Allograft reoperation for organ shortage crisis?—time for stronger evidence for reoperation guidelines after transplantation

Heart transplantation (HTx) remains the gold standard treatment for advanced heart failure (1,2) with a reported median survival of >10 years (3). Survival after HTx has been continuously improving over the years leading to an increasing number of patients with late cardiac pathologies such as single- or multi-valvular diseases. A subset of these patients ultimately requires cardiac reoperation. Currently, there are no clear guidelines for the indications of cardiac surgery after HTx, and in cases of cardiac allograft failure re-transplantation is rather considered. However, re-transplantation is associated with lower survival rates compared to primary HTx, even when patients are carefully selected (4). Additionally, the limited availability of organ donors and the prolonged waiting list must be critically considered (5).

Among valve dysfunctions after HTx, tricuspid valve regurgitation (TR) is the most frequent. The etiology of TR after HTx is multifactorial, with endomyocardial biopsy (EMB) considered the main responsible (6), especially when performed multiple times (7). TR after HTx is most of the times asymptomatic and generally well tolerated, with medical therapy as first-line of treatment. However, on rare occasions TR may be disabling, even after therapy optimization, and surgical management may be required. In this case, the management is controversial and challenging for the heart failure team, as there are currently no clear guidelines to follow. The reported time from HTx to tricuspid valve replacement in these patients is estimated at 7.6 years, with >80% patients receiving a bioprosthesis (8). As a matter of fact, tricuspid valve replacement with bioprosthesis is considered the best choice to allow repeated EMB, nowadays the established method for monitoring allograft rejection. Almost 74% were alive at mean follow-up of 3.2 years. Surgical TR management after medical therapy failure has shown an improvement quality of life and lower mortality rates (8).

Left-sided heart valves severe dysfunction after HTx are less commonly described in the literature and usually reported as case reports or series (9). Mitral valve regurgitation seems to be the prevalent disorder. The primary etiologies are annular dilation or degeneration of the valvular structure. Among surgical options, mitral valve replacement is often preferred, primarily to minimize cardiopulmonary bypass duration and to eliminate the need for re-clamping in the event of a mitral valve repair failure (10). Anatomical distortions following HTx has to be taken into consideration in case of minimally invasive approaches (11). The current literature report a mean time of 6.73 years (range: 42 days to 21 years) from HTx to mitral valve surgery (9). Mechanical valves were mostly implanted (62.5%) and 65.6% of patients were alive at a mean follow-up of 2.78 years (range: 10 days to 14.4 years).

Severe degenerative aortic valve stenosis and endocarditis are the principal etiologies for aortic valve replacement after HTx. It is estimated that aortic valve surgery is performed at a mean of 4.88 years (range: 1 month to 11.4 years) after HTx, mostly with mechanical valves (62.5%) (9). More than 86% of patients were reported still alive at a mean follow-up of 1.53 years (range: 6 days to 7.7 years). Besides, considering that more marginal donors with possible preexisting pathologies or anatomical variations are selected, bicuspid aortic valve degenerations are more frequently encountered (9). This is in response of a global donor organ shortage trying to reduce the waiting list. Nevertheless, physicians and surgeons should always remember that not all marginal donors will have ideal outcomes.

Historically, conditions like aortic stenosis, mitral and tricuspid regurgitations were addressed through standard open surgical interventions. Over the past two decades, transcatheter procedures, including both replacement and repair, have become more accessible and widely adopted for treating post-HTx valvulopathies (12). This aspect is particularly important when considering patients with limited life expectancy, for whom quality of life holds greater value than long-term survival. Transcatheter valve procedures are being increasingly utilized to stabilize the valvular condition and delay re-transplantation (when still possible). While the number of reported cases involving percutaneous valve treatments in transplant recipients is currently limited, it is anticipated that such procedures will gain prominence soon, serving as a definitive treatment for high-risk patients or as necessary interventions to prolong allograft life before cardiac re-transplantation, and alleviate symptoms.

In literature, surgical treatment of valvular pathologies after HTx remains controversial, mainly due to the limited knowledge of outcomes, but the shortage of donor organs and/or the acceptance of marginal donors will lead to an increase patients needing reoperation to improve allograft function in transplanted hearts. To date, guidelines on cardiac surgery after HTx are still lacking, necessitating a case-by-case treatment assessment. Re-transplantation indications must be weighed against alternative therapeutic approaches like late cardiac surgery or transcatheter procedures on the transplant heart. The general principles guiding indications for cardiac surgery appear applicable while awaiting more robust evidence in transplanted patients (8,9,12). Surgical correction of valvular lesions following HTx is considered reasonable, provided special attention is given to patients with ventricular dysfunction and/or pulmonary hypertension, as they are at higher risk for right ventricular failure. Before proceeding with cardiac reoperation, it is essential to rule out underlying conditions such as cardiac allograft vasculopathy (CAV) or acute rejection (13).

