scholar 

  52. Dandel M, Hetzer R (2009) Echocardiographic strain and strain rate imaging – clinical applications. Int J Cardiol 132:11–24

    PubMed  Google Scholar 

  53. Gorcsan J 3rd, Tahaka H (2011) Echocardiographic assessment of myocardial strain. J Am Coll Cardiol. 58(14):1401–1413

    PubMed  Google Scholar 

  54. Dandel M, Lehmkuhl H, Knosalla C, Hetzer R (2007) Non-Doper two-dimensional strain imaging - clinical applications. J Am Soc Echocardiogr 20(8):1019

    PubMed  Google Scholar 

  55. Marciniak A, Eroglu E, Marciniak M et al (2007) The potential clinical role of ultrasonic strain and strain rate imaging in diagnosing acute rejection after heart transplantation. Eur J Echocardiogr 8:213–221

    PubMed  Google Scholar 

  56. Kato TS, Oda N, Hashimura K, Hashimoto S, Nakatani T, Ueda HI, Shishido T, Komamura K (2010) Strain rate imaging would predict subclinical acute rejection in heart transplant recipients. Eur J Cardiothorac Surg 37:1104–1110

    PubMed  Google Scholar 

  57. Sato T, Kato TS, Komamura K et al (2011) Utility of left ventricular systolic torsion derived from 2-dimensional speckle-tracking echocardiography in monitoring acute cellular rejection in heart transplant recipients. J Heart Lung Transplant 30(5):536–543

    PubMed  Google Scholar 

  58. Sera F, Kato TS, Farr M, Russo C, Jin Z, Marboe CC, di Tullio MR, Mancini D, Homma S (2014) Left ventricular longitudinal strain by speckle-tracking echocardiography is associated with treatment-requiring cardiac allograft rejection. J Card Fail 20(5):359–364

    PubMed  Google Scholar 

  59. Mingo-Santos S, Moňivas-Palomero V, Garcia-Lunar I et al (2015) Usefulness of two-dimensional strain parameters to diagnose acute rejection after heart transplantation. Am Soc Echocardiogr 28:1149–1156

    Google Scholar 

  60. Sehgal S, Blake JM, Sommerfield J, Aggarwal S (2015) Strain and strain rate imaging using speckle tracking in acute allograft rejection in children with heart transplantation. Pediatr Transplantation 19:188–195

    Google Scholar 

  61. Pieper GM, Shah A, Harmann L, Cooley BC, Ionova IA, Migrino RQ (2010) Speckle-tracking echocardiography: a new non-invasive tool to evaluate acute rejection in cardiac transplantation. J Heart Lung Transplant 29(9):1039–1046

    PubMed  PubMed Central  Google Scholar 

  62. Dandel M, Lehmkuhl H, Siniawski H et al (2010) Discordance between morphological and functional alterations during cardiac allograft rejection: diagnostic value of myocardial wall motion and deformation imaging. J Heart Lung Transplant 29(2):S154–S155

    Google Scholar 

  63. Ruiz Ortiz M, Peña ML, Mesa D, Delgado M, Romo E, Santisteban M, Puentes M, López Granados A, Castillo JC, Arizón JM, de Lezo JS (2015) Impact of asymptomatic acute cellular rejection on left ventricle myocardial function evaluated by means of two-dimensional speckle tracking echocardiography in heart transplant recipients. Echocardiography 32:229–237

    PubMed  Google Scholar 

  64. Ambardekar AV, Alluri N, Patel AC, Lindenfeld JA, Dorosz JL (2015) Myocardial strain and strain rate from speckle-tracking echocardiography are unable to differentiate asymptomatic biopsy-proven cellular rejection in the first year after cardiac transplantation. J Am Soc Echocardiogr 28(4):478–485

    PubMed  Google Scholar 

  65. Clemmensen ST, Løgstrup BB, Eiskjǽr H, Poulsen H (2015) Changes in longitudinal myocardial deformation during acute cardiac rejection: the clinical role of two-dimensional speckle-tracking Echocardiography. J Am Soc Echocardiogr 28:330–339

