Skip to main content
SpringerLink
Log in

Identification of Preoperative Risk Factors for the Development of Cardiac Allograft Vasculopathy: A Systematic Review

  • Hot Topic (Jose Diaz, Section Editor)
  • Published:
Current Surgery Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The purpose of this systematic review was to analyze the current literature and identify all known preoperative risk factors associated with an increased incidence of cardiac allograft vasculopathy.

Recent Findings

A total of 7 independent preoperative risk factors for cardiac allograft vasculopathy were identified, namely T. gondii seropositivity (HR 4.39, 1.26–15.62, p < 0.02), elevated body mass index (HR 1.116, 1.015–1.23, p < 0.02), 2–1 haptoglobin phenotype (HR 2.73, 1.03–7.19, p < 0.01), elevated low-density lipoproteins (OR 2.14, 1.02–4.46, p < 0.04), single-nucleotide polymorphism -201 matching (HR 11.9, 4.3–32.9, p < 0.01), stroke cause of death (HR 1.47, 1.04–2.09, p < 0.03), and pre-transplant hemodynamic instability (HR 1.79, 1.15–2.77, p < 0.01).

Summary

Cardiac allograft vasculopathy is the leading cause of death in patients who survive more than a few years following transplantation and is likely the limiting factor in expanding the average life expectancy post-transplant. The development of therapeutics targeting the multifactorial etiology of this vasculopathy would undoubtedly provide hope for patients whose time is currently limited.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data Availability

All data extracted to generate the results of this systematic review is included within Table 1, where it is linked with the corresponding research it was extracted from.

References

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

  1. ••Shetty M, Chowdhury YS. Heart Transplantation Allograft Vasculopathy. [Updated 2023 May 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK555999/ This article was very formative in this review, because it contains the most current, peer-reviewed epidemiological statistics on CAV. Largely, the importance of our review is derived from the vast mortality of CAV, which was quantified based on the contents of this article.

  2. Ramzy D, Rao V, Brahm J, Miriuka S, Delgado D, Ross HJ. Cardiac allograft vasculopathy: a review. Can J Surg. 2005;48(4):319–27.

    PubMed  PubMed Central  Google Scholar 

  3. Anyanwu A, Treasure T. Prognosis after heart transplantation: transplants alone cannot be the solution for end stage heart failure. BMJ. 2003;326(7388):509–10. https://doi.org/10.1136/bmj.326.7388.509.

    Article  PubMed  PubMed Central  Google Scholar 

  4. ••Pober JS, Chih S, Kobashigawa J, Madsen JC, Tellides G. Cardiac allograft vasculopathy: current review and future research directions. Cardiovasc Res. 2021 Nov 22;117(13):2624-2638. doi: https://doi.org/10.1093/cvr/cvab259. This article was very significant in this review because it outlined the increasing mortality of heart transplant recipients due to CAV as time PT increased. The foundation for the claims on the potential for CAV to be the limiting factor in extending the average life expectancy for heart transplant recipients is derived partially from this article.

  5. Chih S, Chong AY, Mielniczuk LM, Bhatt DL, Beanlands RS. Allograft vasculopathy: the Achilles’ heel of heart transplantation. J Am Coll Cardiol. 2016;68(1):80–91. https://doi.org/10.1016/j.jacc.2016.04.033.

    Article  PubMed  Google Scholar 

  6. Cassar A, Holmes DR Jr, Rihal CS, Gersh BJ. Chronic coronary artery disease: diagnosis and management. Mayo Clin Proc. 2009;84(12):1130–46. https://doi.org/10.4065/mcp.2009.0391.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Segura AM, Buja LM. Cardiac allograft vasculopathy: a complex multifactorial sequela of heart transplantation. Tex Heart Inst J. 2013;40(4):400–2.

    PubMed  PubMed Central  Google Scholar 

  8. Pighi M, Gratta A, Marin F, Bellamoli M, Lunardi M, Fezzi S, Zivelonghi C, Pesarini G, Tomai F, Ribichini F. Cardiac allograft vasculopathy: Pathogenesis, diagnosis and therapy. Transplant Rev (Orlando). 2020;34(4): 100569. https://doi.org/10.1016/j.trre.2020.100569.

    Article  PubMed  Google Scholar 

  9. Skorić B, Čikeš M, Ljubas Maček J, Baričević Ž, Škorak I, Gašparović H, Biočina B, Miličić D. Cardiac allograft vasculopathy: diagnosis, therapy, and prognosis. Croat Med J. 2014;55(6):562–76. https://doi.org/10.3325/cmj.2014.55.562.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. US Department of Health and Human Services. (n.d.). OPTN/SRTR 2019 Annual data report: Heart - health resources and ... Scientific Registry of Transplant Recipients. https://srtr.transplant.hrsa.gov/annual_reports/2019/Heart.aspx

  11. •• Suarez-Pierre A, Lui C, Zhou X, Giuliano K, Etchill E, Almaraz-Espinoza A, Crawford TC, Fraser CD 3rd, Whitman GJ, Choi CW, Higgins RS, Kilic A. Long-term Survival After Heart Transplantation: A Population-based Nested Case-Control Study. Ann Thorac Surg. 2021 Mar;111(3):889-898. https://doi.org/10.1016/j.athoracsur.2020.05.163. This article is significant to this review, because it is a large-scale, peer-review case control study analyzing more than 30,000 heart transplant recipients. Thorough demographic data was collected including cause of death.

