Organ perfusion systems a boon to heart and lung transplants

Aug. 11, 2021

Heart and lung transplant specialists in at Mayo Clinic's campus in Jacksonville, Florida, are innovating with technology to serve the needs of patients requiring transplant. One technological focus — heart and lung perfusion systems — offers significant benefits for organ recipients.

Heart in a box

Mayo Clinic heart transplant specialists are studying a new perfusion system often called "heart in a box" to better sustain donor hearts for transplant. This system preserves a heart while it is beating, extending the time between retrieval and transplant by several hours. With the standard heart preservation technique, this window has ideally been only about three to five hours. In addition, the new system has the potential to widen the donor pool by supporting the novel use of donation after circulatory death (DCD) hearts by reviving and supporting the recovery of nonbeating hearts.

Heart perfusion system benefits

When transplant specialists place a retrieved donor heart in the machine, it perfuses the organ with warm, oxygenated blood, reviving the heart from nonbeating to beating status. The system's measurements also give transplant professionals an opportunity to confirm the heart's function before accepting it for transplant.

"The perfusion system analyzes the heart's hemodynamic parameters, monitoring every 15 to 30 minutes as if it were a patient in the ICU," says Si M. Pham, M.D., chair of Cardiothoracic Surgery at Mayo Clinic in Florida. "We have to resuscitate the heart until it meets strict transplant criteria."

In most heart donors who meet brain-death criteria, the heart is still beating and working well. However, DCD hearts have stopped and need to be revived and evaluated before they can be used for transplant. Beyond increasing organ availability by facilitating DCD heart donations, the perfusion system offers the following advantages:

  • Allows a heart to travel distances — even by air — up to 1,000 miles or six hours
  • Enables use of older hearts and hearts that previously would have been unusable

The heart perfusion system not only helps shorten the heart waitlist by increasing the donor pool but also translates to better outcomes and fewer patient deaths while awaiting a heart, says Parag C. Patel, M.D., a transplant cardiologist at Mayo Clinic's Florida campus.

"We're not just giving them a heart earlier, but giving them a better chance," says Dr. Patel. "Utilization of DCD organs through a heart perfusion device also opens up opportunities for earlier transplantation in the sickest patients by reducing competition for hearts through the larger donor pool."

While some medical centers hesitate to use extended-criteria hearts and have concerns about ischemia time, Dr. Pham is excited about the possibility of more available hearts through perfusion, especially in the case of DCD organs. He says potential DCD organs unfortunately aren't uncommon, as hospitals see many patients with severe damage incompatible with life. Until recently, physicians have considered abdominal organs for transplant rather than heart transplant in these cases.

"So far, we have evaluated eight DCD organs and were able to transplant six (85%) of them successfully," says Dr. Pham. "In the past, these six organs would not have been used. So perfusion has the potential not only to increase donor availability but also to have recipients in better condition."

Heart perfusion costs

Dr. Pham explains that using a heart perfusion system for transplant requires not only considerable surgical skill but significant logistical support as well. Perfusion systems also increase heart transplant costs, as they require additional personnel, says Dr. Patel. "It will hurt a medical center's bottom line," Dr. Patel explains. "But if it shortens patients' transplant wait times and reduces pretransplant hospital length of stay, that will make the cost go down."

Future for heart perfusion systems

Dr. Patel doesn't envision perfusion system use in all heart transplants. It's unnecessary in local surgery where organ transfer occurs more rapidly or for younger donors.

Dr. Pham expects the FDA to approve the heart in a box system this year for DCD hearts. Currently, a clinical trial is studying this system for DCD hearts.

Dr. Patel says Mayo Clinic in Florida uses heart perfusion for about one case a month. The center performs 50 heart transplants yearly, and he foresees perfusion system use in 20% to 25% of future cases.

Though heart perfusion doesn't offer organ restoration presently, that's the long-range goal. Right now, Dr. Patel says heart perfusion provides pseudo-restoration, yet only with traditionally transplant-eligible hearts. The heart in a box system enables extended-criteria heart use, enabling more patients to receive heart transplants.

Lung perfusion systems

For lung transplantation, Mayo Clinic specialists also envision perfusion benefits through ex vivo lung perfusion (EVLP), which assesses extended-criteria lungs. Examples include lungs with abnormal X-rays, decreased oxygen levels or elevated airway secretions.

Lung perfusion system function, advantages

The primary purpose of lung perfusion systems is to allow evaluation of lungs in isolation, explains Jorge M. Mallea, M.D., a transplant pulmonologist at Mayo Clinic's Florida campus.

Two lung perfusion systems are being used at Mayo Clinic in Florida: One is FDA approved and a second is available through clinical trial only. Either can assess extended-criteria lungs or preserve a lung during unforeseen transplant delays.

Dr. Mallea explains that EVLP improves lung function by:

  • Drying lungs with excess fluid
  • Removing excess respiratory secretions and mucus through bronchoscopy
  • Expanding poorly inflating lungs (atelectasis)

"In the future, the goal is to provide medications or cell therapies during EVLP — not just assess lung function, but improve lung quality," says Dr. Mallea.

Though many lung transplants are bilateral, specialists use EVLP for one or two lungs, contributing to an increased donor pool and a greater number of transplant-available lungs. EVLP allows lungs previously only considered suitable for discard to be considered for transplant.

Patients who receive EVLP lungs and those who receive nonperfused lungs experience similar transplant outcomes, says Dr. Mallea.

Dedicated perfusion facilities

Mayo Clinic also has pursued dedicated organ perfusion facility development to allow lung perfusion technology to be accessible to other transplant centers in the southeastern United States. Dedicated perfusion facilities could function essentially like blood banks, but for solid organ perfusion. Mayo Clinic collaborated with Lung Bioengineering, a subsidiary of United Therapeutics, to create such a facility in the Discovery and Innovation Building on its Florida campus. This building includes three EVLP procedure rooms staffed by specialized personnel trained in lung perfusion as well as a good manufacturing practice facility for cell manufacturing and the Mayo Clinic Innovation Exchange.

Dr. Mallea says that dedicated perfusion centers can improve efficiencies and possibly be more cost-effective for transplant centers of different sizes. Transplant centers would not need to dedicate an operating room or assign personnel specifically for organ perfusion if they have access to a dedicated EVLP facility.

Future goals for this lung perfusion location at Mayo Clinic include repairing lungs that are currently EVLP unsuitable, such as those with motor vehicle crash contusions or with pneumonia caused by gastric content aspiration. Therapies that in the future can be applied to lungs in the EVLP circuit include gene editing, stem cell treatments and cell-derived therapies, among others.

"EVLP is the ideal platform to assess therapies and technologies aimed at regenerating damaged lungs," says Dr. Mallea.

Perspective on heart and lung perfusion systems

Drs. Pham, Patel and Mallea all foresee strong future potential for organ perfusion systems.

"Bottom line, we are very productive in adapting new technology and policy to get the best for our patients — for them not only to have a transplant but to do well with it," says Dr. Pham. "Early adaptation in tech allows us to be a high-volume transplant center."

Dr. Pham adds that perfusion will save lives; he anticipates that his heart transplant team will perform 10 to 12 additional heart transplants annually because of perfusion.

"This is one of the most exciting things in heart transplant since it started in 1967," Dr. Pham says. Dr. Mallea shares his enthusiasm about the use of this technology in the lung transplant field as well.

Disclosure: Mayo Clinic has an agreement in place with Lung Bioengineering to provide organ perfusion services.