    PubMed  Google Scholar 

  66. Zhu S, Li M, Tian F et al (2020) Diagnostic value of myocardial strain using two-dimensional speckle-tracking echocardiography in acute cardiac allograft rejection: a systematic review and meta-analysis. Echocardiography. 22. https://doi.org/10.1111/echo.14637 Online ahead of print

  67. Elkaryoni A, Altibi AM, Khan SM et al (2020) Global longitudinal strain assessment of the left ventricle by speckle tracking echocardiography detects acute cellular rejection in orthotopic heart trans-plant recipients: a systematic review and meta-analysis. Echocardiography 37(2):302–309

    PubMed  Google Scholar 

  68. Shi J, Pan C, Shu X, Sun M, Yang Z, Zhu S, Wang C (2011) The role of speckle tracking imaging in the non-invasive detection of acute rejection after heterotopic cardiac transplantation in rats. Acta Cardiol 66:779–785

    PubMed  Google Scholar 

  69. Du GQ, Hsiung MC, Wu Y et al (2016) Three-dimensional speckle-tracking echocardiographic monitoring of acute rejection in heart transplant recipients. J Ultrasound Med. 35(6):1167–1176

    PubMed  Google Scholar 

  70. Estep JD, Shah DJ, Naguch S (2009) The role of multimodality cardiac imaging in the transplanted heart. JACC Cardiovasc Imaging. 2:1126–1140

    PubMed  Google Scholar 

  71. Sade LE, Hazirolan T, Kozan H et al (2019) T1 Mapping by cardiac magnetic resonance and multi-dimensional speckle-tracking strain by echocardiography for the detection of acute cellular rejection in cardiac allograft recipients. JACC Cardiovasc Imaging. 12(8 Pt 2):1601–1614

    PubMed  Google Scholar 

  72. Dolan RS, Rahsepar AA, Blaisdell J et al (2019) Multiparametric cardiac magnetic resonance imaging can detect acute cardiac allograft rejection after heart transplantation. JACC Cardiovasc Imaging

  73. Marie PY, Angioї M, Carteaux JP (2001) Detection and prediction of acute heart transplant rejection with the myocardial T2 determination provided by a black-blood magnetic resonance imaging sequence. JACC 37(3):825–831

    PubMed  CAS  Google Scholar 

  74. Butler CR, Savu A, Bakal JA, Toma M, Thompson R, Chow K, Wang H, Kim DH, Mengel M, Haykowsky M, Pearson GJ, Kaul P, Paterson I (2015) Correlation of cardiovascular magnetic resonance imaging findings and endomyocardial biopsy results in patients undergoing screening for heart transplant rejection. J Heart Lung Transplant. 34(5):643–650

    PubMed  Google Scholar 

  75. Krieghoff C, Barten MJ, Hildebrand L, Grothoff M, Lehmkuhl L, Lücke C, Andres C, Nitzsche S, Riese F, Strüber M, Mohr FW, Gutberlet M (2014) Assessment of subclinical acute cellular rejection after heart transplantation: comparison of cardiac magnetic resonance imaging and endomyocardial biopsy. Eur Radiol. 24(10):2360–2371

    PubMed  PubMed Central  Google Scholar 

  76. Taylor AJ, Vaddadi G, Pfluger H, Butler M, Bergin P, Leet A, Richardson M, Cherayath J, Iles L, Kaye DM (2010) Diagnostic performance of multisequential cardiac magnetic resonance imaging in acute cardiac allograft rejection. Eur J Heart Fail 12(1):45–51

    PubMed  PubMed Central  Google Scholar 

  77. Chen Y, Zhang L, Jinfeng LJ et al (2017) Molecular imaging of acute cardiac transplant rejection: animal experiments and prospects. Transplantation. 101(9):1977–1986

    PubMed  PubMed Central  Google Scholar 

  78. Wu YL, Ye Q, Eytan DF, Liu L, Rosario BL, Hitchens TK, Yeh FC, Rooijen van N, Ho C (2013) Magnetic resonance imaging investigation of macrophages in acute cardiac allograft rejection after heart transplantation. Circ Cardiovasc Imaging. 6(6):965–973

