- Email: [email protected]
Throwing out the good with the bad: Declining potential donor hearts with left ventricular dysfunction
http://www.jhltonline.org
EDITORIAL
Throwing out the good with the bad: Declining potential donor hearts with left ventricular dysfunction Yasbanoo Moayedi, MD,a,b and Kiran K. Khush, MD, MASa From the aDivision of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA; and the bTed Rogers Centre of Excellence in Heart Function, University Health Network, Toronto, Ontario, Canada.
We are currently facing an epidemic of patients surviving end-stage heart failure. Although over 20,000 patients may benefit from heart transplantation per year, only 3,000 will receive a new heart, with a waitlist mortality of 10.7 deaths per 100,000 waitlist-years.1 Due to this growing disparity, we are no longer able to limit acceptance to the “ideal” organ. As such, there has been increased interest in identifying donor risk factors that, although not ideal, still result in acceptable recipient outcomes.2,3 Despite growing evidence supporting the safety of using “marginal” organs, over 60% of available hearts are still being discarded.2 Selecting a suitable donor is a complicated process. Clinicians need to consider multiple factors, weighing recipient urgency against donor characteristics, ischemic time, recipient sensitization and donor/recipient size mismatch.4,5 Unfortunately, we lack guidelines on the management, evaluation and acceptance of marginal organs. These deficiencies have resulted in variable practice patterns between organ procurement organizations and transplant centers across the country, leading to under-utilization of a valuable resource. The most common reason to exclude a donor heart is related to left ventricular dysfunction (LVD) or regional wall motion abnormalities (RWMA) in the absence of a history of heart disease.6 The 2010 guidelines from the International Society for Heart and Lung Transplantation (ISHLT) for the care of heart transplant recipients specifically recommend non-use of a donor heart in the presence of RWMA or the presence of left ventricular ejection fraction (LVEF) o40% despite hemodynamic Reprint requests: Kiran K. Khush, MD, MAS, Division of Cardiovascular Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Falk CVRC 263, Stanford, CA 94305. Telephone: þ650-721-3241. Fax: þ650-725-1599. E-mail address: [email protected]
optimization with inotropic support.7 Although a small proportion of donor hearts may have true cardiomyopathy, LVD and/or RWMA in young donors is most likely related to a “stunned” myocardium.6 Further donor evaluation with inotropic stress testing, serial echocardiograms or a hormonal challenge may be warranted to distinguish a stunned myocardium from irreversible cardiac dysfunction.8,9 More recently, post-transplant recipient outcomes after utilization of donor hearts with LVD were evaluated in a propensity score analysis of the United Network for Organ Sharing (UNOS) database. Patients were grouped according to LVEF as follows: o40%; 40% to 50%; and ≥50%. Odds of primary graft dysfunction and mortality at 1 year were equivalent in all 3 groups.10 Selection bias may have played a role in accepting donor hearts with LVD, as the average donor age in this group was 23 years. Nevertheless, in carefully selected cases, short-term survival results are encouraging. In this issue of the journal, the study by Tryon and colleagues addresses the impact of LVD on donor heart nonutilization in the current era (2007 to 2014), compared with the previous era (1990 to 2006), based on a large UNOS registry analysis.11 In their study, among the discarded organs, 20% were declined exclusively due to LVD; however, of all transplanted hearts, only a small fraction (5%) had LVEF o50%. Their findings show that declined hearts had fewer investigations, and many did not even have a documented LVEF. Furthermore, non-utilization rose from 45% (1990 to 1999) to 60% (2000 to 2007) to 65% (2007 to 2014). Despite the many strengths of their study, a number of important limitations should be considered. First, there are many reasons, in aggregate, for donor heart non-acceptance. It is often a combination of factors, rather than 1 specific reason, that leads to a decision to decline. For example, an elderly patient with multiple medical comorbidities and mild
1053-2498/$ - see front matter r 2017 International Society for Heart and Lung Transplantation. All rights reserved. http://dx.doi.org/10.1016/j.healun.2017.09.009
2
The Journal of Heart and Lung Transplantation, Vol ], No ], Month ]]]]
