New Strategies to Expand and Optimize Heart Donor Pool: Ex Vivo Heart Perfusion and Donation After Circulatory Death: A Review of Current Research and Future Trends : Anesthesia & Analgesia

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Cardiovascular and Thoracic Anesthesiology

New Strategies to Expand and Optimize Heart Donor Pool: Ex Vivo Heart Perfusion and Donation After Circulatory Death: A Review of Current Research and Future Trends

Beuth, Jodie MBBS*; Falter, Florian MD, PhD; Pinto Ribeiro, Roberto Vanin MD; Badiwala, Mitesh MD, PhD; Meineri, Massimiliano MD, FASE*,§

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Anesthesia & Analgesia 128(3):p 406-413, March 2019. | DOI: 10.1213/ANE.0000000000003919
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Due to the aging population, improved medical management of heart failure, and the use of mechanical circulatory support as a bridge to transplantation, the shortage of viable donor hearts (allografts) is far exceeding supply. Transplantation numbers have remained constant, with approximately 2400 heart transplants performed annually in the United States alone.1 An estimated 60% of potential allografts, however, are deemed ineligible for various reasons and are subsequently not transplanted.1,2 Over the past decade, significant efforts have been made to increase the donor pool and improve allograft allocation.3

Optimal allograft preservation involves reduction of ischemic time. Ischemia exceeding 4 hours significantly increases the risk of primary graft dysfunction (PGD), which is associated with 8% mortality at 30 days and increased mortality at 5 and 15 years posttransplantation.4–6 The standard preservation strategy consists of administering a single hypothermic flush of preservative solution into the aortic root on application of the cross-clamp and cold storage in ice.4 This method is deemed to slow down myocardial metabolic activity7 by enough to prevent significant ischemia–reperfusion injury in allografts from donors <40 years old.4

Over the past 10 years, the concept of ex vivo organ perfusion has been successfully applied to lungs, liver, and kidneys.8 This technique serves to limit cold ischemia time, as well as to allow for assessment and optimization of donor organs before transplantation.9 Ex vivo reconditioning of marginal donor lungs enabled an increase of the donor pool by 15%–30%.10,11 Recipient long-term survival, improvement in quality of life, and graft function are comparable with those having received donor lungs selected via conventional criteria.12 Ex vivo heart perfusion (EVHP) has recently been proven successful at minimizing allograft cold ischemia13–16 and at allowing graft assessment after donation after circulatory death (DCD).17

To date, there have been >200 heart transplants performed in 16 centers internationally using allografts preserved using this technique.18

The current review focuses on the recent trends to expand the heart donor pool and newer perfusion techniques to allow assessment and preservation of the allograft.


Allograft Selection

Successful cardiac transplantation involves careful selection and evaluation of the donor, the cardiac allograft, and allocation to an appropriate recipient.

The process of donor selection includes preliminary screening, establishing brain and/or cardiac death, and obtaining informed consent followed by final assessment of the allograft. The final decision on suitability for transplantation is at the discretion of the implanting surgeon and the explanting team after tactile and visual allograft inspection.19

A significant number of donor hearts are still rejected.20 The most common factors leading to exclusion are related to the donor’s age, female gender, cerebrovascular accidents, hypertension, diabetes mellitus, left ventricular ejection fraction <50%, wall motion abnormalities, palpable coronary artery disease, and elevated troponin.19–21

Marginal Cardiac Allograft

The criteria for assessment and acceptance of organs have evolved over time.22–24 “Extended” cardiac donor criteria have been introduced to expand the potential donor pool by broadening suitability characteristics (Table).20

Standard and Extended Cardiac Donor Criteria

In older donors or those with significant comorbidity,25–27 allograft selection may be controversial and often depends on a multidisciplinary team interaction and institutional preference and experience.28,29

Most centers are reluctant to transplant marginal allografts from suboptimal donors with extended acceptance criteria into nonurgent patients.21,30–32 However, acceptance of extended criteria allografts might be the only option for some patients with low priority on the heart transplant waiting list.33–35

Allograft Assessment

Assessment of organ suitability partially relies on biomarkers such as troponin, creatinine kinase-muscle/brain, and procalcitonin as potential indicators of myocardial damage. Their thresholds are based on published, but controversial data, which associates elevated troponin and procalcitonin levels with an increased incidence of PGD.4,31,36,37 In the context of brain death, troponin levels may be elevated as a result of brain demise and do not directly reflect myocardial damage.35,38 Applicability of these surrogate measures as independent predictors for adverse outcomes is currently debated.31 Functional assessment methods, such as echocardiography and electrocardiogram, thus remain the gold standard to determine eligibility.24