    PubMed  Google Scholar 

  79. Hitchens TK, Ye Q, Eytan DF, Janjic JM, Ahrens ET, Ho C (2011) 19F MRI detection of acute allograft rejection with in vivo perfluorocarbon labeling of immune cells. Magn Reson Med. 65(4):1144–1153

    PubMed  PubMed Central  Google Scholar 

  80. Meneguetti JC, Camargo EE, Soares J Jr et al (1987) Gallium-67 imaging in human heart transplantation: correlation with endomyocardial biopsy. J Heart Transplant 6(3):171–176

    PubMed  CAS  Google Scholar 

  81. De Nardo D, Scibilia G, Macchiarelli AG et al (1989) The role of indium-111 antimyosin (Fab) imaging as a noninvasive surveillance method of human heart transplant rejection. J Heart Transplant 8(5):407–412

    PubMed  Google Scholar 

  82. Kobashigawa J, Colvin M, Potena L et al (2018) The management of antibodies in heart trans-plantation: an ISHLT consensus document. J Heart Lung Transplant 37(5):537–547

    PubMed  Google Scholar 

  83. Ballester M, Obrador D, Carió I et al (1990) Indium-111-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 82(6):2100–2107

    PubMed  CAS  Google Scholar 

  84. Rubin PJ, Hartman JJ, Hasapes JP et al Detection of cardiac transplant rejection with 111In-labeled lymphocytes and gamma scintigraphy

  85. Narula J, Acio ER, Narula N, Samuels LE, Fyfe B, Wood D, Fitzpatrick JM, Raghunath PN, Tomaszewski JE, Kelly C, Steinmetz N, Green A, Tait JF, Leppo J, Blankenberg FG, Jain D, Strauss HW (2001) Annexin-V imaging for noninvasive detection of cardiac allograft rejection. Nat Med 7(12):1347–1352

    PubMed  CAS  Google Scholar 

  86. Costanzo MR, Dipchand A, Starling R et al (2010) The International Society of Heart and Lung Trans-plantation guidelines for the care of heart transplant recipients. J Heart Transplant 29:914–956

    Google Scholar 

  87. Liu J, Chen Y, Wang G, Lv Q, Yang Y, Wang J, Zhang P, Liu J, Xie Y, Zhang L, Xie M (2018) Ultrasound molecular imaging of acute cardiac transplantation rejection using nanobubbles targeted to T lymphocytes. Biomaterials 162:200–207

    PubMed  CAS  Google Scholar 

  88. Liao T, Li Q, Zhang Y et al (2020) Precise treatment of acute antibody-mediated cardiac allograft rejection in rats using C4d-targeted microbubbles loaded with nitric oxide. J Heart Lung Transplant. https://doi.org/10.1016/j.healun.2020.02.002 Online ahead of print

  89. Dengler TJ, Zimmermann R, Braun K, Müller-Bardorff M, Zehelein J, Sack FU, Schnabel PA, Kübler W, Katus HA (1998) Elevated serum concentrations of cardiac troponin t in acute allograft rejection after human heart transplantation. J Am Coll Cardiol 32(2):405–412

    PubMed  CAS  Google Scholar 

  90. Wåhlander H, Kjellström C, Holmgren D (2002) Sustained elevated concentrations of cardiac troponin t during acute allograft rejection after heart transplantation in children. Transplantation 74(8):1130–1135

    PubMed  Google Scholar 

  91. Chance JJ, Segal JB, Wallerson G, Kasper E, Hruban RH, Kickler TS, Chan DW (2001) Cardiac troponin T and C-reactive protein as markers of acute cardiac allograft rejection. Clin Chim Acta 312(1-2):31–39

    PubMed  CAS  Google Scholar 

  92. Mullen JC, Bentley MJ, Scherr KD, Chorney SG, Burton NI, Tymchak WJ, Koshal A, Modry DL (2002) Troponin T and I are not reliable markers of cardiac transplant rejection. Eur J Cardiothorac Surg 22(2):233–237