  12. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan—A web and mobile app for systematic reviews. Syst Rev. 2016;5:210. https://doi.org/10.1186/s13643-016-0384-4.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Review Manager Web (RevMan Desktop). Version 5.4.1. The Cochrane Collaboration, (2023). https://login.cochrane.org/

  14. Arora S, Jenum PA, Aukrust P, Rollag H, Andreassen AK, Simonsen S, Gude E, Fiane AE, Geiran O, Gullestad L. Pre-transplant Toxoplasma gondii seropositivity among heart transplant recipients is associated with an increased risk of all-cause and cardiac mortality. J Am Coll Cardiol. 2007;50(20):1967–72. https://doi.org/10.1016/j.jacc.2007.07.068.

    Article  PubMed  Google Scholar 

  15. Densem CG, Wassel J, Cooper A, Yonan N, Brooks NH, Keevil B. Haptoglobin phenotype correlates with development of cardiac transplant vasculopathy. J Heart Lung Transplant. 2004;23(1):43–9. https://doi.org/10.1016/S1053-2498(03)00061-5.

    Article  PubMed  Google Scholar 

  16. Javaheri A, Molina M, Zamani P, Rodrigues A, Novak E, Chambers S, Stutman P, Maslanek W, Williams M, Lilly SM, Heeger P, Sayegh MH, Chandraker A, Briscoe DM, Daly KP, Starling R, Ikle D, Christie J, Eduardo Rame J, Goldberg LR, Billheimer J, Rader DJ. Cholesterol efflux capacity of high-density lipoprotein correlates with survival and allograft vasculopathy in cardiac transplant recipients. J Heart Lung Transplant. 2016;35(11):1295–302. https://doi.org/10.1016/j.healun.2016.06.022.

    Article  PubMed  PubMed Central  Google Scholar 

  17. • Kondziella, C., Fluschnik, N., Weimann, J., Bernhard, A. M., Schrage, B., Blankenberg, S., Reichenspurner, H., Kirchhof, P., Schnabel, R. B., & Magnussen, C. (2022). Sex Differences in Clinical Characteristics and Outcomes in Patients Undergoing Heart Transplantation. Journal of Heart and Lung Transplantation, 41(4), S152. https://doi.org/10.1016/j.healun.2022.01.361. This study significantly contributed to this review by performing multivariable analysis of sex differences in outcomes of heart transplant patients via a prospective cohort study of more than 49,000 patients. Their study found that male gender was a risk factor CAV, but when this finding was subjected to meta-analysis, it failed to meet significance in our study.

  18. Lazarte J, Goldraich L, Manlhiot C, Billia F, Ross H, Rao V, Delgado D. Human leukocyte antigen G single-nucleotide polymorphism-201 (CC–CC) donor–recipient genotype matching as a predictor of severe cardiac allograft vasculopathy. J Heart Lung Transplant. 2016;35(9):1101–7. https://doi.org/10.1016/j.healun.2016.04.014.

    Article  PubMed  Google Scholar 

  19. Van Keer JM, Van Aelst LNL, Rega F, Droogne W, Voros G, Meyns B, Vanhaecke J, Emonds MP, Janssens S, Naesens M, Van Cleemput J. Long-term outcome of cardiac allograft vasculopathy: importance of the International Society for Heart and Lung Transplantation angiographic grading scale. J Heart Lung Transplant. 2019;38(11):1189–96. https://doi.org/10.1016/j.healun.2019.08.005.

    Article  PubMed  Google Scholar 

  20. Evan P. Kransdorf, Jon A. Kobashigawa, 44 - Heart Transplantation, Editor(s): G. Michael Felker, Douglas L. Mann, In Companion to Braunwald’s Heart Disease, Heart Failure: a Companion to Braunwald’s Heart Disease (Fourth Edition), Elsevier, 2020, Pages 631–648.e4, https://doi.org/10.1016/B978-0-323-60987-6.00044-2.

Download references

Funding

This review did not receive any funding.

Author information

Authors and Affiliations

  1. Osteopathic Medicine, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, 3400 Gulf to Bay Blvd, Clearwater, FL, 33759, USA

    Will S. Roberts, Annalena Pirovic, Adrian Ionescu, Michael Ryan & Sarah Schaffer

  2. Foundational Sciences, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Clearwater, USA

    Hoang Nguyen

Authors
  1. Will S. Roberts
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Annalena Pirovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adrian Ionescu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Ryan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sarah Schaffer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hoang Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization – WSR Database Search String – WSR Methodology – WSR Abstract Screening – WSR, AP, AI, MR, SS Full-Text Screening –WSR, AP, AI, MR, SS Data Extraction – WSR Data Curation – WSR Data Analysis – WSR Supervision –WSR, HN Manuscript Writing – WSR, AP, AI, MR, SS Manuscript Reviewing/Editing – WSR, AP, AI, MR, SS, HN Corresponding Author – WSR

Corresponding author

Correspondence to Will S. Roberts.

Ethics declarations

Conflict of interest

The authors of this review do not have any conflicts of interest to declare.

Human and Animal Rights Informed Consent

All studies with human or animal subjects are published and followed ethical standards.

Additional information

Publisher's Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Roberts, W.S., Pirovic, A., Ionescu, A. et al. Identification of Preoperative Risk Factors for the Development of Cardiac Allograft Vasculopathy: A Systematic Review. Curr Surg Rep 12, 104–110 (2024). https://doi.org/10.1007/s40137-024-00393-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40137-024-00393-0

Keywords

Search

Navigation