Log in

Intravascular Imaging for Assessment of Cardiac Allograft Vasculopathy Following Heart Transplantation

  • Intravascular Imaging (A Truesdell, Section Editor)
  • Published:
Current Cardiovascular Imaging Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Cardiac allograft vasculopathy (CAV) is a significant cause of morbidity and mortality in the post-cardiac transplant patient population. Current guidelines recommend annual angiographic surveillance for CAV; however, angiography alone has several limitations and can lead to systematic underestimation of disease burden and the inability to sensitively track disease progression. We provide an overview of intravascular imaging in the initial and longitudinal evaluation of CAV, with a focus on the use of intravascular ultrasound (IVUS).

Recent Findings

Multiple studies have demonstrated that progression of maximal intimal thickness (MIT) on serial IVUS evaluation, particularly ≥ 0.5 mm over the first year, post-transplant, is predictive of both future development of angiographically significant CAV as well as major adverse cardiac events, including graft loss and mortality. There are also emerging data that in vivo plaque characterization, as assessed by the attenuated-signal plaque score or by virtual histology intravascular ultrasound (VH-IVUS), may provide prognostic value in this population. OCT-derived intimal measurements have been noted to correlate well with IVUS findings and may also aid in early identification of CAV. In addition to early identification and prognostication, several studies have used intravascular imaging to assess therapeutic impact of various immunosuppressive regimens on progression of established CAV.

Summary

Intravascular ultrasound, and more recently, optical coherence tomography (OCT) have emerged as valuable adjuncts to angiography in the evaluation of CAV, particularly with regard to early detection, objective prognostication, and differentiation of CAV from donor-derived coronary artery disease (CAD). Furthermore, intravascular imaging may guide changes to the immunosuppressive regimen and/or percutaneous coronary intervention, when necessary.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Kennedy LJ, Weissman IL. Dual origin of intimal cells in cardiac-allograft arteriosclerosis. N Engl J Med. 1971 [cited 2019 Feb 18];285:884–887. Available from: http://www.ncbi.nlm.nih.gov/pubmed/4939537.

    Article  Google Scholar 

  2. Gotlieb AI, Crosby D, Lemire GG, Huang S. A study of human cardiac allograft in a patient with four-year survival. Can Med Assoc J. 1974 [cited 2019 Feb 18];110:154–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/4589396.

  3. Agarwal S, Parashar A, Kapadia SR, Tuzcu EM, Modi D, Starling RC, Oliveira GH. Long-term mortality after cardiac allograft vasculopathy. JACC Hear Fail. 2014 [cited 2019 Apr 9];2:281–288. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24952696.

    PubMed  Google Scholar 

  4. Shah NR, Blankstein R, Villines T, Imran H, Morrison AR, Cheezum MK. Coronary CTA for surveillance of cardiac allograft vasculopathy. Curr Cardiovasc Imaging Rep. 2018 [cited 2019 Jan 14];11:26. Available from: https://doi.org/10.1007/s12410-018-9467-z.

  5. Costanzo MR, Dipchand A, Starling R, Anderson A, Chan M, Desai S, Fedson S, Fisher P, Gonzales-Stawinski G, Martinelli L, McGiffin D, Parisi F, Smith J, Taylor D, Meiser B, Webber S, Baran D, Carboni M, Dengler T, Feldman D, Frigerio M, Kfoury A, Kim D, Kobashigawa J, Shullo M, Stehlik J, Teuteberg J, Uber P, Zuckermann A, Hunt S, Burch M, Bhat G, Canter C, Chinnock R, Crespo-Leiro M, Delgado R, Dobbels F, Grady KWK, Lamour J, Parry G, Patel J, Pini D, Pinney S, Towbin J, Wolfel G, Delgado D, Eisen H, Goldberg L, Hosenpud J, Johnson M, Keogh A, Lewis C, O’Connell J, Rogers J, Ross H, Russell S, Vanhaecke J. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Hear Lung Transplant. 2010 [cited 2019 Jan 14];29:914–956. Available from: http://www.jhltonline.org.