LVD may fall into a higher donor risk group than a young patient with severe LVD that is likely due to neurogenic stress cardiomyopathy. The refusal codes entered into the deceased donor registration form are often documented in haste, at the time of the organ offer, and may not reflect all of the reasons for donor heart decline. Moreover, the reasons for refusal may be vague (e.g., “quality”) and are often documented by individuals other than the physician making the decision. The analysis by Tryon and colleagues also fails to capture the details of the echocardiographic interpretation of donor heart function. Based on the registry data, the majority of the donor hearts declined either had an LVEF 450% or did not have a documented LVEF. Echocardiographic interpretation of RWMA and LVEF are subject to significant variability, especially when interpreted by individuals who are inexperienced in donor echocardiogram interpretation. Earlier studies have shown significant discrepancies when comparing the interpretation of donor echocardiograms by community readers and experienced echocardiographers at transplant centers.12 In addition, it is not clear which donor hearts in the study had echocardiographic images that were viewed by the transplant centers (and their interpretation) and whether serial testing was performed to guide the decision on whether to accept or decline an organ. Another factor that may influence the acceptance of donor hearts with LVD is the lack of data on long-term recipient outcomes. Although there is an assumption that donor characteristics would preferentially influence shortterm post-transplant outcomes, the paucity of longer term data on survival and graft function may make it difficult to improve non-utilization rates. Finally, the significant rise in donor heart non-utilization in the current era likely corresponds to the increased use of mechanical circulatory support. Clinicians may be conservative in the selection of donor organs for stable patients on a left ventricular assist device, especially in light of strict regulatory scrutiny and monitoring related to 1-year transplant outcomes. Tryon et al should be applauded for systematically attempting to identify donor hearts declined for transplant based on isolated LVD. The authors recognize an important conundrum—that of an alarming non-utilization rate with an ever-growing waitlist, despite evidence showing that donor LVD is often reversible. Although we eagerly await novel biomarkers of reversible cardiomyopathy, standardized donor risk scores, outcomes associated with ex-vivo heart perfusion and donation after cardiac death, immediate and feasible solutions to optimize organ utilization will need to involve the transplant
community on multiple levels. These solutions may include systematic review of declined organs with transplant center feedback, implementation of centralized donor echocardiographic interpretation, removal of institutional penalties for more liberal donor heart acceptance, and implementation of greater rigor in the documentation of declined organs. Prospective studies of donors with LVD are therefore needed to optimize donor management and to improve utilization of these valuable organs.
Disclosure statement The authors have no conflicts of interest to disclose. This study was supported by the National Institutes of Health (Grant R01 HL125303 to K.K.K.).
References 1. Organ Procurement and Transplantation Network. https://optn.trans plant.hrsa.gov/data/view-data-reports/national-data/. Accessed August 1, 2017. 2. Khush KK, Menza R, Nguyen J, et al. Donor predictors of allograft use and recipient outcomes after heart transplantation. Circ Heart Fail 2013;6:300-9. 3. Kransdorf EP, Stehlik J. Donor evaluation in heart transplantation: the end of the beginning. J Heart Lung Transplant 2014;33:1105-13. 4. Nguyen VP, Mahr C, Mokadam NA, et al. The benefit of donorrecipient matching for patients undergoing heart transplantation. J Am Coll Cardiol 2017;69:1707-14. 5. Mehra MR, Canter CE, Hannan MM, et al. The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: a 10year update. J Heart Lung Transplant 2016;35:1-23. 6. Dujardin KS, McCully RB, Wijdicks EF, et al. Myocardial dysfunction associated with brain death: clinical, echocardiographic, and pathologic features. J Heart Lung Transplant 2001;20:350-7. 7. Costanzo MR, Dipchand A, Starling R, et al. The International Society of Heart and Lung Transplantation guidelines for the care of heart transplant recipients. J Heart Lung Transplant 2010;29:914-56. 8. Zaroff JG, Babcock WD, Shiboski SC, et al. Temporal changes in left ventricular systolic function in heart donors: results of serial echocardiography. J Heart Lung Transplant 2003;22:383-8. 9. Bombardini T, Arpesella G, Maccherini M, et al. Medium-term outcome of recipients of marginal donor hearts selected with new stress-echocardiographic techniques over standard criteria. Cardiovasc Ultrasound 2014;12:20. 10. Chen CW, Sprys MH, Gaffey AC, et al. Low ejection fraction in donor hearts is not directly associated with increased recipient mortality. J Heart Lung Transplant 2017;36:611-5. 11. Tryon D, Hasaniya NW, Jabo B, et al. Effect of left ventricular dysfunction on utilization of donor hearts [e-pub ahead of print]. J Heart Lung Transplant. doi: 10.1016/j.healun.2017.07.015, accessed October 4, 2017. 12. Khush KK, Nguyen J, Goldstein BA, et al. Reliability of transthoracic echocardiogram interpretation in potential adult heart transplant donors. J Heart Lung Transplant 2015;34:266-9.