Cold Ischemia Time

Prolonged allograft ischemic time correlates with adverse recipient outcomes, such as impaired biventricular function, PGD, prolonged intensive care stay, and the need for prolonged inotropic or mechanical circulatory support.39,40 Current International Society for Heart and Lung Transplantation guidelines recommend ischemic time not to exceed 4 hours. The acceptable exception is young donor age and absence of cardiac disease or inotropic support before explant when paired with a suitable recipient without elevated pulmonary arterial pressures.41 An increase of cold ischemic time from 3 to 6 hours doubles the mortality risk at 1 year posttransplantation compared to a 50% reduction of predicted mortality at 1 year when ischemic time remains under 1 hour.42–45


DCD is considered when a patient has suffered irreversible, severe neurological injury but does not meet the criteria for certification of brainstem death.46 DCD criteria were established in 1992 by the University of Pittsburgh47 and define how a patient unlikely to survive after withdrawal of life-sustaining treatment may be regarded as a potential organ donor.46

The Maastricht criteria (modified in 2011) universally define categories suitable for DCD48–50 as follows:

  • I. Deceased before hospital arrival
  • II. Unsuccessful resuscitation
  • III. Cardiac death after withdrawal of life-sustaining measures
  • IV. Cardiac death after brain death
  • V. Unexpected death of an in-hospital patient after unsuccessful resuscitation

Category III is the most commonly used source of DCD donors because it permits a “controlled” warm ischemic time. Category IV applies to a small group of donors in whom formal brainstem testing is not feasible due to hemodynamic or respiratory instability. “Uncontrolled” DCD categories (categories, I, II, and V) are characterized by a long or unknown warm ischemic time with minimal opportunity for organ assessment before circulatory arrest.46 Donors from these categories have been used for noncardiac organ procurement in France, Italy, and Spain.10 After family consent for organ donation and positive completion of the initial assessment for suitability, therapy is withdrawn (Figure 1).47

Figure 1.:
Comparison of donation pathways for DBD and category III DCD. The WHO organ donation pathway definitions are presented in italics.50 The duration of withdrawal of care and hands-off time for certification of legal death is variable in the DCD pathway in different jurisdictions.47 Cold ischemia is the most common preservation technique, the dotted line indicates the alternative pathways for allograft assessment and preservation: NRP53 and EVHP. Consent: consent for donation when applicable. Hands-off time: no clinical interaction with donor. DBD indicates donation after brain death; DCD, donation after circulatory death; EVHP, ex vivo heart perfusion; NRP, normothermic regional perfusion; WHO, World Health Organization.

In contrast to donation after brain death (DBD), DCD organs are not subjected to the physiological derangement associated with brain death and intracranial hypertension. Sparing the allografts from central neurologically mediated catecholamine release may explain the improved outcomes observed in lung transplantation from DCD donors, with 5-year survival rates of 90% compared to 61% in DBD donors.10

The main burden in DCD remains the ischemic allograft damage during the warm ischemic time (from when the systolic blood pressure drops below 50 mm Hg after withdrawal of care to reperfusion or cardioplegia).5,10,46 Based on animal models and previous clinical reports, DCD hearts are currently excluded from potential transplantation if the warm ischemic time exceeds 30 minutes.14,17,51

The warm ischemic time is terminated when cold hyperkalemic cardioplegia is injected into the aortic root, supplemented with pharmacological agents aimed at minimizing ischemic reperfusion injury.46 These agents include erythropoietin, antioxidants, insulin, sodium–hydrogen exchange inhibitors, adenosine, and glyceryl trinitrate, all of which contribute to improved myocardial recovery in cases of <30 minutes of warm ischemic time.52 Limiting factors to the widespread use of DCD allografts are ethical and legal concerns related to the definition of circulatory death. While brain death is widely accepted and defined worldwide, the assumption of brain death after a period of minimal (systolic arterial blood pressure <50 mm Hg) or no cerebral perfusion is certainly more controversial. For these reasons, regulations may vary significantly among countries. After withdrawal of life-sustaining therapies, the mandatory time period to declare the patient deceased, from when the systolic arterial blood pressure falls below 50 mm Hg, varies from 2 to 5 minutes of no interaction (stand off) in Australia, Canada, and the United Kingdom to 20 minutes of printed isoelectric electrocardiogram in Italy.46 Injection of systemic heparin is allowed before withdrawal of life support in some countries for better allograft preservation.