    Article  Google Scholar 

  6. Haddad M, Pflugfelder PW, Guiraudon C, Novick RJ, McKenzie FN, Menkis A, Kostuk WJ. Angiographic, pathologic, and clinical relationships in coronary artery disease in cardiac allografts. J Hear Lung Transplant. 2005 [cited 2019 Apr 9];24:1218–1225. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16143236.

    Article  Google Scholar 

  7. Ramzy D, Rao V, Brahm J, Miriuka S, Delgado D, Ross HJ. Cardiac allograft vasculopathy: a review. Can J Surg. 2005 [cited 2018 Dec 26];48:319–27. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16149368.

  8. Tsutsui H, Ziada KM, Schoenhagen P, Iyisoy A, Magyar WA, Crowe TD, Klingensmith JD, Vince DG, Rincon G, Hobbs RE, Yamagishi M, Nissen SE, Tuzcu EM. Lumen loss in transplant coronary artery disease is a biphasic process involving early intimal thickening and late constrictive remodeling: results from a 5-year serial intravascular ultrasound study. Circulation. 2001 [cited 2019 Apr 9];104:653–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11489770.

    Article  CAS  Google Scholar 

  9. van Loosdregt J, van Oosterhout MFM, Bruggink AH, van Wichen DF, van Kuik J, de Koning E, Baan CC, de Jonge N, Gmelig-Meyling FHJ, de Weger RA. The chemokine and chemokine receptor profile of infiltrating cells in the wall of arteries with cardiac allograft vasculopathy is indicative of a memory T-helper 1 response. Circulation. 2006 [cited 2019 Apr 9];114:1599–1607. Available from: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.105.597526.

    Article  CAS  Google Scholar 

  10. Lee MS, Finch W, Weisz G, Kirtane AJ. Cardiac allograft vasculopathy. Rev Cardiovasc Med. 2011 [cited 2019 Apr 9];12:143–52. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22080925.

  11. Radovancevic B, Poindexter S, Birovljev S, Velebit V, McAllister HA, Duncan JM, Vega D, Lonquist J, Burnett CM, Frazier OH. Risk factors for development of accelerated coronary artery disease in cardiac transplant recipients. Eur J Cardiothorac Surg. 1990 [cited 2019 Apr 9];4:309–12; discussion 313. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2361019.

    Article  CAS  Google Scholar 

  12. Schmauss D, Weis M. Cardiac allograft vasculopathy recent developments. 2008 [cited 2018 Dec 26];Available from: http://circ.ahajournals.org.

  13. Mehra MR, Crespo-Leiro MG, Dipchand A, Ensminger SM, Hiemann NE, Kobashigawa JA, Madsen J, Parameshwar J, Starling RC, Uber PA. International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy—2010. J Hear Lung Transplant. 2010 [cited 2019 Jan 14];29:717–727. Available from: http://www.jhltonline.org.

    Article  Google Scholar 

  14. Chih S, Chong AY, Mielniczuk LM, Bhatt DL, Beanlands RSB. Allograft vasculopathy: the Achilles’ heel of heart transplantation. J Am Coll Cardiol. 2016 [cited 2019 Apr 9];68:80–91. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27364054.

    Article  Google Scholar 

  15. Harris PE, Bian H, Reed EF. Induction of high affinity fibroblast growth factor receptor expression and proliferation in human endothelial cells by anti-HLA antibodies: a possible mechanism for transplant atherosclerosis. J Immunol. 1997 [cited 2019 Apr 9];159:5697–704. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9548514.

  16. **dra PT, ** Y-P, Rozengurt E, Reed EF. HLA class I antibody-mediated endothelial cell proliferation via the mTOR pathway. J Immunol. 2008 [cited 2019 Apr 9];180:2357–66. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18250445.

    Article  CAS  Google Scholar 

  17. Tambur AR, Pamboukian S V, Costanzo M-R, Herrera ND, Dunlap S, Montpetit M, Heroux A. The presence of HLA-directed antibodies after heart transplantation is associated with poor allograft outcome. Transplantation. 2005 [cited 2019 Apr 9];80:1019–25. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16278580.

