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Cardiac Transplantation after 60 Years of Age
EDITORIAL
Cardiac Transplantation after 60 Years of Age Jack G. Copeland, M.D. In the twenty years that have passed since the first human-to-human cardiac transplant, and particularly since the widespread use of cyclosporine in 1983, cardiac transplantation under the proper circumstances has become an accepted therapy for selected patients with endstage heart disease. Recipient selection criteria, which in the early 1970s were necessarily strict reflecting a desire to demonstrate to the skeptical world the efficacy of the procedure, have broadened in the 1980s. Limits for candidate selection are now to some extent determined by donor supplyhecipient demand ratio; local, regional, and national affluence; and the personal philosophies of program directors, as well as the standard set of ”modified Stanford exclusion criteria,” now best exemplified in the ”Criteria for Medicare Coverage of Heart Transplants” [l]. The paper of Frazier and colleagues in this issue of The Annuls, which demonstrates short-term success with cardiac transplantation in patients over 60 years of age, is pertinent to the debate over what has been the most discussed selection criterion, recipient age. In the late 1960s and early 1970s, cardiac transplantation was believed to be contraindicated in patients over 50 years of age, based on data which revealed a significant survival advantage of younger recipients [2]. The current Medicare selection criteria set 57 years as the upper age limit, citing greater expected mortality in older patients. The Registry of the International Society for Heart Transplantation shows a 30-day mortality of 9.4% for ages 60 to 64 and 16.7% for those 65 and over [3]. Therefore, the 12-month actuarial survival rate of 83% reported by Frazier for patients over 60 years of age is an excellent early result. Undoubtedly the outlook has been improved by triple-therapy immunosuppression (cyclosporine, azathioprine, prednisone). But, as the authors suggest, perhaps older patients have less immune responsiveness and thus constitute a favorable group requiring less immunosuppression. A quantitative comparison of immunosuppressive regimens might have added credence to this theory. There was no difference in infection rates between younger and older patients. Mortality from infection has decreased in the cyclosporine era, and this in our experience seems to be related not only to aggressive diagnosis and treatment with new antimicrobials, but also to the use of multidrug therapy that has permitted considerable reductions in the doses of both steroids and cyclosporine. Finally, the authors suggest, as others did in the precyclosporine era, that a history of multiple transfusions bestowed some degree of immunotolerance. This “advantage” is From the Department of Surgery, The University of Arizona Health Sciences Center, Tucson, AZ 85724.
well known in renal transplantation; however, since the advent of cyclosporine use in cardiac recipients, it has not been a significant determinant of outcome. The fine results at 12 months’ mean follow-up would seem to open cardiac transplantation to a large pool of candidates, thereby accentuating the current donor heart shortage. The short-term evaluation, however, is an inadequate assessment of the procedure in this age group if one admits that, in addition to the immediate salvage of life, we are also interested in attaining maximal duration of function from each donor heart. Our data for recipients over 50 years old demonstrate identical survival in the group of recipients under 50 years old for the initial two years, followed in the third year by a significant drop in survival of the older group [4]. Mortality in older transplant recipients is often not related to either infection or rejection, but to other processes, e.g., cerebrovascular, gastrointestinal, pulmonary, or renal disease, or to malignancies present at the time of transplantation or thereafter. Another limitation of the current report and others dealing with this subject is that it does not formally address selection criteria in the 60 and over age group. Are these patients different from those in younger groups? They certainly are in my and my colleagues’ experience. For instance, my colleagues and I would not attempt transplantation in an elderly patient requiring Jarvik heart implantation (nor would we implant a Jarvik heart), but we have done this in 6 younger bridge-totransplant patients, 3 of whom are alive and well after transplantation. We also recognize that natural selection plays a role in determining which elderly patients.are referred. The size of the pool of reasonable candidates over 60 may not be too large. It represented 14% in Frazier’s experience, 2.6% (4152) in ours, and 1.6% in the world experience. This paper raises some other questions relating to the acceptance of older recipients potentiating the critical donor heart shortage. First, How does one establish priority on the waiting list for the older recipient? Should he or she be penalized for being older? We have not imposed a penalty, but have attempted to be highly selective in choosing candidates. Because of the increasing size of our potential cardiac recipient list, we have adopted the Pittsburgh system which gives points for time on the list, degree of illness, and positive cytotoxic screen. Second, without having done so, the authors suggest using donor hearts from older donors, or using “undesirable” donor hearts in the older recipient. Is it ethical to use a donor heart which increases the recipient’s risk? It would seem to me that using a compromised donor organ would not only decrease survival rates, but also limit the functional and long-term results.
