Innovative Strategies for Organ Preservation in Heart Transplantation: Uniform Cooling Preservation and Ex-situ Normothermic Perfusion

Heart transplantation is the treatment of choice for patients with advanced heart failure. Despite improvement in long-term mechanical circulatory support, historically, the standard technique for the preservation of the donor heart is ice-cold storage. The heart is first flushed with preservation solution and then maintaining the same solution between two and eight degrees Celsius.

There are several limitations with this technique, temperature variation, and the remaining of an anaerobic metabolism that may cure lesions and lead to primary graft dysfunction. To avoid the temperature fluctuation, uniform cooling preservation has been developed and is increasingly used in Europe. Ex situ heart perfusion is the only commercially available device for transplantation of donor heart in normothermic perfusion states and has recently been demonstrated to expand the donor pool, especially for ECD and DCD allografts.

Early outcomes are comparable with the results of heart transplantation with brain dead, non-marginal donors. To avoid temperature fluctuations, uniform cooling preservation has been developed by Paragonic Society. Retrieve the sterile-nested canisters, the outer one protects the inner one, and place the inner one in a cup filled with ice.

A cold atmosphere is therefore created around the inner canister. Explant the donor heart conventionally with the longest possible ascending aorta to place the UCP-specific connector cannula high enough to preserve sufficient length for the aortic anastomosis. Choose the appropriate size for UCP aortic connector corresponding to the inner diameter of the ascending aorta.

Secure the aortic cannula into the aortic lumen with an external surgical loop. Connect to the inner canister cover to suspend the donor heart in the preservation solution. Tear the inner canister, by slowly flushing the preservation solution through a dedicated port.

Fluid will exit from a second port located on the cover. Fill the canister with solution up to the top, then close it with its dedicated cap. Ensure the donor heart is completely submerged in the preservation solution.

Then, place the inner canister inside the outer canister. Lock the outer canister with its dedicated cover. Place the outer canister in the shipper and start temperature monitoring.

Read the preservation temperature on the anterior screen of the shipper and on the mobile phone application. No temperature adjustment is possible during organ transportation using UCP. The organ care system developed by TransMedics is the only commercially available device validated for transportation of hearts in normothermic perfused state.

Cannulate the right atrium with a 32 French double-staged cannula. Connect a sterile heparinized bag, 10, 000 IU, to the right atrium cannula and collect 1, 200 to 1, 500 milliliters of blood. Allow 90 to 120 seconds for this process.

Place the heart in a sterile cup with four degrees Celsius saline solution. Place four pledgeted 4.0 monofilament sutures at the cardinal points of the distal ascending aorta. Choose the appropriate aortic cannula among the four sizes to fit with the diameter of the donor aorta.

Do not oversize the cannula. Secure the aortic cannula with an external cable tie to prevent accidental detachment of the heart from the connector during transport. Secure the malleable pulmonary cannula with a 4.0 monofilament running suture around the pulmonary trunk.

Create a purse-string suture with 4.0 monofilament on the left atrium to secure the left ventricular vent cannula. Insert the cannula into the left ventricle through the left atrium to allow de-airing during ESHP. Reduce the pump flow to 1, 000 milliliters per minute and remove the shunt between the aortic and venous lines before positioning the heart.

Place the heart upside down with posterior ventricular walls in front of the operator. De-air the ascending aorta and connect the aortic cannula to the aortic line. Perform a gentle cardiac massage until the heart is warmed up.

Deliver a 30 joules shock in case of ventricular fibrillation to obtain a sinus rhythm. Close the inferior vena cava with a 4.0 monofilament running suture. At this point, all the deoxygenated blood flowing from the coronary sinus goes into the right atrium and is ejected through the pulmonary artery since the right ventricle is beating.

De-air and connect the pulmonary cannula to the venous line. Place an epicardial pacing lead on the posterior wall of the right ventricle. Connect this lead to an external pacemaker and pace the heart at 80 beats per minute.

Once connected on the perfusion module, the isolated heart thus receives a warm 34 degrees Celsius oxygenated and nutrient-enriched perfusion. All consecutive heart transplantations performed in our institution between January 2020 and July 2023 were reviewed. Three groups were compared considering the approach for organ preservation:ice-cold storage, normothermic ex situ heart perfusion, and uniform cooling preservation using the uniform cooling preservation.

Primary graft dysfunction was defined by either left ventricular ejection fraction less than 30%and/or need for mechanical circulatory support within 24 hours after transplant, and/or need for urgent re-transplant during the hospital stay. Mean recipient age was 45.1 years without any difference between groups. Similarly, the indication for transplant and mean time on the waiting list was not statistically different between groups.

45%of patients were referred for transplant under mechanical circulatory support. Nine transplantations were combined with either Kidney 4 or Liver 5 transplant. Mean donor age was 42.7 years without difference between groups.

The median ischemic time for the donor heart was 195 minutes in ICS group, 113 minutes in ESHP group, and 247 minutes in UCP group. Postoperative high sensitivity cardiac troponin T was significantly lower in uniform cooling preservation group compared to ice-cold storage and ex situ heart perfusion groups. The rate of severe PGD was 27%in ICS group, 43%in ESHP group, and 14%in UCP group.

The need for temporary ECMO after transplant was observed in 42%of cases in ICS group, 71%in ESHP group, and 14%in UCP group. Median length of stay in intensive care unit was significantly lower in UCP group. Six-month survival rate was not different between groups.

Uniform cooling preservation and ex situ heart perfusion have opened a new era in heart transplantation. These approaches ensure optimized preservation of the donor heart to prevent several primary graft dysfunction. This is a major improvement in the current setting of donors with extended criteria and more challenging recipients refer to heart transplantation.

By minimizing cold-induced myocardial damages and ischemia-reperfusion injuries, this technology are already associated with improved clinical outcomes. The future of organ preservation will undoubtedly involve a multimodal strategy including these technologies.