Over the last 11 years, heart transplantation (HTx) from donation after circulatory death (DCD) donors has been widely adopted with transplant programs reporting survival outcomes comparable to those of contemporary heart transplants from donation after brain death (DBD) donors.1 In some programs, DCD donors account for 40% of the program’s HTx activity. The major difference between hearts retrieved from DCD and DBD donors is that the DCD heart is subjected to a period of obligatory warm ischemia during withdrawal of life support (WLS). In addition, hypoxia during WLS triggers an acute increase in pulmonary vascular resistance placing an additional load on the ischemic right ventricle.2 Following circulatory arrest, there is marked distension of the right sided heart chambers.2 Two major retrieval modalities have been developed for procurement of hearts from DCD donors: direct procurement followed by normothermic machine perfusion (DPP) and normothermic regional perfusion (NRP) which may be followed by static cold storage (either ice or temperature controlled) or by machine perfusion of the donor heart. The major advantage of NRP is that it effectively converts a DCD donor to a DBD donor enabling in situ viability assessment of the donor heart after death has been declared. Once viability of the DCD heart has been established during NRP, the procurement and transport of the heart can be performed similarly to that of a DBD donor usually without the need for machine perfusion. NRP has additional advantages including applicability to infant donors where donor heart size restricts use of normothermic machine perfusion, improved preservation of abdominal organs and reduced costs. The main concern causing restricted uptake of NRP in many jurisdictions has been the ethical concern that restarting the circulation in a patient who has been declared dead based on circulatory criteria conflicts with the ‘dead donor rule’. To date, the majority of hearts transplanted from DCD donors have been retrieved using the DPP protocol utilising the Transmedics Organ Care System, which is currently the only device approved for normothermic machine perfusion.1,3 After rapid collection of donor blood for use in the machine perfusate and flushing of the heart with a preservation flush solution, the heart is excised and mounted on the machine perfusion device in a Langendorff configuration. In this configuration, blood is delivered retrogradely down the aorta against a closed aortic valve. The heart is perfused antegradely via the coronary circulation with the coronary venous drainage to the right atrium. The right ventricle ejects the coronary perfusate to the pulmonary artery which is connected to the reservoir via a return cannula. In this configuration, the left ventricle is beating but not performing any external work whereas the right ventricle is both beating and working. There is both an advantage and disadvantage to this configuration – the advantage being that the left ventricle is being rested during transport on the device, the disadvantage being that it is not possible to directly assess the function of the left ventricle during DPP. Assessment of the viability and functional recovery of the DCD heart during DPP has been based on several functional parameters including recovery of an intrinsic cardiac rhythm, coronary blood flow and coronary perfusion pressure and metabolic parameters most notably serial lactate measurements in the coronary perfusate using a portable point-of-care assay. With regard to the latter, a declining lactate level with evidence of myocardial lactate extraction has been recommended as evidence of myocardial viability. The use of lactate as an indicator of viability theoretically makes sense given that upon ischemic injury, cells switch from aerobic to anaerobic metabolism causing a rise in lactate levels. Upon reperfusion and restoration of aerobic metabolism, reduced lactate levels over time should reflect the improved heart function. However, the reliability of serial lactate measurements has been questioned with reports of DCD hearts showing excellent functional recovery despite an unfavourable lactate trend.4,5 Hence there is a need for additional functional or metabolic measures which will help to distinguish between viable and non-viable DCD hearts. A recent single-centre retrospective study analysed the blood gas samples from 26 DCD hearts during normothermic machine perfusion and found an inverse correlation between arteriovenous PO2 differential and lactate measurements,6 suggesting that analysis of 2 (or more) measurements combined can be useful for determining heart viability and transplant suitability. In this issue of the journal, Saemann et. al. in press this issue7 describe a novel technique to predict ventricular contractility of directly procured DCD hearts during ex situ normothermic machine perfusion (ESMP). The authors implanted a laser Doppler perfusion needle probe into the anterior left ventricular (LV) wall of canine DCD hearts to assess the coronary microcirculation during ESMP, then transplanted the DCD heart into a recipient animal. A major strength of this study is that all hearts were transplanted orthotopically and all were weaned from bypass to enable direct measurement of LV contractility using a conductance catheter to measure the LV end-systolic pressure volume relationship. Even though all animals were subjected to the same withdrawal of life support protocol with a 10 minute asystolic warm ischemic time (aWIT) there was a marked variation in the recovery of LV contractility post heart transplant. This is surprising given the short aWIT time. Nonetheless, the authors were able to show a close correlation between the first-to-last or second-to-last shift in laser Doppler perfusion during ESMP combined with coronary venous lactate concentration and LV contractility post heart transplant. While this is a promising result further research and validation is needed. Orthotopic heart transplants with a longer aWIT time would be a good next step. Also, the practical feasibility of applying this technique in clinical transplantation should be addressed – ie, will the results of the shift in laser Doppler perfusion be available at the time of measurement similar to a ‘point-of-care’ assay? Finally, with the emergence of hypothermic oxygenated perfusion of human DCD hearts as an alternative to normothermic machine perfusion,8,9 it would be valuable to determine whether laser Doppler perfusion was also able to predict functional recovery of DCD hearts during hypothermic oxygenated perfusion.
Villanueva et al. (Tue,) studied this question.