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How do you mend a donor heart?
Author’s Accepted Manuscript How do you mend a donor heart? Peter Macdonald
http://www.jhltonline.org
PII: DOI: Reference:
S1053-2498(17)31708-4S1053-2498(17)31348-7 http://dx.doi.org/10.1016/j.healun.2017.03.011 HEALUN6484
To appear in: Journal of Heart and Lung Transplantation Cite this article as: Peter Macdonald, How do you mend a donor heart?, Journal of Heart and Lung Transplantation, http://dx.doi.org/10.1016/j.healun.2017.03.011 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
How do you mend a donor heart? Peter Macdonald MD PHD FRACP Medical Director, Heart Transplant Unit, St Vincent’s Hospital, Darlinghurst, NSW, Australia 2010 Director, Transplantation Research Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst NSW 2010 Conjoint Professor of Medicine, University of New South Wales, Sydney, NSW
Imagine the following scenario. A previously fit 23 year old male with no known medical history has fallen from a 2nd floor balcony and sustained critical head injuries. He is found unconscious on the pavement and taken by ambulance to his local hospital. After 24 hours in the ICU he experiences a hypertensive crisis then becomes increasingly haemodynamically unstable. He has received an escalating concentration of norepinephrine but with little improvement in his haemodynamics. Brain death testing confirms brain death and his next of kin consent to multi-organ donation. An echocardiogram is performed 3 hours after brain death testing and reported as showing severe generalized global left ventricular dysfunction with an estimated ejection fraction of 25%. The local donor coordinator contacts you as the heart transplant physician/surgeon and asks whether you will accept this heart for transplantation. What would you do? In the above scenario there is a very strong suspicion that the severe left ventricular dysfunction is an acute phenomenon resulting from brain death and that this will reverse over time. The problem is that we have no way of knowing whether this is the case. Even if we accept that the left ventricular dysfunction has been caused by brain death we do not know whether the heart will recover and if so how long this will take. Acute severe left ventricular dysfunction occurring in association with severe neurological injury is a well-recognized phenomenon and has been reported in more than 40% of patients who progress to brain death (1). A close comparison has been drawn between this phenomenon and the Takotsubo cardiomyopathy that occurs in individuals subjected to extreme emotional stress (2). Both entities are thought to be mediated by exposure of the heart to an abrupt extreme elevation of endogenous catecholamines resulting in microvascular coronary vasoconstriction, myocardial stunning and a characteristic histopathological lesion of contraction band necrosis. Both entities also typically respond poorly to administration of exogenous catecholamines (3-5), another clue that the severe myocardial dysfunction in our imaginary case has been caused by brain death and its sequelae. Another characteristic clinical feature of Takotsubo cardiomyopathy is the high rate of myocardial recovery over ensuing days for the large majority of patients (6). Does the same prognosis apply for the severely dysfunctional heart after brain death? We do know that aggressive donor management possibly with combined hormonal resuscitation increases the yield of all donor organs including the heart from brain
dead donors (7-9). Although there is limited published data on serial echocardiograms performed in the same donor, those that have been published indicate that hearts that were dysfunctional at the initial echocardiogram often demonstrate improved function after commencement of aggressive donor management (10). Improvement in donor heart function during donor management has been reported in both children and adults (11, 12). The average time between initial and follow-up echocardiograms in these two studies was approximately 20 hours. Interestingly, in the adult series, potential donors with left ventricular dysfunction on initial echocardiogram were significantly younger than donors with normal left ventricular function suggesting that the reversible cardiac dysfunction after brain death may be more common in younger donors. In both series hearts that recovered normal function on follow-up echocardiography were transplanted with good recipient outcomes whereas hearts that continued to display myocardial dysfunction were not used. While this is an encouraging outcome, the question remains as to whether hearts that remain dysfunctional after a period of donor management still have the potential to regain normal function after transplantation. In this issue of the Journal, Chen and colleagues have published the