The first heart transplantation described >50 years ago was technically a DCD. The donor heart was procured in the neighboring operating theater while the recipient’s heart was excised. Warm ischemic time and travel time were minimal, which might have explained the lack of graft dysfunction despite the fact that neither early cardioplegia nor reperfusion were used. Approximately 70 DCD hearts have been transplanted in the United Kingdom and Australia to date.16,17


Once circulatory death has been declared and sternotomy is completed, normothermic regional perfusion may be used to minimize warm ischemic time and allow graft resuscitation for in vivo assessment. It implies the use of cardiopulmonary bypass via aortic root and right atrial cannulation after direct intracardiac injection of 30,000 international units of heparin while the cerebral circulation is excluded by cross-clamping of the head vessels to exclude perfusion of the brain and recirculation of catecholamines.53 The extracorporeal circuit maintains normothermic regional perfusion at a flow rate of 5 L/min with a mean arterial pressure of 50 mm Hg at 35°C. Infusions of dopamine and vasopressin are commenced, while troponin and lactate levels are used as indicators of organ preservation.53 After a period of reperfusion, mechanical support is weaned and functional assessment of the allograft is performed with transesophageal echocardiography and pulmonary artery catheterization.46,53

The accepted criteria for allograft suitability for transplantation include the following:53

  • I. Cardiac index ≥2.5 L/min/m2
  • II. Central venous pressure ≤12 mm Hg
  • III. Pulmonary capillary wedge pressure ≤12 mm Hg
  • IV. Left ventricular ejection fraction ≥50% on transesophageal echocardiography

These cutoff values are based on earlier studies with biventricular pressure–volume loop analysis performed in vivo with left ventricle (LV) loading before transplantation into low-risk recipients without evidence of pulmonary arterial hypertension.53

Reinstitution of circulation with exclusion of cerebral flow in a patient after declaration of circulatory death remains a contentious ethical issue. In the United Kingdom, it requires a specific informed consent endorsed by the National Health Service Blood and Transplant Service.54–56


Reduction in Cold Ischemia Time

EVHP has the potential for reducing adverse recipient outcomes by limiting the duration of cold ischemia.57 In animal models of transplanted DCD allografts, EVHP demonstrated functional recovery when compared to traditional cold storage.13 Similar findings were reported in humans when DBD allografts were preserved on EVHP. Recipients of perfused hearts showed reduced rates of PGD, acute rejection, and mortality at 30 days, 1 year, and 2 years, as well as lower requirements for postoperative extracorporeal circulatory support and massive transfusion when compared to traditional cold storage.58,59

Extension of Transportation Distance

EVHP may facilitate transportation across distances that would otherwise preclude transplantation due to unacceptably long duration of cold ischemia. EVHP for 611 minutes has been reported.60 Despite the initial need for support with extracorporeal membrane oxygenation, the recipient was eventually discharged with normal biventricular function and was reported to be rejection free at 1 year after transplantation.61

Optimization of Surgical Planning

The prolongation of the storage period may also potentially allow optimal surgical timing for implantation. In high-risk recipients requiring redo sternotomy or left ventricular assist device explant, EVHP could limit cold ischemia and allow extra time for dissection,62,63 while allowing more time for optimal patient matching.

Recovery and Preservation of DCD Hearts

The first report of successful transplantation of DCD hearts included EVHP preservation (>240 minutes) in 3 adults.17 In all cases, the initial right ventricular dysfunction resolved after 2 hours of EVHP. Central venoarterial extracorporeal membrane oxygenation was “prophylactically” used in 1 case. All 3 patients were alive at 1 year.

A series of 12 of Maastricht III DCD allografts reported successful preservation on EVHP for a mean of 302 minutes. Five patients required mechanical circulatory support postimplant, although normal biventricular function was documented at 30 days in all patients along with zero early mortality.64

Post-DCD, EVHP transportation after normothermic regional perfusion was no different than post-DBD, standard static cold storage with respect to the need for postoperative mechanical support, morbidity, or mortality up to 18 months postoperatively.65

Organ Care System

The Organ Care System developed by TransMedics (Andover, MA) is the only EVHP device that has been tested in clinical trials for human heart transplantation (Figure 2). It consists of a perfusion unit with an oxygenator, mounted on a transportation module. The perfusion unit is primed with 1.5 L of leukocyte-depleted heparinized donor blood and 500 mL of a proprietary TransMedics buffered electrolyte priming solution, supplemented with insulin, antibiotics, methylprednisolone, and multivitamins.17,66 The allograft, primarily arrested with standard cardioplegia, is placed on EVHP after cannulation of the great vessels, ligation of venae cavae, and left atrium. Oxygenated blood is delivered to the aortic root by a diaphragmatic pulsatile pump, which is synchronized with the electrocardiogram to allow peak coronary perfusion during diastole. Pump flow is maintained at 900–1200 mL/min to achieve coronary perfusion of 750–900 mL/min, measured as the returning flow from the pulmonary artery cannula.16,17,67 A plate heater maintains the perfusate at 34°C.66 Low-dose adenosine and epinephrine infusions are titrated to maintain a heart rate between 65 and 100 beats/min and an aortic root pressure between 65 to 90 mm Hg.17,66 Integrated pads allow defibrillation and pacing when required. As a measure of optimal metabolic function, a venous lactate of <5 mmol/L demonstrated appropriate myocardial lactate extraction.17

Figure 2.:
The Organ Care System (TransMedics, Andover, MA).69 Ao indicates aorta; AOF, aortic flow; ECG Defib, electrocardiogram defibrillator pads; Infusions, drug infusion ports; LA, left atrium; LV, left ventricle; Oxy, oxygenator; Pa, pulmonary artery; Ports, aortic, left ventricular, and pulmonary artery sampling ports; Pump, pulsatile pump; RA, right atrium; RV, right ventricle.