EDITORIAL
Throwing out the good with the bad: Declining potential donor hearts with left ventricular dysfunction Yasbanoo Moayedi, MD,a,b and Kiran K. Khush, MD, MASa From the aDivision of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA; and the bTed Rogers Centre of Excellence in Heart Function, University Health Network, Toronto, Ontario, Canada.
We are currently facing an epidemic of patients surviving end-stage heart failure. Although over 20,000 patients may benefit from heart transplantation per year, only 3,000 will receive a new heart, with a waitlist mortality of 10.7 deaths per 100,000 waitlist-years.1 Due to this growing disparity, we are no longer able to limit acceptance to the “ideal” organ. As such, there has been increased interest in identifying donor risk factors that, although not ideal, still result in acceptable recipient outcomes.2,3 Despite growing evidence supporting the safety of using “marginal” organs, over 60% of available hearts are still being discarded.2 Selecting a suitable donor is a complicated process. Clinicians need to consider multiple factors, weighing recipient urgency against donor characteristics, ischemic time, recipient sensitization and donor/recipient size mismatch.4,5 Unfortunately, we lack guidelines on the management, evaluation and acceptance of marginal organs. These deficiencies have resulted in variable practice patterns between organ procurement organizations and transplant centers across the country, leading to under-utilization of a valuable resource. The most common reason to exclude a donor heart is related to left ventricular dysfunction (LVD) or regional wall motion abnormalities (RWMA) in the absence of a history of heart disease.6 The 2010 guidelines from the International Society for Heart and Lung Transplantation (ISHLT) for the care of heart transplant recipients specifically recommend non-use of a donor heart in the presence of RWMA or the presence of left ventricular ejection fraction (LVEF) o40% despite hemodynamic Reprint requests: Kiran K. Khush, MD, MAS, Division of Cardiovascular Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Falk CVRC 263, Stanford, CA 94305. Telephone: þ650-721-3241. Fax: þ650-725-1599. E-mail address: [email protected]
optimization with inotropic support.7 Although a small proportion of donor hearts may have true cardiomyopathy, LVD and/or RWMA in young donors is most likely related to a “stunned” myocardium.6 Further donor evaluation with inotropic stress testing, serial echocardiograms or a hormonal challenge may be warranted to distinguish a stunned myocardium from irreversible cardiac dysfunction.8,9 More recently, post-transplant recipient outcomes after utilization of donor hearts with LVD were evaluated in a propensity score analysis of the United Network for Organ Sharing (UNOS) database. Patients were grouped according to LVEF as follows: o40%; 40% to 50%; and ≥50%. Odds of primary graft dysfunction and mortality at 1 year were equivalent in all 3 groups.10 Selection bias may have played a role in accepting donor hearts with LVD, as the average donor age in this group was 23 years. Nevertheless, in carefully selected cases, short-term survival results are encouraging. In this issue of the journal, the study by Tryon and colleagues addresses the impact of LVD on donor heart nonutilization in the current era (2007 to 2014), compared with the previous era (1990 to 2006), based on a large UNOS registry analysis.11 In their study, among the discarded organs, 20% were declined exclusively due to LVD; however, of all transplanted hearts, only a small fraction (5%) had LVEF o50%. Their findings show that declined hearts had fewer investigations, and many did not even have a documented LVEF. Furthermore, non-utilization rose from 45% (1990 to 1999) to 60% (2000 to 2007) to 65% (2007 to 2014). Despite the many strengths of their study, a number of important limitations should be considered. First, there are many reasons, in aggregate, for donor heart non-acceptance. It is often a combination of factors, rather than 1 specific reason, that leads to a decision to decline. For example, an elderly patient with multiple medical comorbidities and mild
1053-2498/$ - see front matter r 2017 International Society for Heart and Lung Transplantation. All rights reserved. http://dx.doi.org/10.1016/j.healun.2017.09.009
2
The Journal of Heart and Lung Transplantation, Vol ], No ], Month ]]]]
