A paradigm shift occurred for the treatment of irreversible end-stage lung disease when the Toronto lung transplant team achieved long-term success with a single lung transplantation (SLT).1 The first bilateral lung transplant was reported in 1988, followed shortly thereafter by the introduction of the bilateral sequential lung transplant technique (BLT).2 SLT and BLT have ever since existed as possible therapeutic options to choose between. In the absence of randomized controlled trials comparing SLT and BLT, a series of retrospective cohort studies and analyses of lung transplant registry databases provide some themes:
- - Compared with SLT, BLT is generally associated with longer posttransplant survival.3
- - When attempting to control for possible SLT versus BLT candidate selection biases by limiting the study population to only candidates who were listed for both options, there is no appreciable survival difference between procedure.4
- - In candidates with significant secondary pulmonary hypertension (SPH), SLT is associated with worse survival.3
In this edition of Transplantation, Sunagawa et al5 report on the Temple University experience with SLT in patients with severe SPH. This retrospective single-center cohort study included 318 SLT recipients who were transplanted between January 2017 and December 2019. It deserves an emphasis that most of the patients who underwent SLT in this cohort were older and did not have severe SPH at the time of listing but developed it by the time they underwent transplantation. Swan-Ganz-catheter data from the time of the lung transplant operation of the SLT candidates were used to stratify recipients into 3 groups based on mean pulmonary artery pressures (mPAP):
- A. No SPH (mPAP <25, n = 42)
- B. Mild SPH (mPAP 25–40 mm Hg, n = 219)
- C. Severe SPH (mPAP >40 mm Hg, n = 59)
The authors report that the severe SPH group required more intraoperative cardiopulmonary support (severe SPH 37.3% versus mild SPH 10.3% versus no SPH 4.7%, P < 0.05); however, there were no significant differences in most major postoperative outcomes, including the duration of postoperative mechanical ventilation or the incidence of severe primary graft dysfunction. Furthermore, survival 1 y posttransplant was not significantly different among the groups (severe SPH 93.2% versus mild SPH 89.4% versus no SPH 92.9%, P = 0.58).
Before concluding that SLT (with appropriate intraoperative mechanical circulatory support) is a comparable option for candidates with severe SPH, there are several challenges that need to be carefully addressed.
In general, the type of operation (SLT versus BLT) is planned based on data during the lung transplant evaluation. The stratification of the study cohort here, however, occurred based on mPAP at the time of the operation. It is notable that, at the time of listing, the stratification of patients would have been quite different: the mPAPs at the time of listing were in group (A) 20.9 ± 5.1 mm Hg, (B) 23.3 ± 7.1 mm Hg, and (C) 26.9 ± 7.4 mm Hg, respectively. This suggests that, at time of listing, the study cohort on average had no or only mild SPH. This also highlights that, during the listing time of (A) 165.4, (B) 168.7, and (C) 136.7 d, there was a substantial increase in mPAP in groups B and C.
Furthermore, assessment of right ventricular (RV) function is a critical element in the procedure planning process for both type of procedure and need for intraoperative support. In this study at the time of listing, right atrial pressures and cardiac indices were within the normal range in all cohorts, suggesting preserved RV function at that time. Although not reported by objective data, a key component in the determination of the procedural plan was the intraoperative transesophageal echocardiographic assessment of RV function. In future studies, it will be critical to determine RV function-based risk stratification tools that allow for a generalizable approach to procedural planning.
In addition, clarifying comprehensive recipient and donor risk factors to allow for optimized candidate selection will be critical. Advances in extracorporeal support strategies, procedural approaches, donor to recipient matching practices (awareness of the risks associated with undersized allografts, especially in the context of pulmonary hypertension). and improvements of perioperative management strategies all could lead to a resurgence of SLT.6,7 In addition to short-term outcomes (perioperative morbidity and mortality, 1-y survival), SLT will also have to prove itself in terms of longer-term survival and patient-related outcome measures.
In summary, Sunagawa et al5 from the Temple University lung transplant program should be commended for their excellence, expertise, and efforts to expand the role of SLT in the context of SPH. If these results are confirmed in future studies, the possibly expanded role of SLT could be a step in the right direction to achieve the OPTN goals of increasing the number of transplants, providing equity in access to transplants and improving waitlisted patient and transplant recipient outcomes.8
1. Toronto Lung Transplant Group. Unilateral lung transplantation for pulmonary fibrosis. N Engl J Med. 1986;314:1140–1145.
2. Kaiser LR, Pasque MK, Trulock EP, et al. Bilateral sequential lung transplantation: the procedure of choice for double-lung replacement. Ann Thorac Surg. 1991;52:438–445; discussion 445.
3. Villavicencio MA, Axtell AL, Osho A, et al. Single- versus double-lung transplantation in pulmonary fibrosis: impact of age and pulmonary hypertension. Ann Thorac Surg. 2018;106:856–863.
4. Ranganath NK, Malas J, Phillips KG, et al. Single and double lung transplantation have equivalent survival for idiopathic pulmonary fibrosis. Ann Thorac Surg. 2020;109:211–217.
5. Sunagawa et al. Single lung transplant remains a viable option for patients with severe secondary pulmonary hypertension. Transplantation. [Epub ahead of print. June 6, 2022].doi:10.1097/TP.0000000000004191
6. Eberlein M, Reed RM, Bolukbas S, et al. Lung size mismatch and survival after single and bilateral lung transplantation. Ann Thorac Surg. 2013;96:457–463.
7. Eberlein M, Diehl E, Bolukbas S, et al. An oversized allograft is associated with improved survival after lung transplantation for idiopathic pulmonary arterial hypertension. J Heart Lung Transplant. 2013;32:1172–1178.
8. Organ Procurement and Transplantation Network. Vision and goals. U.S. Department of Health and Human Services. Available at https://optn.transplant.hrsa.gov/about/vision-goals/
. Accessed April 6, 2022.