results of a UNOS Registry analysis in which they compared the outcomes of recipients of donor hearts that were recorded in the UNOS database as having reduced (LVEF < 40%), borderline (LVEF 40-50%) or normal (LVEF >50%) heart function (13). The average age of the reduced LVEF donors was 23 years, significantly younger than donors with borderline or normal LVEF transplanted in the same era. As mentioned previously, this could be explained by the possibility that transient myocardial dysfunction after brain death is more common in younger donors. Alternatively, it may reflect a selection bias on the part of the transplanting surgeon who is more confident that a reduced LVEF heart from a young donor will recover whereas the same heart from an older donor may not. Not surprisingly, there were very few patients in the reduced or borderline groups compared with the normal group. Nonetheless, the overall clinical outcomes and graft function at one year posttransplant were similar for all 3 groups. These data suggest that at least a proportion of low LVEF donor hearts have the capacity to recover normal function posttransplant. Again these findings are encouraging, however a number of limitations which are inherent to the UNOS database deserve comment. It is unknown how many of the reduced and borderline LVEF hearts underwent repeated echocardiographic evaluation in the donor and if so whether the echocardiogram recorded in the database was the first one recorded after brain death or the one closest to the time of retrieval. It is possible that a number of hearts classified as reduced or borderline LVEF on the initial echocardiogram may have regained normal function prior to retrieval. A second limitation is the lack of information in the database about primary graft dysfunction and the need for early mechanical support post-transplant. It would be valuable to know whether recipients of reduced LVEF hearts required more mechanical circulatory support than recipients of normal LVEF hearts. In a recently reported series from our centre, Rao and colleagues described the outcome of 21 recipients of reduced LVEF donor hearts with an average LVEF of 36% on the last echocardiogram prior to retrieval (14). More than 50% of the recipients of low EF donor hearts reported in the series came out of operating room
on ECMO support however their long-term outcome in terms of survival and graft function was similar to that of recipients of normal LVEF donor hearts (14). It seems likely based on the UNOS analysis undertaken by Chen et al and publications by others that many donor hearts with impaired cardiac function at initial assessment have the capacity to recover normal heart function either during subsequent donor management or after transplantation. If the donor heart recovers normal function during donor management then the decision to transplant this heart is relatively straightforward. The decision making around hearts that remain dysfunctional despite aggressive donor management is more challenging. One possible solution is normothermic machine perfusion of the donor heart. This technology has been applied successfully to determine the viability of hearts retrieved from donation after circulatory death (DCD) donors (15) and also of extended criteria hearts retrieved from brain dead donors (16), however the application of this technology to these types of donors is still in its infancy. The retrieval of hearts from brain dead donors has been declining. Currently, hearts are retrieved and transplanted from only 20-30% of brain dead donors. There are a number of possible reasons for this. As organ donation rates have increased across multiple jurisdictions most of the increase has been in categories considered either high-risk or unsuitable for heart transplantation. One of the major reasons for nonutilisation of donor hearts is the presence of myocardial dysfunction after brain death. Another possible reason for the decline in utilization of donor hearts in the current era is that heart transplant waiting lists are increasingly populated by patients who have been stabilized on long-term mechanical support. There is an understandable reluctance on the part of heart transplant surgeons to utilize suboptimal donor hearts for this stable group of patients. A third potential reason is at a systems level in which the regulatory environment acts as a major disincentive to clinicians operating outside of strictly prescribed clinical guidelines. The major consequence of the declining utilization of hearts from brain dead donors is a widening gap between the availability of donor hearts and recipient need. This trend is unlikely to change unless we as clinicians are prepared to reconsider the use of marginal hearts – low LVEF hearts from young donors may be a good place to start.
Acknowledgements None to declare
References.