    PubMed  CAS  Google Scholar 

  93. Garrido IP, Pascual-Figal DA, Nicolás F, González-Carrillo MJ, Manzano-Fernández S, Sánchez-Mas J, Valdés-Chavarri M (2009) Usefulness of serial monitoring of B-type natriuretic peptide for the detection of acute rejection after heart transplantation. Am J Cardiol 103(8):1149–1153

    PubMed  CAS  Google Scholar 

  94. Nikaein A, Spiridon C, Hunt J, Rosenthal J, Anderson A, Eichhorn E, Magee M, Dewey T, Mack M (2007) Pre-transplant level of soluble CD30 is associated with infection after heart transplantation. Clin Transplant 21(6):744–747

    PubMed  Google Scholar 

  95. Heikal NM, Bader FM, Martins TB, Pavlov IY, Wilson AR, Barakat M, Stehlik J, Kfoury AG, Gilbert EM, Delgado JC, Hill HR (2013) Immune function surveillance: association with rejection, infection and cardiac allograft vasculopathy. Transplant Proc. 45(1):376–382

    PubMed  CAS  Google Scholar 

  96. Tarazon E, Corbacho-Alonso N, Barderas MG et al (2020) Plasma CD5L and non-invasive diagnosis of acute heart rejection. J Heart Lung Transplant 39(3):257–266

    PubMed  Google Scholar 

  97. Tait BD, Süsal C, Gebel HM, Nickerson PW, Zachary AA, Claas FHJ, Reed EF, Bray RA, Campbell P, Chapman JR, Coates PT, Colvin RB, Cozzi E, Doxiadis IIN, Fuggle SV, Gill J, Glotz D, Lachmann N, Mohanakumar T, Suciu-Foca N, Sumitran-Holgersson S, Tanabe K, Taylor CJ, Tyan DB, Webster A, Zeevi A, Opelz G (2013) Consensus guidelines on the testing and clinical management issues associated with HLA and Non-HLA antibodies in transplantation. Transplantation 95(1):19–49

    PubMed  CAS  Google Scholar 

  98. Kobashigawa J, Crespo-Leiro MG, Ensminger SM, Reichenspurner H, Angelini A, Berry G, Burke M, Czer L, Hiemann N, Kfoury AG, Mancini D, Mohacsi P, Patel J, Pereira N, Platt JL, Reed EF, Reinsmoen N, Rodriguez ER, Rose ML, Russell SD, Starling R, Suciu-Foca N, Tallaj J, Taylor DO, van Bakel A, West L, Zeevi A, Zuckermann A, Consensus Conference Participants (2011) Report from a consensus conference on antibody-mediated rejection in heart transplantation. J Heart Lung Transplant. 30(3):252–269

    PubMed  Google Scholar 

  99. Colvin MM, Cook JR, Chang P, Francis G, Hsu DT, Kiernan MS, Kobashigawa JA, Lindenfeld J, Masri SC, Miller D, O'Connell J, Rodriguez ER, Rosengard B, Self S, White-Williams C, Zeevi A, American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology., American Heart Association Heart Failure and Transplantation Committee of the Council on Cardiopulmonary Critical Care, Perioperative and Resuscitation., American Heart Association Heart Failure and Transplantation Committee of the Council on Cardiovascular Disease in the Young., American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology, Council on Cardiovascular and Stroke Nursing., American Heart Association Heart Failure and Transplantation Committee of the Council on Cardiovascular Radiology and Intervention., American Heart Association Heart Failure and Transplantation Committee of the Council on Cardiovascular Surgery and Anesthesia (2015) Antibody mediated rejection in cardiac transplantation: emerging knowledge in diagnosis and management. Circulation 131:1608–1639

    PubMed  Google Scholar 

  100. Bruneval P, Angelini A, Miller D, Potena L, Loupy A, Zeevi A, Reed EF, Dragun D, Reinsmoen N, Smith RN, West L, Tebutt S, Thum T, Haas M, Mengel M, Revelo P, Fedrigo M, Duong van Huyen JP, Berry GJ (2017) The XIIIth Banff Conference on Allograft Pathology: the Banff 2015 Heart Meeting Report: improving antibody-mediated rejection diagnostics: strengths, unmet needs, and future directions. Am J Transplant. 17(1):42–53