The Prospective multi-center, randomized, trial Investi gation of TransMedics Inc’s Organ Care System for cardiac use II Trial reported on 130 DBD allografts in which EVHP was noninferior despite a significantly longer time between harvesting and transplantation to traditional cold storage.68 Of note, 5 hearts were not transplanted due to rising lactate levels while on the ex vivo circuit. Outcomes at 2 years confirmed no significant differences in cardiac-related adverse events, allograft vasculopathy, and rejection.69 In view of these results, EVHP has been successfully used in 16 centers across 7 countries for >200 heart transplants.18

EVHP Evaluation and Allograft Optimization

Metabolic Assessment.

In the clinical setting, assessment of the allograft during EVHP currently relies on sampling lactate levels from the aortic root and pulmonary artery cannulas. The lactate level in the pulmonary artery perfusate corresponds to that in the coronary veins; values of >5 mmol/L were identified to predict graft dysfunction at 30 days.70 Other biomarkers of myocardial damage, such as troponin and creatine kinase, are of limited utility in predicting viability given their elevation due to the ischemic insult of warm ischemia and organ procurement.24,49,71,72

In animal DCD models, viable allografts at the time of harvesting presented a significant decrease in lactate extraction on EVHP.73

Similarly, human allografts viable for donation before explant demonstrated a poor metabolic profile on EVHP and were eventually deemed nonviable for transplantation.17

Functional Hemodynamic Assessment.

Functional assessment has been performed experimentally using transduction catheters to obtain pressure–volume loops-derived ventricular elastance74 during ventricular loading. The correlation of these measurements with outcomes after transplantation is being currently studied. In a porcine DCD model, catheter-derived pressure–volume loop parameters correlated with cardiac output indexed to myocardial mass. The hemodynamic parameters providing the best concurrence with myocardial performance were left ventricular ejection fraction, stroke work, and negative change in pressure/time.75 The lack of in vivo posttransplant assessment, however, does not allow correlation of these data with outcomes.

LV pressure–volume relationships obtained with a fluid-filled balloon have been used clinically to compare human DCD hearts with refused DBD allografts on EVHP.76 Four of 5 DCD hearts were successfully resuscitated on EVHP, and LV contractility was comparable with 5 DBD controls with a nonsignificant deterioration in DCD heart function after 2 hours. None of these hearts were transplanted.

A modified EVHP system allowing ventricular loading and pressure–volume loops evaluation has been proven feasible in the clinical evaluation of DCD allografts after normothermic regional perfusion. End-systolic elastance and the end-diastolic pressure–volume relationship were assessed in vivo and during EVHP.53 The aim of this study was to prove effectiveness of normothermic regional perfusion for DCD allografts, thus the correlation of invasive hemodynamic parameters on transplant outcome remains unclear.

Functional Echocardiographic Assessment.

Echocardiogra phy is a noninvasive method for functional biventricular assessment and has been used successfully in the experimental setting during EVHP.75 Epicardial echocardiography has been used to assess left ventricular fractional area change in animal models.77 In these studies, however, conductance catheter pressure measurements were not correlated with echocardiographic findings. Echocardiography has been used during EVHP to evaluate ejection fraction and ventricular wall thickness in porcine hearts using various perfusates at different temperatures and demonstrated preserved contractile function during warm perfusion. Short- and long-axis views of the LV were obtained reliably, allowing calculation of fractional area change, ejection fraction, and stroke volume on EVHP during ventricular loading.72

While ex vivo angiography has been used to evaluate donor hearts,78,79 no such clinical application of echocardiography during EVHP has been reported to date.

EVHP Limitations

The currently available EVHP technique has significant limitations.

Myocardial edema has been identified as an issue associated with prolonged EVHP, although it is uncertain whether the inevitable weight gain of the donor organ during this period translates to adverse outcomes in the recipient.71 Attempts to minimize cellular edema involve various perfusates, as well as synchronized pulsatile aortic flow to allow peak diastolic coronary perfusion while limiting excessive aortic root pressures.66,80 Further research into finding the optimal perfusion solution is ongoing.15,67 The restoration of physiological oncotic pressures may lead to a gradual reduction of myocyte edema and improvement in graft function.71,81

The evaluation of the heart ex vivo is currently limited to visual inspection and surrogate biomarkers only. Such assessment becomes essential if EVHP is to emerge as an opportunity to resuscitate extended criteria donor hearts. There is ongoing research currently underway with the international International Trial to Evaluate the Safety and Effectiveness of The Portable Organ Care System (OCS™) Heart For Preserving and Assessing Expanded Criteria Donor Hearts for Transplantation Heart Pivotal Trial (NCT02323321) looking at extended criteria allografts optimized on EVHP before transplantation.