1. Dujardin KS, McCully RB, Wijdicks EF, Tazelaar HD, Seward JB, McGregor CG, et al. Myocardial dysfunction associated with brain death: clinical, echocardiographic, and pathologic features. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2001 Mar;20(3):350-7. PubMed PMID: 11257562. 2. Berman M, Ali A, Ashley E, Freed D, Clarke K, Tsui S, et al. Is stress cardiomyopathy the underlying cause of ventricular dysfunction associated with brain death? The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2010 Sep;29(9):957-65. PubMed PMID: 20627624. 3. Mrozek S, Srairi M, Marhar F, Delmas C, Gaussiat F, Abaziou T, et al. Successful treatment of inverted Takotsubo cardiomyopathy after severe traumatic brain injury with milrinone after dobutamine failure. Heart & lung : the journal of critical care. 2016 Sep-Oct;45(5):406-8. PubMed PMID: 27402629. 4. Brunetti ND, Santoro F, De Gennaro L, Correale M, Kentaro H, Gaglione A, et al. Therapy of stress (takotsubo) cardiomyopathy: present shortcomings and future perspectives. Future cardiology. 2016 Sep;12(5):563-72. PubMed PMID: 27538839. 5. Hing AJ, Hicks M, Garlick SR, Gao L, Kesteven SH, Faddy SC, et al. The effects of hormone resuscitation on cardiac function and hemodynamics in a porcine brain-dead organ donor model. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2007 Apr;7(4):809-17. PubMed PMID: 17331116. 6. Sharkey SW, Windenburg DC, Lesser JR, Maron MS, Hauser RG, Lesser JN, et al. Natural history and expansive clinical profile of stress (tako-tsubo) cardiomyopathy. Journal of the American College of Cardiology. 2010 Jan 26;55(4):333-41. PubMed PMID: 20117439. 7. Rosendale JD, Kauffman HM, McBride MA, Chabalewski FL, Zaroff JG, Garrity ER, et al. Hormonal resuscitation yields more transplanted hearts, with improved early function. Transplantation. 2003;75(8):1336-41. 8. Novitzky D, Cooper DK, Rosendale JD, Kauffman HM. Hormonal therapy of the brain-dead organ donor: experimental and clinical studies. Transplantation. 2006 Dec 15;82(11):1396-401. PubMed PMID: 17164704. 9. Wheeldon DR, Potter CD, Oduro A, Wallwork J, Large SR. Transforming the "unacceptable" donor: outcomes from the adoption of a standardized donor management technique. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 1995 JulAug;14(4):734-42. PubMed PMID: 7578183. 10. Zaroff JG, Babcock WD, Shiboski SC, Solinger LL, Rosengard BR. Temporal changes in left ventricular systolic function in heart donors: results of serial echocardiography. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2003 Apr;22(4):383-8. PubMed PMID: 12681416. 11. Borbely XI, Krishnamoorthy V, Modi S, Rowhani-Rahbar A, Gibbons E, Souter MJ, et al. Temporal Changes in Left Ventricular Systolic Function and Use of
Echocardiography in Adult Heart Donors. Neurocritical care. 2015 Aug;23(1):66-71. PubMed PMID: 25561433. 12. Krishnamoorthy V, Borbely X, Rowhani-Rahbar A, Souter MJ, Gibbons E, Vavilala MS. Cardiac dysfunction following brain death in children: prevalence, normalization, and transplantation. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2015 May;16(4):e107-12. PubMed PMID: 25828779. Pubmed Central PMCID: 4424099. 13. Chen CW, Sprys MH, Gaffey AC, Chung JJ, Margulies KB, Acker MA, et al. Low Ejection Fraction in Donor Hearts Is Not Directly Associated with Increased Recipient Mortality. Journal of Heart and Lung Transplantation. 2017;(in press). 14. Rao SD, Watson A, Lo P, Jabbour A, Hayward CS, Keogh AM, et al. Successful Orthotropic Heart Transplantation Using Donors With Left Ventricular Systolic Dysfunction: Evidence for Brain Death-Induced Takotsubo Cardiomyopathy. Journal of Heart and Lung Transplantation. 2015;34(4):S71-S2. 15. Dhital KK, Iyer A, Connellan M, Chew HC, Gao L, Doyle A, et al. Adult heart transplantation with distant procurement and ex-vivo preservation of donor hearts after circulatory death: a case series. Lancet. 2015 Jun 27;385(9987):2585-91. PubMed PMID: 25888085. 16. Garcia Saez D, Zych B, Sabashnikov A, Bowles CT, De Robertis F, Mohite PN, et al. Evaluation of the organ care system in heart transplantation with an adverse donor/recipient profile. The Annals of thoracic surgery. 2014 Dec;98(6):2099-105; discussion 105-6. PubMed PMID: 25443013.