    PubMed  CAS  Google Scholar 

  101. Ware AL, Malmberg E, Delgado JC, Hammond ME, Miller DV, Stehlik J, Kfoury A, Revelo MP, Eckhauser A, Everitt MD (2016) The use of circulating donor specific antibody to predict biopsy diagnosis of antibody-mediated rejection and to provide prognostic value after heart transplantation in children. J Heart Lung Transplant. 35(2):179–185

    PubMed  Google Scholar 

  102. Zhang Q, Hickey M, Drogalis-Kim D, Zheng Y, Gjertson D, Cadeiras M, Khuu T, Baas AS, Depasquale EC, Halnon NJ, Perens G, Alejos J, Cruz D, Ali N, Shemin R, Kwon M, Fishbein MC, Ardehali A, Deng M, Reed EF (2018) Understanding the correlation between DSA, complement activation, and antibody-mediated rejection in heart transplant recipients. Transplantation. 102(10):e431–e438

    PubMed  PubMed Central  CAS  Google Scholar 

  103. Nath DS, Ilias Basha H, Tiriveedhi V, Alur C, Phelan D, Ewald GA, Moazami N, Mohanakumar T (2010) Characterization of immune responses to cardiac self-antigens myosin and vimentin in human cardiac allograft recipients with antibody-mediated rejection and cardiac allograft vasculopathy. J Heart Lung Transplant. 29(11):1277–1285

    PubMed  PubMed Central  Google Scholar 

  104. Clerkin KJ, Farr MA, Restaino SW, Zorn E, Latif F, Vasilescu ER, Marboe CC, Colombo PC, Mancini DM (2017) Donor specific anti-HLA antibodies with antibody mediated rejection and long-term outcomes following heart transplantation. J Heart Lung Transplant. 36(5):540–545

    PubMed  Google Scholar 

  105. Wong KL, Taner T, Smith BH, Kushwaha SS, Edwards BS, Gandhi MJ, Kremers WK, Daly RC, Pereira NL (2017) Importance of routine antihuman/leukocyte antibody monitoring: de novo specific antibodies are associated with rejection and allograft vasculopathy after transplantation. Circulation 136:1350–1352

    PubMed  Google Scholar 

  106. Fedrigo M, Leone O, Burke MM et al (2015) Inflammatory cell burden and phenotype in endomyocardial biopsies with antibody-Mediated rejection (AMR): A multicenter pilot study from the AECVP. Am J Transplant 15(2):526–534. https://doi.org/10.1111/ajt.12976

    Article  PubMed  CAS  Google Scholar 

  107. Topilsky Y, Gandhi MJ, Hasin T, Voit LL, Raichlin E, Boilson BA, Schirger JA, Edwards BS, Clavell AL, Rodeheffer RJ, Frantz RP, Kushwaha SS, Lerman A, Pereira NL (2013) Donor-specific antibodies to class II antigens are associated with accelerated cardiac allograft vasculopathy: a three-dimensional volumetric intra-vascular ultrasound study. Transplantation. 95:389–396

    PubMed  PubMed Central  CAS  Google Scholar 

  108. Frank R, Molina MR, Goldberg LR, Wald JW, Kamoun M, Lal P (2014) Circulating donor-specific anti-human leukocyte antigen antibodies and complement C4d deposition are associated with the development of cardiac allograft vasculopathy. Am J Clin Pathol 142(6):809–815

    PubMed  Google Scholar 

  109. Das BB, Lacelle C, Zhang S, Gao A, Fixler D (2018) Complement (C1q) binding de novo donor specific antibodies and cardiac-allograft vasculopathy in pediatric heart transplant recipients. Transplantation. 102(3):502–509

    PubMed  PubMed Central  CAS  Google Scholar 

  110. Faulk WP, Rose M, Meroni PL, del Papa N, Torry RJ, Labarrere CA, Busing K, Crisp SJ, Dunn MJ, Nelson DR (1999) Antibodies to endothelial cells identify myocardial damage and predict development of coronary disease in patients with transplanted hearts. Hum Immunol. 60:826–832