    Article  Google Scholar 

  18. Kobashigawa JA, Tobis JM, Starling RC, Tuzcu EM, Smith AL, Valantine HA, Yeung AC, Mehra MR, Anzai H, Oeser BT, Abeywickrama KH, Murphy J, Cretin N. Multicenter intravascular ultrasound validation study among heart transplant recipients: outcomes after five years. J Am Coll Cardiol. 2005 [cited 2018 Jul 7];45:1532–1537. Available from: https://www.sciencedirect.com/science/article/pii/S0735109705004651?via%3Dihub.

  19. Taylor DO, Stehlik J, Edwards LB, Aurora P, Christie JD, Dobbels F, Kirk R, Kucheryavaya AY, Rahmel AO, Hertz MI. Registry of the International Society for Heart and Lung Transplantation: Twenty-sixth Official Adult Heart Transplant Report-2009. J Heart Lung Transplant. 2009 [cited 2019 Apr 9];28:1007–22. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19782283.

    Article  Google Scholar 

  20. Stehlik J, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dipchand AI, Dobbels F, Kirk R, Rahmel AO, Hertz MI. The Registry of the International Society for Heart and Lung Transplantation: 29th Official Adult Heart Transplant Report-2012. J Heart Lung Transplant. 2012 [cited 2018 Jul 19];Available from: http://www.jhltonline.org.

  21. Uretsky BF, Murali S, Reddy PS, Rabin B, Lee A, Griffith BP, Hardesty RL, Trento A, Bahnson HT. Development of coronary artery disease in cardiac transplant patients receiving immunosuppressive therapy with cyclosporine and prednisone. Circulation. 1987 [cited 2019 Apr 9];76:827–834. Available from: https://www.ahajournals.org/doi/10.1161/01.CIR.76.4.827

    Article  CAS  Google Scholar 

  22. Javaheri A, Saha NN, Lilly SM. How to approach the assessment of cardiac allograft vasculopathy in the modern era: review of invasive imaging modalities. Curr Heart Fail Rep. 2016 [cited 2019 Feb 18];13:86–91. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26879390.

    Article  Google Scholar 

  23. Gao S-Z, Alderman EL, Schroeder JS, Silverman JF, Hunt SA. Accelerated coronary vascular disease in the heart transplant patient: coronary arteriographic findings. J Am Coll Cardiol. 1988 [cited 2019 Aug 25];12:334–340. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3292629.

    Article  CAS  Google Scholar 

  24. Guddeti RR, Matsuo Y, Matsuzawa Y, Aoki T, Lerman LO, Kushwaha SS, Lerman A. Clinical implications of intracoronary imaging in cardiac allograft vasculopathy. Circ Cardiovasc Imaging. 2015 [cited 2019 Feb 18];8. Available from: https://www.ahajournals.org/doi/10.1161/CIRCIMAGING.114.002636

  25. St Goar FG, Pinto FJ, Alderman EL, Valantine HA, Schroeder JS, Gao SZ, Stinson EB, Popp RL. Intracoronary ultrasound in cardiac transplant recipients. In vivo evidence of “angiographically silent” intimal thickening. Circulation. 1992 [cited 2018 Jul 10];85:979–87. Available from: http://www.ncbi.nlm.nih.gov/pubmed/1537134.

    Article  CAS  Google Scholar 

  26. König A, Kilian E, Rieber J, Schiele TM, Leibig M, Sohn H-Y, Reichart B, Klauss V. Assessment of early atherosclerosis in de novo heart transplant recipients: analysis with intravascular ultrasound-derived radiofrequency analysis. J Hear Lung Transplant. 2008 [cited 2019 May 27];27:26–30. Available from: https://www.sciencedirect.com/science/article/pii/S1053249807007747.