http://www.jhltonline.org
PII: DOI: Reference:
S1053-2498(17)31708-4S1053-2498(17)31348-7 http://dx.doi.org/10.1016/j.healun.2017.03.011 HEALUN6484
To appear in: Journal of Heart and Lung Transplantation Cite this article as: Peter Macdonald, How do you mend a donor heart?, Journal of Heart and Lung Transplantation, http://dx.doi.org/10.1016/j.healun.2017.03.011 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
How do you mend a donor heart? Peter Macdonald MD PHD FRACP Medical Director, Heart Transplant Unit, St Vincent’s Hospital, Darlinghurst, NSW, Australia 2010 Director, Transplantation Research Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst NSW 2010 Conjoint Professor of Medicine, University of New South Wales, Sydney, NSW
Imagine the following scenario. A previously fit 23 year old male with no known medical history has fallen from a 2nd floor balcony and sustained critical head injuries. He is found unconscious on the pavement and taken by ambulance to his local hospital. After 24 hours in the ICU he experiences a hypertensive crisis then becomes increasingly haemodynamically unstable. He has received an escalating concentration of norepinephrine but with little improvement in his haemodynamics. Brain death testing confirms brain death and his next of kin consent to multi-organ donation. An echocardiogram is performed 3 hours after brain death testing and reported as showing severe generalized global left ventricular dysfunction with an estimated ejection fraction of 25%. The local donor coordinator contacts you as the heart transplant physician/surgeon and asks whether you will accept this heart for transplantation. What would you do? In the above scenario there is a very strong suspicion that the severe left ventricular dysfunction is an acute phenomenon resulting from brain death and that this will reverse over time. The problem is that we have no way of knowing whether this is the case. Even if we accept that the left ventricular dysfunction has been caused by brain death we do not know whether the heart will recover and if so how long this will take. Acute severe left ventricular dysfunction occurring in association with severe neurological injury is a well-recognized phenomenon and has been reported in more than 40% of patients who progress to brain death (1). A close comparison has been drawn between this phenomenon and the Takotsubo cardiomyopathy that occurs in individuals subjected to extreme emotional stress (2). Both entities are thought to be mediated by exposure of the heart to an abrupt extreme elevation of endogenous catecholamines resulting in microvascular coronary vasoconstriction, myocardial stunning and a characteristic histopathological lesion of contraction band necrosis. Both entities also typically respond poorly to administration of exogenous catecholamines (3-5), another clue that the severe myocardial dysfunction in our imaginary case has been caused by brain death and its sequelae. Another characteristic clinical feature of Takotsubo cardiomyopathy is the high rate of myocardial recovery over ensuing days for the large majority of patients (6). Does the same prognosis apply for the severely dysfunctional heart after brain death? We do know that aggressive donor management possibly with combined hormonal resuscitation increases the yield of all donor organs including the heart from brain
dead donors (7-9). Although there is limited published data on serial echocardiograms performed in the same donor, those that have been published indicate that hearts that were dysfunctional at the initial echocardiogram often demonstrate improved function after commencement of aggressive donor management (10). Improvement in donor heart function during donor management has been reported in both children and adults (11, 12). The average time between initial and follow-up echocardiograms in these two studies was approximately 20 hours. Interestingly, in the adult series, potential donors with left ventricular dysfunction on initial echocardiogram were significantly younger than donors with normal left ventricular function suggesting that the reversible cardiac dysfunction after brain death may be more common in younger donors. In both series hearts that recovered normal function on follow-up echocardiography were transplanted with good recipient outcomes whereas hearts that continued to display myocardial dysfunction were not used. While this is an encouraging outcome, the question remains as to whether hearts that remain dysfunctional after a period of donor management still have the potential to regain normal function after transplantation. In this issue of the Journal, Chen and colleagues have published the results of a UNOS Registry analysis in which they compared the outcomes of recipients