    PubMed  CAS  Google Scholar 

  111. Torres FM, Pando MJ, Luo C et al (2017) The role of complement-fixing donor-specific antibodies identified by a C1q assay after heart transplantation. Clin Transplant 31(11):e13121

    Google Scholar 

  112. See SB, Mantell BS, Clerkib KJ et al (2020) Profiling non-HLA antibody responses in antibody-mediated rejection following heart transplantation. Am J Transplant. 20:2571–2580. https://doi.org/10.1111/ajt.15871. Online ahead of print

    Article  PubMed  CAS  Google Scholar 

  113. Gates KV, Pereira NL, Griffiths LG (2017) Cardiac non-human leukocyte antigen identification: techniques and troubles. Front Immunol 8:1332 (1-11)

    PubMed  PubMed Central  Google Scholar 

  114. Chhabra M, Alsughayyir J, Qureshi MS, Mallik M, Ali JM, Gamper I, Moseley EL, Peacock S, Kosmoliaptsis V, Goddard MJ, Linterman MA, Motallebzadeh R, Pettigrew GJ (2019) Germinal center alloantibody responses mediate progression of chronic allograft injury. Front Immunol. 9:3038. https://doi.org/10.3389/fimmu.2018.03038 eCollection 2018

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Mehra MR, Uber PA, Bentitez RM et al (2010) Gene-based bio-signature patterns and cardiac allograft rejection. Heart Fail Clin. 6(1):87–92

    PubMed  Google Scholar 

  116. Deng MC, Eisen HJ, Mehra MR et al (2006) Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling. Am J Transplant. 6(1):150–160

    PubMed  CAS  Google Scholar 

  117. Mehra MR, Kobashigawa JA, Deng MC, Fang KC, Klingler TM, Lal PG, Rosenberg S, Uber PA, Starling RC, Murali S, Pauly DF, Dedrick R, Walker MG, Zeevi A, Eisen HJ, CARGO Investigators (2007) Transcriptional signals of T-cell and corticosteroid sensitive genes are associated with future acute cellular rejection in cardiac allografts. J Heart Lung Transplant. 26(12):1255–1263

    PubMed  Google Scholar 

  118. Crespo-Leiro MG, Stypmann J, Schulz U, Zuckermann A, Mohacsi P, Bara C, Ross H, Parameshwar J, Zakliczyński M, Fiocchi R, Hoefer D, Colvin M, Deng MC, Leprince P, Elashoff B, Yee JP, Vanhaecke J (2016) Clinical usefulness of gene-expression profile to rule out acute rejection after heart transplantation: CARGO II. Eur Heart J. 37(33):2591–2601

    PubMed  PubMed Central  CAS  Google Scholar 

  119. Pham MX, Teuteberg JJ, Kfoury AG, Starling RC, Deng MC, Cappola TP, Kao A, Anderson AS, Cotts WG, Ewald GA, Baran DA, Bogaev RC, Elashoff B, Baron H, Yee J, Valantine HA, IMAGE Study Group (2010) Gene-expression profiling for rejection surveillance after cardiac transplantation. N Engl J Med. 362:1890–1900

    PubMed  CAS  Google Scholar 

  120. Moayedi Y, Foroutan F, Miller RJH, Fan CPS, Posada JGD, Alhussein M, Tremblay-Gravel M, Oro G, Luikart HI, Yee J, Shullo MA, Khush KK, Ross HJ, Teuteberg JJ (2019) Risk evaluation using gene expression screening to monitor for acute cellular rejection in heart transplant recipients. J Heart Lung Transplant. 38(1):51–58

    PubMed  Google Scholar 

  121. Crespo-Leiro MG, Barge-Caballero E, Paniagua-Martin MJ, Barge-Caballero G, Suarez-Fuentetaja N (2015) Update on immune monitoring in heart transplantation. Curr Transpl Rep 2:329–337