CAV stands as the principal determinant of long-term allograft fate, responsible for approximately one in eight deaths among HTx survivors beyond the first year (14). Its pathobiology is fundamentally distinct from native atherosclerosis: rather than focal lipid-driven plaque formation, CAV produces a concentric, diffuse fibroproliferative thickening of the intima driven by a combination of chronic immune activation, antibody-mediated injury, and traditional cardiovascular risk factors, ultimately affecting both epicardial conduits and the intramyocardial microvasculature (15). The burden of disease accumulates steadily over time, with prevalence estimates of 8%, 29%, and 47% at 1, 5, and 10 years post-transplantation, respectively (14).

Prompt recognition is complicated by a fundamental pathophysiological peculiarity of the transplanted heart: the absence of afferent reinnervation renders ischemia clinically silent in the vast majority of recipients, who will not experience angina regardless of the severity of luminal compromise (16,17). As a consequence, the first clinical sign of hemodynamically significant CAV is often a serious adverse event, like ventricular arrhythmia, acute heart failure, or sudden death, rather than a warning symptom. Routine surveillance by coronary angiography is therefore mandatory, supplemented in the early post-transplant years by intravascular ultrasound (IVUS), which detects subclinical intimal thickening well before angiographically visible stenoses develop (15,16).

Once established, CAV offers limited therapeutic options. The diffuse nature of the disease confines revascularization to a small proportion of patients in whom focal, proximal lesions coincide with suitable vessel caliber (15). In this anatomically favorable subset, percutaneous coronary intervention (PCI) with drug-eluting stents is the preferred approach, supported by comparisons showing superior procedural outcomes and patient survival relative to surgical revascularization (15,16). Even so, restenosis after PCI in CAV consistently exceeds rates observed in native coronary artery disease, and the problem is markedly amplified in small vessels: in-stent restenosis rates approaching 39% have been reported for target vessels of 2.5 mm or less (18). Coronary artery bypass grafting (CABG) occupies a narrow but real role for patients with left main or multi-vessel disease beyond the reach of percutaneous techniques. A meta-analysis of 1,520 patients found lower need for repeat intervention after CABG compared to PCI, though at the cost of higher overall mortality, a finding likely reflecting the more advanced disease burden in patients selected for surgery rather than a true treatment effect (19). The CASH multicenter registry confirmed the rarity of surgical coronary revascularization after HTx, with only 16 of 110 operated patients undergoing CABG, predominantly for advanced CAV at a median of nearly nine years from transplantation (13). For diffuse end-stage disease, re-transplantation remains the sole option with potential for meaningful allograft renewal, but donor scarcity, reduced long-term survival relative to the primary procedure, and a substantially higher rate of CAV recurrence in the new allograft all constrain its application (20).

In general, cardiac surgery in post-HTx patients carries greater risks compared to the standard surgical population. As these procedures are inherently reinterventions, they are associated with higher rates of intraoperative and postoperative bleeding. Additionally, long-term immunosuppression in these patients increases their vulnerability to complications such as renal failure, infections, and impaired wound healing.

The boundaries are continuously being pushed to improve the patient’s functional status and to decrease re-transplantation. Managing valvular issues in HTx recipients still raises important questions, particularly in patients with marginal donors or higher risks of ventricular dysfunction or rejection (21). Stronger evidence is needed to explore whether more aggressive surgical interventions or preemptive annuloplasty at the time of transplant could improve outcomes. The role of transcatheter interventions in these patients is also uncertain, including their durability, complications, and potential as a bridge to re-transplantation or destination therapy. Stronger evidence should be gathered on patient selection, feasibility, and long-term clinical outcomes, supported by prospective studies or registry data. While transcatheter therapies have been transformative for native hearts, their role in HTx patients requires further investigation before they can become standard therapy.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Visualized Surgery. The article has undergone external peer review.