At this stage, there do not appear to be reports of functional assessment of right ventricular performance on EVHP. This would be of great interest given the implication and frequency of right ventricular failure after heart transplant.

In addition to the current our knowledge gaps, the high EVHP costs (25,300 USD per allograft) significantly affect its adoption.

Future Directions

A major benefit of the EVHP procurement method is the ability to optimize and resuscitate the organ pharmacologically and monitor progress over time. Novel attempts at determining suitability for transplantation, like assessing myocardial contractile reserve by giving inotropes on the rig, could become of interest.

Pharmacological perfusate enhancements, such as erythropoietin, glyceryl trinitrate, zoniporide, and antioxidants for ischemic postconditioning and protection against PGD, show promising results in animal models.14,71 Standardized pharmacological treatment protocols are required for intensive ex vivo organ resuscitation. Thus far, these are in the early phase of evaluating appropriate drug titration. Further research continues into ideal EVHP pump pressures, appropriate hematocrit, and perfusion solutions to optimize myocytes’ metabolic milieu and limit cellular edema.71,80,82

As with any expansion of any new technology, acquisition of skills and familiarization with the technique will take some time before EVHP will be incorporated into routine transplantation practice. A substantial investment in logistics, personnel, and available financial resources is required to make EVHP available for routine organ resuscitation, assessment, and transplantation.8


The use of extended criteria donors, DCD hearts, and the introduction of ex vivo organ perfusion have already started to change the face of cardiac transplantation by expanding the donor pool. The potential for EVHP to enable organ assessment and optimization before implantation, as well as to prolong preservation times, has the potential to change our perception of the unfavorable donor and geographical distances as barriers to transplantation. As further research in this field is needed, data on long-term outcomes of recipients of extended donor and DCD allografts will continue to emerge and likely clarify the role of these new techniques as an integral part of allograft preservation and evaluation.


Name: Jodie Beuth, MBBS.

Contribution: This author helped perform all studies, collect and analyze all data, participate in creating the outline, and write the first draft of the manuscript and subsequent revised versions.

Name: Florian Falter, MD, PhD.

Contribution: This author helped review the final manuscript and provide original photographs.

Name: Roberto Vanin Pinto Ribeiro, MD.

Contribution: This author helped review the final manuscript.

Name: Mitesh Badiwala, MD, PhD.

Contribution: This author helped review the final manuscript.

Name: Massimiliano Meineri, MD, FASE.

Contribution: This author helped in conceiving this study and the experimental setup, supervise experimental measurements and data collection, create the outline, review the data quality, and analyze and edit the original manuscript and subsequent revised versions.

This manuscript was handled by: Nikoloas J. Skubas, MD, DSc, FACC, FASE.