    Google Scholar 

  122. North PE, Ziegler E, Mahnke DK, Stamm KD, Thomm A, Daft P, Goetsch M, Liang H, Baker MA, Vepraskas A, Rosenau C, Dasgupta M, Simpson P, Mitchell ME, Tomita-Mitchell A (2020) Cell-free DNA donor fraction analysis in pediatric and adult heart transplant patients by multiplexed allele-specific quantitative PCR: validation of a rapid and highly sensitive clinical test for stratification of rejection probability. PLoS One. 15(1):e0227385. https://doi.org/10.1371/journal.pone.0227385 eCollection 2020

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Khush KK, Patel J, Pinney S, Kao A, Alharethi R, DePasquale E, Ewald G, Berman P, Kanwar M, Hiller D, Yee JP, Woodward RN, Hall S, Kobashigawa J (2019) Noninvasive detection of graft injury after heart transplant using donor-derived cell-free DNA: a prospective multicenter study. Am J Transplant. 19:2889–2899

    PubMed  PubMed Central  CAS  Google Scholar 

  124. Richmond ME, Zangwill SD, Kindel SJ (2019) Donor fraction cell-free DNA and rejection in adult and pediatric heart transplantation. J Heart Lung Transplant S1053-2498(19):31767-X

    Google Scholar 

  125. Xin A, Lee MGY, Hu Y, Ignjatovic V, Shi WY, Shipp A, Praporski S, Kallies A, Weintraub RG, Monagle PT, Smyth GK, Konstantinov IE (2018) Identifying low-grade cellular rejection after heart transplantation in children by using gene expression profiling. Physiol Genomics 50:190–196

    PubMed  CAS  Google Scholar 

  126. De Vlaminck I, Valantine HA, Snyder TM et al (2014) Circulating cell-free DNA enables non-invasive diagnosis of heart transplant rejection. Sci Transl Med 6(241):241ra77

    PubMed  PubMed Central  Google Scholar 

  127. Duong Van Huyen J-P, Tible M, Gay A et al (2014) MicroRNAs as non-invasive biomarkers of heart transplant rejection. Eur Heart J. 35(45):3194–3202

    PubMed  Google Scholar 

  128. Sukma Dewi I, Hollander Z, Lam KK et al (2017) Association of serum miR-142-3p and miR-101-3p levels with acute cellular rejection after heart transplantation. PLoS One 12(1):e0170842 (1-16)

    PubMed  PubMed Central  Google Scholar 

  129. Andrikopoulou E, Mather PJ (2014) Current insights: use of Immuknow in heart transplant recipients. Prog Transplant. 24(1):44–50

    PubMed  Google Scholar 

  130. Kobashigawa JA, Kiyosaki KK, Patel JK et al (2010) Benefit of immune monitoring in heart trans-plant patients using ATP production in activated lymphocytes. J Heart Lung Transplant. 29(5):504–508

    PubMed  Google Scholar 

  131. Wong M-S, Boucek R, Kemna M (2014) Immune cell function assay in pediatric heart transplant recipients. Pediatr Transplant. 18(5):485–490

    PubMed  CAS  Google Scholar 

  132. Clerkin KJ, Restaino SW, Zorn E, Vasilescu ER, Marboe CC, Mancini DM (2016) The effect of timing and graft dysfunction on survival and cardiac allograft vasculopathy in antibody-mediated rejection. J Heart Lung Transplant 35:1059–1066

    PubMed  PubMed Central  Google Scholar 

  133. Eisen H (2001) Left ventricular dysfunction after cardiac transplantation: etiologies, diagnosis and treatment. In Norman DJ and Turka LA. eds. Primer on transplantation. 2nd Edition, American Society of Transplantation. 366-69,

  134. Lund LH, Khush KK, Cherikh WS et al (2017) The Registry of the International Society for Heart and Lung Transplantation: thirty-fourth adult heart transplantation report−2017. J Heart Lung Transplant. 36(10):1037–1046

    PubMed  Google Scholar 

  135. Kfoury AG, Snow GL, Budge D, Alharethi RA, Stehlik J, Everitt MD, Miller DV, Drakos SG, Reid BB, Revelo MP, Gilbert EM, Selzman CH, Bader FM, Connelly JJ, Hammond MEH (2012) A longitudinal study of the course of asymptomatic antibody-mediated rejection in heart transplantation. J Heart Lung Transplant 31:46–51