of donor hearts that were recorded in the UNOS database as having reduced (LVEF < 40%), borderline (LVEF 40-50%) or normal (LVEF >50%) heart function (13). The average age of the reduced LVEF donors was 23 years, significantly younger than donors with borderline or normal LVEF transplanted in the same era. As mentioned previously, this could be explained by the possibility that transient myocardial dysfunction after brain death is more common in younger donors. Alternatively, it may reflect a selection bias on the part of the transplanting surgeon who is more confident that a reduced LVEF heart from a young donor will recover whereas the same heart from an older donor may not. Not surprisingly, there were very few patients in the reduced or borderline groups compared with the normal group. Nonetheless, the overall clinical outcomes and graft function at one year posttransplant were similar for all 3 groups. These data suggest that at least a proportion of low LVEF donor hearts have the capacity to recover normal function posttransplant. Again these findings are encouraging, however a number of limitations which are inherent to the UNOS database deserve comment. It is unknown how many of the reduced and borderline LVEF hearts underwent repeated echocardiographic evaluation in the donor and if so whether the echocardiogram recorded in the database was the first one recorded after brain death or the one closest to the time of retrieval. It is possible that a number of hearts classified as reduced or borderline LVEF on the initial echocardiogram may have regained normal function prior to retrieval. A second limitation is the lack of information in the database about primary graft dysfunction and the need for early mechanical support post-transplant. It would be valuable to know whether recipients of reduced LVEF hearts required more mechanical circulatory support than recipients of normal LVEF hearts. In a recently reported series from our centre, Rao and colleagues described the outcome of 21 recipients of reduced LVEF donor hearts with an average LVEF of 36% on the last echocardiogram prior to retrieval (14). More than 50% of the recipients of low EF donor hearts reported in the series came out of operating room
on ECMO support however their long-term outcome in terms of survival and graft function was similar to that of recipients of normal LVEF donor hearts (14). It seems likely based on the UNOS analysis undertaken by Chen et al and publications by others that many donor hearts with impaired cardiac function at initial assessment have the capacity to recover normal heart function either during subsequent donor management or after transplantation. If the donor heart recovers normal function during donor management then the decision to transplant this heart is relatively straightforward. The decision making around hearts that remain dysfunctional despite aggressive donor management is more challenging. One possible solution is normothermic machine perfusion of the donor heart. This technology has been applied successfully to determine the viability of hearts retrieved from donation after circulatory death (DCD) donors (15) and also of extended criteria hearts retrieved from brain dead donors (16), however the application of this technology to these types of donors is still in its infancy. The retrieval of hearts from brain dead donors has been declining. Currently, hearts are retrieved and transplanted from only 20-30% of brain dead donors. There are a number of possible reasons for this. As organ donation rates have increased across multiple jurisdictions most of the increase has been in categories considered either high-risk or unsuitable for heart transplantation. One of the major reasons for nonutilisation of donor hearts is the presence of myocardial dysfunction after brain death. Another possible reason for the decline in utilization of donor hearts in the current era is that heart transplant waiting lists are increasingly populated by patients who have been stabilized on long-term mechanical support. There is an understandable reluctance on the part of heart transplant surgeons to utilize suboptimal donor hearts for this stable group of patients. A third potential reason is at a systems level in which the regulatory environment acts as a major disincentive to clinicians operating outside of strictly prescribed clinical guidelines. The major consequence of the declining utilization of hearts from brain dead donors is a widening gap between the availability of donor hearts and recipient need. This trend is unlikely to change unless we as clinicians are prepared to reconsider the use of marginal hearts – low LVEF hearts from young donors may be a good place to start.
Acknowledgements None to declare
References.