1. Bassi N, Jeevanandam V. Choosing the right heart: proper donor selection in cardiac transplantation. Curr Opin Cardiol. 2017;32:86–291.
2. Kransdorf EP, Stehlik J. Donor evaluation in heart transplantation: the end of the beginning. J Heart Lung Transplant. 2014;33:1105–1113.
3. Luckraz H, Sharples LD, Charman SC, et al. Does heart transplantation confer survival benefit in all risk groups? J Heart Lung Transplant. 2005;24:1231–1234.
4. Kobashigawa J, Zuckermann A, Macdonald P, et al.; Consensus Conference ParticipantsReport from a consensus conference on primary graft dysfunction after cardiac transplantation. J Heart Lung Transplant. 2014;33:327–340.
5. Detry O, Le Dinh H, Noterdaeme T, et al. Categories of donation after cardiocirculatory death. Transplant Proc. 2012;44:1189–1195.
6. Stehlik J, Edwards LB, Kucheryavaya AY, et al.; International Society of Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: 29th official adult heart transplant report–2012. J Heart Lung Transplant. 2012;31:1052–1064.
7. Buckberg GD, Olinger GN, Mulder DG, Maloney JV Jr.. Depressed postoperative cardiac performance. Prevention by adequate myocardial protection during cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1975;70:974–994.
8. Bruns H, Schemmer P. Machine perfusion in solid organ transplantation: where is the benefit? Langenbecks Arch Surg. 2014;399:421–427.
9. Vogel T, Brockmann JG, Coussios C, Friend PJ. The role of normothermic extracorporeal perfusion in minimizing ischemia reperfusion injury. Transplant Rev (Orlando). 2012;26:156–162.
10. Citerio G, Cypel M, Dobb GJ, et al. Organ donation in adults: a critical care perspective. Intensive Care Med. 2016;42:305–315.
11. Cypel M, Yeung JC, Machuca T, et al. Experience with the first 50 ex vivo lung perfusions in clinical transplantation. J Thorac Cardiovasc Surg. 2012;144:1200–1206.
12. Tikkanen JM, Cypel M, Machuca TN, et al. Functional outcomes and quality of life after normothermic ex vivo lung perfusion lung transplantation. J Heart Lung Transplant. 2015;34:547–556.
13. Iyer A, Gao L, Doyle A, et al. Normothermic ex vivo perfusion provides superior organ preservation and enables viability assessment of hearts from DCD donors. Am J Transplant. 2015;15:371–380.
14. Iyer A, Gao L, Doyle A, et al. Increasing the tolerance of DCD hearts to warm ischemia by pharmacological postconditioning. Am J Transplant. 2014;14:1744–1752.
15. Minasian SM, Galagudza MM, Dmitriev YV, Karpov AA, Vlasov TD. Preservation of the donor heart: from basic science to clinical studies. Interact Cardiovasc Thorac Surg. 2015;20:510–519.
16. García Sáez D, Zych B, Sabashnikov A, et al. Evaluation of the organ care system in heart transplantation with an adverse donor/recipient profile. Ann Thorac Surg. 2014;98:2099–2105.
17. Dhital KK, Iyer A, Connellan M, et al. Adult heart transplantation with distant procurement and ex-vivo preservation of donor hearts after circulatory death: a case series. Lancet. 2015;385:2585–2591.
18. Fukushima N. Current status and future aspects of ex vivo allograft perfusion for heart transplantation. J Heart Lung Transplant. 2017;36:247–249.
19. Kilic A, Emani S, Sai-Sudhakar CB, Higgins RS, Whitson BA. Donor selection in heart transplantation. J Thorac Dis. 2014;6:1097–1104.
20. Kobashigawa J, Khush K, Colvin M, et al. Report from the American Society of Transplantation Conference on Donor Heart Selection in Adult Cardiac Transplantation in the United States. Am J Transplant. 2017;17:2559–2566.
21. Smith JW, O’Brien KD, Dardas T, et al. Systematic donor selection review process improves cardiac transplant volumes and outcomes. J Thorac Cardiovasc Surg. 2016;151:238–243.
22. Jeevanandam V, Furukawa S, Prendergast TW, Todd BA, Eisen HJ, McClurken JB. Standard criteria for an acceptable donor heart are restricting heart transplantation. Ann Thorac Surg. 1996;62:1268–1275.
23. Lund LH, Edwards LB, Dipchand AI, et al.; International Society for Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: thirty-third adult heart transplantation report-2016; focus theme: primary diagnostic indications for transplant. J Heart Lung Transplant. 2016;35:1158–1169.
24. Zaroff JG, Rosengard BR, Armstrong WF, et al. Consensus conference report: maximizing use of organs recovered from the cadaver donor: cardiac recommendations, March 28–29, 2001, Crystal City, VA. Circulation. 2002;106:836–841.
25. Marelli D, Laks H, Bresson S, et al. Results after transplantation using donor hearts with preexisting coronary artery disease. J Thorac Cardiovasc Surg. 2003;126:821–825.
26. Carrier M, Lizé JF; Québec-Transplant Programs. Impact of expanded-criteria donors on patient survival after heart, lung, liver and combined organ transplantation. Transplant Proc. 2012;44:2231–2234.
27. Lund LH, Edwards LB, Kucheryavaya AY, et al.; International Society for Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: thirtieth official adult heart transplant report–2013; focus theme: age. J Heart Lung Transplant. 2013;32:951–964.