Peer Review File: Available at https://jovs.amegroups.com/article/view/10.21037/jovs-2026-0032/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://jovs.amegroups.com/article/view/10.21037/jovs-2026-0032/coif). M.B. serves as an unpaid editorial board member of Journal of Visualized Surgery from September 2026 to December 2028. The other author has no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement:This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See:https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2022;145:e895-e1032. [Crossref] [PubMed]
2. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC. Rev Esp Cardiol (Engl Ed) 2022;75:523. [Crossref] [PubMed]
3. Khush KK, Cherikh WS, Chambers DC, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-fifth Adult Heart Transplantation Report-2018; Focus Theme: Multiorgan Transplantation. J Heart Lung Transplant 2018;37:1155-68. [Crossref] [PubMed]
4. Batra J, DeFilippis EM, Clerkin K, et al. A change of heart: Characteristics and outcomes of multiple cardiac retransplant recipients. Clin Transplant 2024;38:e15214. [Crossref] [PubMed]
5. Barghash MH, Pinney SP. Heart Retransplantation: Candidacy, Outcomes, and Management. Curr Transplant Rep 2020;7:12-7. [Crossref] [PubMed]
6. Alyaydin E, Gotschy A, Parianos D, et al. Tricuspid regurgitation after heart transplantation: where innovation and intervention are in hibernation. Heart Fail Rev 2025;30:619-25. [Crossref] [PubMed]
7. Nguyen V, Cantarovich M, Cecere R, et al. Tricuspid regurgitation after cardiac transplantation: how many biopsies are too many?. J Heart Lung Transplant 2005;24:S227-31. [Crossref] [PubMed]
8. Cuko B, Baudo M, Busuttil O, et al. Outcomes of tricuspid valve prostheses after heart transplantation: a systematic review. Heart Fail Rev 2024;29:219-26. [Crossref] [PubMed]
9. Cuko B, Baudo M, Busuttil O, et al. Outcomes of left-sided heart valve surgery after heart transplantation: a systematic review. Heart Fail Rev 2024;29:227-34. [Crossref] [PubMed]
10. Bouma W, Brügemann J, Hamer IJ, et al. Mitral valve repair and redo repair for mitral regurgitation in a heart transplant recipient. J Cardiothorac Surg 2012;7:100. [Crossref] [PubMed]
11. van der Merwe J, Casselman F, Stockman B, et al. Endoscopic Port Access Surgery for Late Orthotopic Cardiac Transplantation Atrioventricular Valve Disease. J Heart Valve Dis 2017;26:124-9. [PubMed]
12. Cuko B, Baudo M, Busuttil O, et al. Transcatheter valvular interventions after heart transplantation: A systematic review. Trends Cardiovasc Med 2024;34:362-8. [Crossref] [PubMed]
13. Gökler J, Aliabadi-Zuckermann AZ, Kaider A, et al. Indications, Complications, and Outcomes of Cardiac Surgery After Heart Transplantation: Results From the Cash Study. Front Cardiovasc Med 2022;10:879612. [Crossref] [PubMed]
14. Khush KK, Hsich E, Potena L, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-eighth adult heart transplantation report - 2021; Focus on recipient characteristics. J Heart Lung Transplant 2021;40:1035-49. [Crossref] [PubMed]
15. Kamel MA, Scalia IG, Badr AT, et al. Cardiac Allograft Vasculopathy: Challenges and Advances in Invasive and Non-Invasive Diagnostic Modalities. J Cardiovasc Dev Dis 2024;11:95. [Crossref] [PubMed]
16. Pighi M, Gratta A, Marin F, et al. "Cardiac allograft vasculopathy: Pathogenesis, diagnosis and therapy". Transplant Rev (Orlando) 2020;34:100569. [Crossref] [PubMed]
17. Manrique Antón R, Pascual Izco M, Bastarrika G, et al. Non-Invasive Myocardial Work Identifies Patients with Obstructive Coronary Lesions After Orthotopic Heart Transplantation. Diagnostics (Basel) 2025;15:1352. [Crossref] [PubMed]
18. Elhage Hassan M, Khawaja M, Jaber WA, et al. Restenosis rates for drug-eluting stents used in treating small vessel cardiac allograft vasculopathy after orthotopic heart transplantation. Cardiovasc Revasc Med 2025;73:64-9. [Crossref] [PubMed]
19. Luc JGY, Choi JH, Rizvi SA, et al. Percutaneous coronary intervention versus coronary artery bypass grafting in heart transplant recipients with coronary allograft vasculopathy: a systematic review and meta-analysis of 1,520 patients. Ann Cardiothorac Surg 2018;7:19-30. [Crossref] [PubMed]
20. Alyaydin E, Flammer AJ. In the Twilight of Evidence: Is Bypass Surgery Still on the Table for Cardiac Allograft Vasculopathy?. J Clin Med 2024;14:132. [Crossref] [PubMed]
21. Rezkalla JA, Eleid MF. Editorial commentary: Extending the success of transcatheter valvular interventions to transplanted hearts. Trends Cardiovasc Med 2024;34:369-70. [Crossref] [PubMed]