LVD may fall into a higher donor risk group than a young patient with severe LVD that is likely due to neurogenic stress cardiomyopathy. The refusal codes entered into the deceased donor registration form are often documented in haste, at the time of the organ offer, and may not reflect all of the reasons for donor heart decline. Moreover, the reasons for refusal may be vague (e.g., “quality”) and are often documented by individuals other than the physician making the decision. The analysis by Tryon and colleagues also fails to capture the details of the echocardiographic interpretation of donor heart function. Based on the registry data, the majority of the donor hearts declined either had an LVEF 450% or did not have a documented LVEF. Echocardiographic interpretation of RWMA and LVEF are subject to significant variability, especially when interpreted by individuals who are inexperienced in donor echocardiogram interpretation. Earlier studies have shown significant discrepancies when comparing the interpretation of donor echocardiograms by community readers and experienced echocardiographers at transplant centers.12 In addition, it is not clear which donor hearts in the study had echocardiographic images that were viewed by the transplant centers (and their interpretation) and whether serial testing was performed to guide the decision on whether to accept or decline an organ. Another factor that may influence the acceptance of donor hearts with LVD is the lack of data on long-term recipient outcomes. Although there is an assumption that donor characteristics would preferentially influence shortterm post-transplant outcomes, the paucity of longer term data on survival and graft function may make it difficult to improve non-utilization rates. Finally, the significant rise in donor heart non-utilization in the current era likely corresponds to the increased use of mechanical circulatory support. Clinicians may be conservative in the selection of donor organs for stable patients on a left ventricular assist device, especially in light of strict regulatory scrutiny and monitoring related to 1-year transplant outcomes. Tryon et al should be applauded for systematically attempting to identify donor hearts declined for transplant based on isolated LVD. The authors recognize an important conundrum—that of an alarming non-utilization rate with an ever-growing waitlist, despite evidence showing that donor LVD is often reversible. Although we eagerly await novel biomarkers of reversible cardiomyopathy, standardized donor risk scores, outcomes associated with ex-vivo heart perfusion and donation after cardiac death, immediate and feasible solutions to optimize organ utilization will need to involve the transplant
community on multiple levels. These solutions may include systematic review of declined organs with transplant center feedback, implementation of centralized donor echocardiographic interpretation, removal of institutional penalties for more liberal donor heart acceptance, and implementation of greater rigor in the documentation of declined organs. Prospective studies of donors with LVD are therefore needed to optimize donor management and to improve utilization of these valuable organs.
Disclosure statement The authors have no conflicts of interest to disclose. This study was supported by the National Institutes of Health (Grant R01 HL125303 to K.K.K.).
References 1. Organ Procurement and Transplantation Network. https://optn.trans plant.hrsa.gov/data/view-data-reports/national-data/. Accessed August 1, 2017. 2. Khush KK, Menza R, Nguyen J, et al. Donor predictors of allograft use and recipient outcomes after heart transplantation. Circ Heart Fail 2013;6:300-9. 3. Kransdorf EP, Stehlik J. Donor evaluation in heart transplantation: the end of the beginning. J Heart Lung Transplant 2014;33:1105-13. 4. Nguyen VP, Mahr C, Mokadam NA, et al. The benefit of donorrecipient matching for patients undergoing heart transplantation. J Am Coll Cardiol 2017;69:1707-14. 5. Mehra MR, Canter CE, Hannan MM, et al. The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: a 10year update. J Heart Lung Transplant 2016;35:1-23. 6. Dujardin KS, McCully RB, Wijdicks EF, et al. Myocardial dysfunction associated with brain death: clinical, echocardiographic, and pathologic features. J Heart Lung Transplant 2001;20:350-7. 7. Costanzo MR, Dipchand A, Starling R, et al. The International Society of Heart and Lung Transplantation guidelines for the care of heart transplant recipients. J Heart Lung Transplant 2010;29:914-56. 8. Zaroff JG, Babcock WD, Shiboski SC, et al. Temporal changes in left ventricular systolic function in heart donors: results of serial echocardiography. J Heart Lung Transplant 2003;22:383-8. 9. Bombardini T, Arpesella G, Maccherini M, et al. Medium-term outcome of recipients of marginal donor hearts selected with new stress-echocardiographic techniques over standard criteria. Cardiovasc Ultrasound 2014;12:20. 10. Chen CW, Sprys MH, Gaffey AC, et al. Low ejection fraction in donor hearts is not directly associated with increased recipient mortality. J Heart Lung Transplant 2017;36:611-5. 11. Tryon D, Hasaniya NW, Jabo B, et al. Effect of left ventricular dysfunction on utilization of donor hearts [e-pub ahead of print]. J Heart Lung Transplant. doi: 10.1016/j.healun.2017.07.015, accessed October 4, 2017. 12. Khush KK, Nguyen J, Goldstein BA, et al. Reliability of transthoracic echocardiogram interpretation in potential adult heart transplant donors. J Heart Lung Transplant 2015;34:266-9.