    Article  Google Scholar 

  27. Sharples LD, Jackson CH, Parameshwar J, Wallwork J, Large SR. Diagnostic accuracy of coronary angiography and risk factors for post-heart-transplant cardiac allograft vasculopathy. Transplantation. 2003 [cited 2018 Dec 26];76:679–682. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12973108.

    Article  Google Scholar 

  28. Wali E, Nathan S. What is the clinical utility of intravascular ultrasound? Curr Cardiol Rep. 2018 [cited 2019 Mar 14];20:122. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30267327.

  29. Jagadeesan V, Retzer EM, Nathan S. Intravascular ultrasound: instrumentation and technique. In: Lang RM, Goldstein SA, Kronzon I, Khanderia BK, Mor-Avi V, editors. ASE’s comprehensive echocardiography: Elsevier; 2015. p. 75–8.

  30. Retzer EM, Jagadeesan V, Nathan S. Intravascular ultrasound: applications and limitations. In: Lang R, Goldstein SA, Kronzon I, Khanderia BK, Mor-Avi V, editors. ASE’s comprehensive echocardiography. 2015.

  31. Matthews SD, Frishman WH. A review of the clinical utility of intravascular ultrasound and optical coherence tomography in the assessment and treatment of coronary artery disease. Cardiol Rev. 2017;25:68–76.

    Article  Google Scholar 

  32. Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, Khot UN, Lange RA, Mauri L, Mehran R, Moussa ID, Mukherjee D, Nallamothu BK, Ting HH, Albert N, Creager MA, Ettinger SM, Halperin JL, Hochman JS, Kushner FG, Magnus Ohman E, Stevenson W, Yancy CW. ACCF/AHA/SCAI Practice Guideline 2011 ACCF/AHA/SCAI Guideline for percutaneous coronary intervention: executive summary a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. 2011 [cited 2018 Jul 23];Available from: http://circ.ahajournals.org.

  33. Tuzcu EM, Kapadia SR, Sachar R, Ziada KM, Crowe TD, Feng J, Magyar WA, Hobbs RE, Starling RC, Young JB, McCarthy P, Nissen SE. Intravascular ultrasound evidence of angiographically silent progression in coronary atherosclerosis predicts long-term morbidity and mortality after cardiac transplantation. J Am Coll Cardiol. 2005 [cited 2018 Jul 8];45:1538–1542. Available from: https://www.sciencedirect.com/science/article/pii/S0735109705004663

    Article  Google Scholar 

  34. Potena L, Masetti M, Sabatino M, Bacchi-Reggiani ML, Pece V, Prestinenzi P, Dall’ara G, Taglieri N, Saia F, Fallani F, Magnani G, Rapezzi C, Grigioni F. Interplay of coronary angiography and intravascular ultrasound in predicting long-term outcomes after heart transplantation. 2015 [cited 2019 Mar 14];34:1146–1153. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25843518.

  35. König A, Kilian E, Sohn H-Y, Rieber J, Schiele TM, Siebert U, Gothe RM, Reichart B, Klauss V. Assessment and characterization of time-related differences in plaque composition by intravascular ultrasound–derived radiofrequency analysis in heart transplant recipients. J Hear Lung Transplant. 2008 [cited 2019 Apr 15];27:302–309. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18342753.

    Article  Google Scholar 

  36. Raichlin E, Bae J-H, Kushwaha SS, Lennon RJ, Prasad A, Rihal CS, Lerman A. Inflammatory burden of cardiac allograft coronary atherosclerotic plaque is associated with early recurrent cellular rejection and predicts a higher risk of vasculopathy progression. J Am Coll Cardiol. 2009 [cited 2019 Mar 26];53:1279–1286. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19358941.

    Article  Google Scholar 

  37. Kubo T, Matsuo Y, Ino Y, Tanimoto T, Ishibashi K, Komukai K, Kitabata H, Tanaka A, Kimura K, Imanishi T, Akasaka T. Optical coherence tomography analysis of attenuated plaques detected by intravascular ultrasound in patients with acute coronary syndromes. Cardiol Res Pract. 2011 [cited 2019 Aug 25];2011:687515. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21941667.