    PubMed  Google Scholar 

  136. Michaels PJ, Espejo ML, Kobashigawa J, Alejos JC, Burch C, Takemoto S, Reed EF, Fishbein MC (2003) Humoral rejection in cardiac transplantation: risk factors, hemodynamic consequences and relationship to transplant coronary artery disease. J Heart Lung Transplant. 22(1):58–69

    PubMed  Google Scholar 

  137. Afzali B, Chapman E, Racape M et al (2017) Molecular assessment of microcirculation injury in formalin-fixed human cardiac allograft biopsies with antibody-mediated rejection. Am J Transplant. 30:1214–1220

    Google Scholar 

  138. Loupy A (2017) Duong Van Huyen JP, Hidalgo L. et al. Gene expression profiling for the identification and classification of antibody-mediated heart rejection. Circulation. 135(10):917–935

    PubMed  CAS  Google Scholar 

  139. Chih S, Tinckam KJ, Ross HJ (2013) A survey of current practice of antibody-mediated rejection in heart transplantation. Am J Transplant. 13:1069–1074

    PubMed  CAS  Google Scholar 

  140. Dandel M, Müller J, Hummel M, Meyer R, Ewert R, Hetzer R (2002) Efficiency and reliability of early post-operative noninvasive rejection monitoring. Transplant Proc 34:2174–2177

    PubMed  CAS  Google Scholar 

  141. Berry GJ, Angelini A, Burke MM, Bruneval P, Fishbein MC, Hammond E, Miller D, Neil D, Revelo MP, Rodriguez ER, Stewart S, Tan CD, Winters GL, Kobashigawa J, Mehra MR (2011) The ISHLT working formulation for pathologic diagnosis of antibody-mediated rejection in heart transplantation: evolution and current status (2005–2011). J Heart Lung Transplant 30(6):601–611

    PubMed  Google Scholar 

  142. Kfouri AG, Renlund GB, Snow GL et al (2009) A clinical correlation study of severity of antibody-mediated rejection and cardiovascular mortality in heart transplantation. J Heart Lung Transplant. 28:51–57

    Google Scholar 

  143. Almuti K, Haythe J, Dwyer E, Itescu S, Burke E, Green P, Marboe C, Mancini D (2007) The changing pattern of humoral rejection in cardiac transplant recipients. Transplantation 84:498–503

    PubMed  Google Scholar 

  144. Wu G, Kobashigaba J, Fischbein M et al (2009) Asymptomatic antibody-mediated rejection after heart transplantation predicts poor outcomes. J Heart Lung Transplant. 28:417–422

    PubMed  Google Scholar 

  145. Dandel M, Hummel M, Müller J et al (2001) Clinical value of non-invasive cardiac rejection monitoring by tissue Doppler and telemetric intramyocardial electrogram recordings during the first post-transplant year. Circulation (Suppl.) 104(17):II-364

    Google Scholar 

  146. Hamour IM, Burke MM, Bell AD, Panicker MG, Banerjee R, Banner NR (2008) Limited utility of endomyocardial biopsy in the first year after heart transplantation. Transplantation. 85(7):969–974

    PubMed  Google Scholar 

  147. Dandel M, Müller J, Hummel M et al (2002) Invasive and non-invasive cardiac rejection monitoring during the first post-transplant year: comparison of two different strategies. American Journal of Transplantation 2(Suppl.3):183

    Google Scholar 

  148. Weckbach LW, Maurer U, Schramm R et al (2017) Lower frequency routine surveillance endomyocardial biopsies after heart transplantation. PLoS One. 2(8):e0182880 1-12

    Google Scholar 

  149. Dandel M, Lehmkuhl HB, Knosala C, Hetzer R (2010) Impact of different maintenance immuno-suppressive therapy strategies on patient’s outcome after heart transplantation. Transpl Immunol 23:93–103

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael Dandel.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dandel, M., Hetzer, R. Non-invasive cardiac allograft rejection surveillance: reliability and clinical value for prevention of heart failure. Heart Fail Rev 26, 319–336 (2021). https://doi.org/10.1007/s10741-020-10023-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-020-10023-3

Keywords

Navigation