Combined heart-lung transplant (HTLx) remains the most durable treatment for end-stage heart and lung failure. Many patients are unable to receive combined organs due to availability and allocation policies prioritizing separate heart or lung transplantation. Over the last 5 years an average of 45 HTLxs have been performed per year in the United States. However, only 50% of the listed patients were transplanted.1 Pasupneti et al. reported in 2017 that median survival after combined heart-lung transplant is lower than either heart transplant or bilateral lung transplant (3.3 vs. 7.1 and 10.4, respectively). However, they note that “conditional survival,” defined as survival after the first year, is similar in HTLx and bilateral lung transplant (10.0 vs. 9.7 years, respectively).2 Recently, donation after circulatory death (DCD) utilizing normothermic regional perfusion (NRP) has been utilized for heart allografts with excellent results.3,4 DCD lung transplantation utilizing NRP is beginning to be reported on with good results.5

In 2019 the first DCD HLTx was performed in the U.K. utilizing off-label modifications to an ex situ portable lung device (OCS Lung, TransMedics, North Andover, MA).6 A multi-institutional clinical trial was recently published confirming the safety and effectiveness of DCD heart transplant using TransMedics OCS Heart.7 Later in 2019, a HTLx utilizing NRP was performed in the US co-locating the organ donor and recipient to the transplant center. Severe lung primary graft dysfunction occurred, however, the recipient subsequently recovered. We present a successful HTLx after DCD using a mobile NRP paradigm.

Case Presentation

A 62 year-old man, blood type A positive, with familial dilated cardiomyopathy and pulmonary fibrosis was listed for HTLx as status 4 and LAS score 41.3. His oxygen requirement was 6L at rest. He had heart failure with a left ventricular ejection fraction of 23% and New York Heart Association class IIIB heart failure. His right heart catheterization 5 months prior to transplant showed a central venous pressure of 5 mmHg, a pulmonary arterial pressure of 29/10 mmHg, and a pulmonary capillary wedge pressure of 9 mmHg. His pulmonary vascular resistance was 8 woods units. Two months before transplant the recipient contracted COVID-19 and had a significant decline in his pulmonary function requiring hospitalization. At the time of transplant, he had been listed at our center 17 days. The donor was a 24 year-old man who suffered head trauma. Research data collection and DCD donation were consented for by the family. The echocardiogram was within normal limits. His PaO2/FiO2 ratio was 489 mmHg on a PEEP of 5 cmH2O. The donor was 633 km away from the transplant center.

The heart-lung bloc was offered at sequence #5. Our organ recovery team traveled with a portable NRP system (Spectrum, Gloucester, UK, and Terumo, Ann Arbor, MI) (Figure 1A). The circuit allows for cardiopulmonary bypass with a reservoir. 400 U/kg Intravenous heparin was given before withdrawal and the donor arrested 12 minutes after extubating. The donor was declared deceased by the donor hospital staff per their protocol. Following a 5 minute no touch period, the chest was opened via sternotomy, the arch vessels individually clamped, and the donor was cannulated in the ascending aorta and the right atrium (Figure 1B). Normothermic regional perfusion was initiated five minutes after incision. The donor was reintubated and ventilated. We weaned from NRP after 40 minutes allowing the donor heart to independently perfuse the body. The PaO2/FiO2 ratio was 473 mmHg. Bilateral ventricular function was excellent by visual inspection. The cross clamp was applied and the organs were procured in the standard fashion (Figure 2A) including heart and lung bloc, liver, and kidneys. Total NRP time was 68 minutes and the organ block was transported via jet aircraft using cold storage in Perfadex (EX; XVIVO, Sweden) crystalloid solution within an Igloo (TX) cooler with ice (Figure 2B).

Figure 1.:

NRP procurement technologies. A: Mayo Clinic mobile normothermic regional perfusion system (Spectrum, Gloucester, UK and Terumo, Ann Arbor, MI). B: Heart-Lung donor cannulated for normothermic regional perfusion.

Figure 2.:

NRP storage and transport technologies. A: Heart-Lung block following procurement. B: Cooler used for allograft transport (Igloo; TX).

The HTLx was performed via sternotomy. The lungs were placed through pericardial incisions into the pleural space made beneath the phrenic nerves bilaterally. The anastomoses were completed in the order of trachea, aorta, inferior vena cava, and finally superior vena cava. The allograft ischemic time was 222 minutes and cardiopulmonary bypass time for the recipient was 263 minutes. The chest was closed and there was no primary graft dysfunction (Figure 3, post-operative day 2 chest X-Ray). The patient was extubated 5 days posttransplant; the delay in extubation was due to postoperative delirium. He was transferred from the ICU 10 days posttransplant. The postoperative course was complicated by acute kidney injury requiring temporary renal replacement. He was discharged on Post-operative Day (POD) 32 in good condition.

Figure 3.:

POD 2 chest x-ray.

Comment

Normothermic regional perfusion may provide several benefits in DCD transplantation. While it does not extend our reach to procurement sites beyond safe distance for cold storage as TransMedics OCS has done for heart,8 It allows successful heart transplantation from DCD donors with an in situ assessment of function. Supportive evidence for its safe use in lung transplantation is growing. There have been ethical concerns regarding NRP; however, we consider the current protocol squarely within ethical standards. Declaration of death is performed by the donor institution without recipient center involvement and there is either a 2 or 5 minute no touch period to allow for autoresuscitation depending on donor center protocol. Last, as this case has shown, there is a potential to improve multi-organ donor utilization and quality from our DCD donors applying portable NRP technology as there are no currently approved ex situ systems for heart-lung organ blocks.

References 1. Organ Procurement and Transplantation Network: National data. 2022. 2. Pasupneti S, Dhillon G, Reitz B, Khush K: Combined heart lung transplantation: An Updated review of the current literature. Transplantation. 101: 2297–2302, 2017. 3. Kwon JH, Ghannam AD, Shorbaji K, et al.: Early outcomes of heart transplantation using donation after circulatory death donors in the United States. Circ Heart Fail. 15: 122.009844, 2022. 4. Smith DE, Kon ZN, Carillo JA, et al.: Early experience with donation after circulatory death heart transplantation using normothermic regional perfusion in the United States. J Thorac Cardiovasc Surg. 164: 557–568.e1, 2022. 5. Zhou AL, Ruck JM, Casillan AJ, et al.: Early United States experience with lung donation after circulatory death using thoracoabdominal normothermic regional perfusion. J Heart Lung Transplant. 42: 693–696, 2023. 6. Messer S, Abu-Omar Y, Large SR, et al.: Combined heart–lung transplantation from a donation after circulatory death donor. J Heart Lung Transplant. 39: 1366–1371, 2020. 7. Schroder JN, Patel CB, DeVore AD, et al.: Transplantation Outcomes with Donor Hearts after Circulatory Death. N Engl J Med. 388: 2121–2131, 2023. 8. Verzelloni Sef A, Sef D, Garcia Saez D, et al.: Heart transplantation in adult congenital heart disease with the organ care system use: A 4-year single-center experience. ASAIO J. 67: 862–868, 2021.