1. Dujardin KS, McCully RB, Wijdicks EF, Tazelaar HD, Seward JB, McGregor CG, et al. Myocardial dysfunction associated with brain death: clinical, echocardiographic, and pathologic features. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2001 Mar;20(3):350-7. PubMed PMID: 11257562. 2. Berman M, Ali A, Ashley E, Freed D, Clarke K, Tsui S, et al. Is stress cardiomyopathy the underlying cause of ventricular dysfunction associated with brain death? The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2010 Sep;29(9):957-65. PubMed PMID: 20627624. 3. Mrozek S, Srairi M, Marhar F, Delmas C, Gaussiat F, Abaziou T, et al. Successful treatment of inverted Takotsubo cardiomyopathy after severe traumatic brain injury with milrinone after dobutamine failure. Heart & lung : the journal of critical care. 2016 Sep-Oct;45(5):406-8. PubMed PMID: 27402629. 4. Brunetti ND, Santoro F, De Gennaro L, Correale M, Kentaro H, Gaglione A, et al. Therapy of stress (takotsubo) cardiomyopathy: present shortcomings and future perspectives. Future cardiology. 2016 Sep;12(5):563-72. PubMed PMID: 27538839. 5. Hing AJ, Hicks M, Garlick SR, Gao L, Kesteven SH, Faddy SC, et al. The effects of hormone resuscitation on cardiac function and hemodynamics in a porcine brain-dead organ donor model. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2007 Apr;7(4):809-17. PubMed PMID: 17331116. 6. Sharkey SW, Windenburg DC, Lesser JR, Maron MS, Hauser RG, Lesser JN, et al. Natural history and expansive clinical profile of stress (tako-tsubo) cardiomyopathy. Journal of the American College of Cardiology. 2010 Jan 26;55(4):333-41. PubMed PMID: 20117439. 7. Rosendale JD, Kauffman HM, McBride MA, Chabalewski FL, Zaroff JG, Garrity ER, et al. Hormonal resuscitation yields more transplanted hearts, with improved early function. Transplantation. 2003;75(8):1336-41. 8. Novitzky D, Cooper DK, Rosendale JD, Kauffman HM. Hormonal therapy of the brain-dead organ donor: experimental and clinical studies. Transplantation. 2006 Dec 15;82(11):1396-401. PubMed PMID: 17164704. 9. Wheeldon DR, Potter CD, Oduro A, Wallwork J, Large SR. Transforming the "unacceptable" donor: outcomes from the adoption of a standardized donor management technique. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 1995 JulAug;14(4):734-42. PubMed PMID: 7578183. 10. Zaroff JG, Babcock WD, Shiboski SC, Solinger LL, Rosengard BR. Temporal changes in left ventricular systolic function in heart donors: results of serial echocardiography. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2003 Apr;22(4):383-8. PubMed PMID: 12681416. 11. Borbely XI, Krishnamoorthy V, Modi S, Rowhani-Rahbar A, Gibbons E, Souter MJ, et al. Temporal Changes in Left Ventricular Systolic Function and Use of
Echocardiography in Adult Heart Donors. Neurocritical care. 2015 Aug;23(1):66-71. PubMed PMID: 25561433. 12. Krishnamoorthy V, Borbely X, Rowhani-Rahbar A, Souter MJ, Gibbons E, Vavilala MS. Cardiac dysfunction following brain death in children: prevalence, normalization, and transplantation. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2015 May;16(4):e107-12. PubMed PMID: 25828779. Pubmed Central PMCID: 4424099. 13. Chen CW, Sprys MH, Gaffey AC, Chung JJ, Margulies KB, Acker MA, et al. Low Ejection Fraction in Donor Hearts Is Not Directly Associated with Increased Recipient Mortality. Journal of Heart and Lung Transplantation. 2017;(in press). 14. Rao SD, Watson A, Lo P, Jabbour A, Hayward CS, Keogh AM, et al. Successful Orthotropic Heart Transplantation Using Donors With Left Ventricular Systolic Dysfunction: Evidence for Brain Death-Induced Takotsubo Cardiomyopathy. Journal of Heart and Lung Transplantation. 2015;34(4):S71-S2. 15. Dhital KK, Iyer A, Connellan M, Chew HC, Gao L, Doyle A, et al. Adult heart transplantation with distant procurement and ex-vivo preservation of donor hearts after circulatory death: a case series. Lancet. 2015 Jun 27;385(9987):2585-91. PubMed PMID: 25888085. 16. Garcia Saez D, Zych B, Sabashnikov A, Bowles CT, De Robertis F, Mohite PN, et al. Evaluation of the organ care system in heart transplantation with an adverse donor/recipient profile. The Annals of thoracic surgery. 2014 Dec;98(6):2099-105; discussion 105-6. PubMed PMID: 25443013.