  38. Xu K, Mintz GS, Kubo T, Wu X, Guo N, Yang J, Witzenbichler B, Guagliumi G, Brodie B, Dressler O, Cristea E, Parise H, Mehran R, Stone GW, Maehara A. Long-term follow-up of attenuated plaques in patients with acute myocardial infarction: an intravascular ultrasound substudy of the HORIZONS-AMI trial. Circ Cardiovasc Interv. 2012 [cited 2019 Aug 25];5:185–92. Available from: https://www.ahajournals.org/doi/10.1161/CIRCINTERVENTIONS.111.964684

    Google Scholar 

  39. Okada K, Fearon WF, Luikart H, Kitahara H, Otagiri K, Tanaka S, Kimura T, Yock PG, Fitzgerald PJ, Yeung AC, Valantine HA, Khush KK, Honda Y. Attenuated-signal plaque progression predicts long-term mortality after heart transplantation. J Am Coll Cardiol. 2016 [cited 2018 Jul 19];68:382–392. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27443435.

    Article  Google Scholar 

  40. Kume T, Akasaka T, Kawamoto T, Watanabe N, Toyota E, Neishi Y, Sukmawan R, Sadahira Y, Yoshida K. Assessment of coronary intima-media thickness by optical coherence tomography: comparison with intravascular ultrasound. Circ J. 2005 [cited 2019 May 27];69:903–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16041157.

    Article  Google Scholar 

  41. Cassar A, Matsuo Y, Herrmann J, Li J, Lennon RJ, Gulati R, Lerman LO, Kushwaha SS, Lerman A. Coronary atherosclerosis with vulnerable plaque and complicated lesions in transplant recipients: new insight into cardiac allograft vasculopathy by optical coherence tomography. Eur Heart J. 2013 [cited 2019 May 27];34:2610–2617. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23801824.

    Article  Google Scholar 

  42. Khandhar SJ, Yamamoto H, Teuteberg JJ, Shullo MA, Bezerra HG, Costa MA, Selzer F, Lee JS, Marroquin OC, McNamara DM, Mulukutla SR, Toma C. Optical coherence tomography for characterization of cardiac allograft vasculopathy after heart transplantation (OCTCAV study). J Hear Lung Transplant. 2013 [cited 2019 May 27];32:596–602. Available from: https://www.sciencedirect.com/science/article/pii/S1053249813011303?via%3Dihub#bib10

    Article  Google Scholar 

  43. Naesens M, Kuypers DRJ, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol. 2009 [cited 2019 Aug 25];4:481–508. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19218475.

    Article  CAS  Google Scholar 

  44. Kobashigawa JA, Pauly DF, Starling RC, Eisen H, Ross H, Wang S-S, Cantin B, Hill JA, Lopez P, Dong G, Nicholls SJ, A2310 IVUS Substudy Investigators. Cardiac allograft vasculopathy by intravascular ultrasound in heart transplant patients. JACC Hear Fail. 2013 [cited 2018 Jul 10];1:389–399. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24621971.

  45. Asleh R, Briasoulis A, Kremers WK, Adigun R, Boilson BA, Pereira NL, Edwards BS, Clavell AL, Schirger JA, Rodeheffer RJ, Frantz RP, Joyce LD, Maltais S, Stulak JM, Daly RC, Tilford J, Choi W-G, Lerman A, Kushwaha SS. Long-term sirolimus for primary immunosuppression in heart transplant recipients. J Am Coll Cardiol. 2018 [cited 2019 Apr 15];71:636–650. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29420960.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sandeep Nathan.

Ethics declarations

Conflict of Interest

All authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

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

This article is part of the Topical Collection on Intravascular Imaging

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wali, E., Lee, L. & Nathan, S. Intravascular Imaging for Assessment of Cardiac Allograft Vasculopathy Following Heart Transplantation. Curr Cardiovasc Imaging Rep 13, 7 (2020). https://doi.org/10.1007/s12410-020-9525-1

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s12410-020-9525-1

Keywords

Navigation