28. Samsky MD, Patel CB, Owen A, et al. Ten-year experience with extended criteria cardiac transplantation. Circ Heart Fail. 2013;6:1230–1238.
29. Fiorelli AI, Branco JN, Dinkhuysen JJ, et al. Risk factor analysis of late survival after heart transplantation according to donor profile: a multi-institutional retrospective study of 512 transplants. Transplant Proc. 2012;44:2469–2472.
30. Marelli AJ, Ionescu-Ittu R, Mackie AS, Guo L, Dendukuri N, Kaouache M. Lifetime prevalence of congenital heart disease in the general population from 2000 to 2010. Circulation. 2014;130:749–756.
31. John R. Donor management and selection for heart transplantation. Semin Thorac Cardiovasc Surg. 2004;16:364–369.
32. Grauhan O, Siniawski H, Dandel M, et al. Coronary atherosclerosis of the donor heart–impact on early graft failure. Eur J Cardiothorac Surg. 2007;32:634–638.
33. Tsao CI, Chen RJ, Chou NK, et al. The influence of donor characteristics on survival after heart transplantation. Transplant Proc. 2008;40:2636–2637.
34. Stehlik J, Feldman DS, Brown RN, et al.; Cardiac Transplant Research Database Group. Interactions among donor characteristics influence post-transplant survival: a multi-institutional analysis. J Heart Lung Transplant. 2010;29:291–298.
35. Topkara VK, Cheema FH, Kesavaramanujam S, et al. Effect of donor age on long-term survival following cardiac transplantation. J Card Surg. 2006;21:125–129.
36. Venkateswaran RV, Dronavalli V, Lambert PA, et al. The proinflammatory environment in potential heart and lung donors: prevalence and impact of donor management and hormonal therapy. Transplantation. 2009;88:582–588.
37. Dronavalli VB, Banner NR, Bonser RS. Assessment of the potential heart donor: a role for biomarkers? J Am Coll Cardiol. 2010;56:352–361.
38. Madan S, Saeed O, Shin J, et al. Donor troponin and survival after cardiac transplantation: an analysis of the United Network of Organ Sharing Registry. Circ Heart Fail. 2016;9:e002909.
39. Russo MJ, Iribarne A, Hong KN, et al. Factors associated with primary graft failure after heart transplantation. Transplantation. 2010;90:444–450.
40. Wittwer T, Wahlers T. Marginal donor grafts in heart transplantation: lessons learned from 25 years of experience. Transpl Int. 2008;21:113–125.
41. Costanzo MR, Dipchand A, Starling R, et al.; International Society of Heart and Lung Transplantation Guidelines. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010;29:914–956.
42. Hertz MI, Aurora P, Christie JD, et al. Scientific Registry of the International Society for Heart and Lung Transplantation: introduction to the 2009 annual reportsJ Heart Lung Transplant. 2009;28:989–992.
43. Goldsmith KA, Demiris N, Gooi JH, et al. Life-years gained by reducing donor heart ischemic times. Transplantation. 2009;87:243–248.
44. Lund LH, Edwards LB, Kucheryavaya AY, et al. The registry of the International Society for Heart and Lung Transplantation: thirty-second official adult heart transplantation report—2015; focus theme: early graft failure. J Heart Lung Transplant. 2015;34:1244–1254.
45. Banner NR, Thomas HL, Curnow E, Hussey JC, Rogers CA, Bonser RS; Steering Group of the United Kingdom Cardiothoracic Transplant Audit. The importance of cold and warm cardiac ischemia for survival after heart transplantation. Transplantation. 2008;86:542–547.
46. Dhital KK, Chew HC, Macdonald PS. Donation after circulatory death heart transplantation. Curr Opin Organ Transplant. 2017;22:189–197.
47. Abt PL, Fisher CA, Singhal AK. Donation after cardiac death in the US: history and use. J Am Coll Surg. 2006;203:208–225.
48. Kootstra G, Daemen JH, Oomen AP. Categories of non-heart-beating donors. Transplant Proc. 1995;27:2893–2894.
49. Kotloff RM, Blosser S, Fulda GJ, et al.; Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Donor Management Task Force. Management of the potential organ donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement. Crit Care Med. 2015;43:1291–1325.
50. Evrard P; Belgian Working Group on DCD National Protocol. Belgian modified classification of Maastricht for donors after circulatory death. Transplant Proc. 2014;46:3138–3142.
51. Colah S, Freed DH, Mundt P, et al. Ex vivo perfusion of the swine heart as a method for pre-transplant assessment. Perfusion. 2012;27:408–413.
52. Sanada S, Komuro I, Kitakaze M. Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning, and translational aspects of protective measures. Am J Physiol Heart Circ Physiol. 2011;301:H1723–H1741.
53. Messer SJ, Axell RG, Colah S, et al. Functional assessment and transplantation of the donor heart after circulatory death. J Heart Lung Transplant. 2016;35:1443–1452.
54. Dalle Ave AL, Shaw D, Bernat JL. An analysis of heart donation after circulatory determination of death. J Med Ethics. 2016;42:312–317.
55. Institute of Medicine. Non-Heart-Beating Organ Transplantation: Practice and Protocols. 2000.Washington, DC: The National Academies Press.
56. Rowinski W, Paczek L. Transplantation ethics: are we approaching the crossroads? Transplant Proc. 2012;44:2171–2172.
57. Freed DH, White CW. Donor heart preservation: straight up, or on the rocks? Lancet. 2015;385:2552–2554.
58. Koerner MM, Ghodsizad A, Schulz U, El Banayosy A, Koerfer R, Tenderich G. Normothermic ex vivo allograft blood perfusion in clinical heart transplantation. Heart Surg Forum. 2014;17:E141–E145.
59. Garcia Saez D, Zych B, Mohite P, et al. LVAD bridging to heart transplantation with ex vivo allograft preservation shows significantly improved: outcomes: a new standard of care? J Heart Lung Transplantat. 2015;34:S95.
60. Stamp NL, Shah A, Vincent V, et al. Successful heart transplant after ten hours out-of-body time using the TransMedics Organ Care System. Heart Lung Circ. 2015;24:611–613.
61. Stamp NL, Larbalestier RI. Response to ‘ex-vivo donor heart perfusion: testing the limits of cardiac resilience.’ Heart Lung Circ. 2015;24:1239–1240.
62. Leprince P, Popov AF, Simon AR, Benk C, Siepe M. Ex vivo perfusion of the heart with the use of the Organ Care System. Eur J Cardiothorac Surg. 2016;49:1318–1320.
63. Popov AF, García Sáez D, Sabashnikov A, et al. Utilization of the organ care system - a game-changer in combating donor organ shortage. Med Sci Monit Basic Res. 2015;21:29–32.
64. Dhital KK, Connellan M, Chew HC, et al. Rapid retrieval and ex situ portable machine perfusion allows successful cardiac transplantation with donor hearts from controlled donation after circulatory death. J Heart Lung Transplant. 2017;36:S16.
65. Messer S, Page A, Axell R, et al. Excellent early outcomes following heart transplantation from circulatory dead donors. J Heart Lung Transplant. 2017;36:S15–S16.
66. Messer S, Ardehali A, Tsui S. Normothermic donor heart perfusion: current clinical experience and the future. Transpl Int. 2015;28:634–642.
67. Macdonald PS, Chew HC, Connellan M, Dhital K. Extracorporeal heart perfusion before heart transplantation: the heart in a box. Curr Opin Organ Transplant. 2016;21:336–342.
68. Ardehali A, Esmailian F, Deng M, et al.; PROCEED II TrialInvestigators. Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial. Lancet. 2015;385:2577–2584.
69. Chan JL, Kobashigawa JA, Reich HJ, et al. Intermediate outcomes with ex-vivo allograft perfusion for heart transplantation. J Heart Lung Transplant. 2017;36:258–263.
70. Hamed A, Tsui S, Huber J, Lin R, Poggio EC, Ardehali A. 19: serum lactate is a highly sensitive and specific predictor of post cardiac transplant outcomes using the Organ Care System. J Heart Lung Transplant. 2009;28:S71.
71. Collins MJ, Moainie SL, Griffith BP, Poston RS. Preserving and evaluating hearts with ex vivo machine perfusion: an avenue to improve early graft performance and expand the donor pool. Eur J Cardiothorac Surg. 2008;34:318–325.
72. Lowalekar SK, Cao H, Lu XG, Treanor PR, Thatte HS. Subnormothermic preservation in Somah: a novel approach for enhanced functional resuscitation of donor hearts for transplant. Am J Transplant. 2014;14:2253–2262.
73. García Sáez D, Elbetanony A, Lezberg P, et al. Ex vivo heart perfusion after cardiocirculatory death: a porcine model. J Surg Res. 2015;195:311–314.
74. Rosenbaum DH, Peltz M, DiMaio JM, et al. Perfusion preservation versus static preservation for cardiac transplantation: effects on myocardial function and metabolism. J Heart Lung Transplant. 2008;27:93–99.
75. White CW, Ambrose E, Müller A, et al. Assessment of donor heart viability during ex vivo heart perfusion. Can J Physiol Pharmacol. 2015;93:893–901.
76. Osaki S, Locher MR, Lushaj EB, Akhter SA, Kohmoto T. Functional evaluation of human donation after cardiac death donor hearts using a continuous isolated myocardial perfusion technique: potential for expansion of the cardiac donor population. J Thorac Cardiovasc Surg. 2014;148:1123–1130.
77. Repse S, Pepe S, Anderson J, McLean C, Rosenfeldt FL. Cardiac reanimation for donor heart transplantation after cardiocirculatory death. J Heart Lung Transplant. 2010;29:747–755.
78. Ghodsizad A, Bordel V, Ungerer M, Karck M, Bekeredjian R, Ruhparwar A. Ex vivo coronary angiography of a donor heart in the organ care system. Heart Surg Forum. 2012;15:E161–E163.
79. Anthony C, Michel J, Christofi M, et al. Ex vivo coronary angiographic evaluation of a beating donor heart. Circulation. 2014;130:e341–e343.
80. Smulowitz PB, Serna DL, Beckham GE, Milliken JC. Ex vivo cardiac allograft preservation by continuous perfusion techniques. ASAIO J. 2000;46:389–396.
81. Dhital K, Simon A, Macdonald P. Ex-vivo donor heart perfusion: testing the limits of cardiac resilience. Heart Lung Circ. 2015;24:1191–1192.
82. White CW, Ali A, Hasanally D, et al. A cardioprotective preservation strategy employing ex vivo heart perfusion facilitates successful transplant of donor hearts after cardiocirculatory death. J Heart Lung Transplant. 2013;32:734–743.
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