115 Ann Thorac Surg 45:115-116, Feb 1988. Copyright 0 1988 by The Society of Thoracic Surgeons
116 The Annals of Thoracic Surgery Vol 45 No 2 February 1988
The high human and financial cost of the procedure does not justify this approach. Finally, one must ask whether this is not the age group for which the totally implantable assist device is the best answer. In 2 to 3 years, when total implantability is possible with a left ventricular assist system (Novacor),the elderly myopath might be considered a reasonable candidate. In summary, the data from Frazier and colleagues and from others indicate that we should not arbitrarily withhold cardiac transplantation on the basis of age. It reemphasizes the dilemma caused by increased demand for costly technology and scarce resources that faces the modern era of cardiac transplantation, and it raises the philosophical question at this time of severe donor
shortage: Should we give priority to the sickest and the oldest or to those with the best chance for survival?
References 1. Medicare Program: Criteria for Medicare Coverage of Heart Transplants. Federal Register 46:10935, 1987 2. Copeland JG, Stinson EB: Human heart transplantation. Curr Probl Cardiol 4:1, 1979 3. Kay MP: The Registry of the International Society for Heart Transplantation: fourth official report-1987. Heart Transplantation 1987;6:63 4. Carrier M, Emery RW, Riley JE, et al: Cardiac transplantation in patients over the age of 50 years. J Am Coll Cardiol8:285, 1986
Cardiac Transplantation after 60 Years of Age Jack G. Copeland, M.D. In the twenty years that have passed since the first human-to-human cardiac transplant, and particularly since the widespread use of cyclosporine in 1983, cardiac transplantation under the proper circumstances has become an accepted therapy for selected patients with endstage heart disease. Recipient selection criteria, which in the early 1970s were necessarily strict reflecting a desire to demonstrate to the skeptical world the efficacy of the procedure, have broadened in the 1980s. Limits for candidate selection are now to some extent determined by donor supplyhecipient demand ratio; local, regional, and national affluence; and the personal philosophies of program directors, as well as the standard set of ”modified Stanford exclusion criteria,” now best exemplified in the ”Criteria for Medicare Coverage of Heart Transplants” [l]. The paper of Frazier and colleagues in this issue of The Annuls, which demonstrates short-term success with cardiac transplantation in patients over 60 years of age, is pertinent to the debate over what has been the most discussed selection criterion, recipient age. In the late 1960s and early 1970s, cardiac transplantation was believed to be contraindicated in patients over 50 years of age, based on data which revealed a significant survival advantage of younger recipients [2]. The current Medicare selection criteria set 57 years as the upper age limit, citing greater expected mortality in older patients. The Registry of the International Society for Heart Transplantation shows a 30-day mortality of 9.4% for ages 60 to 64 and 16.7% for those 65 and over [3]. Therefore, the 12-month actuarial survival rate of 83% reported by Frazier for patients over 60 years of age is an excellent early result. Undoubtedly the outlook has been improved by triple-therapy immunosuppression (cyclosporine, azathioprine, prednisone). But, as the authors suggest, perhaps older patients have less immune responsiveness and thus constitute a favorable group requiring less immunosuppression. A quantitative comparison of immunosuppressive regimens might have added credence to this theory. There was no difference in infection rates between younger and older patients. Mortality from infection has decreased in the cyclosporine era, and this in our experience seems to be related not only to aggressive diagnosis and treatment with new antimicrobials, but also to the use of multidrug therapy that has permitted considerable reductions in the doses of both steroids and cyclosporine. Finally, the authors suggest, as others did in the precyclosporine era, that a history of multiple transfusions bestowed some degree of immunotolerance. This “advantage” is From the Department of Surgery, The University of Arizona Health Sciences Center, Tucson, AZ 85724.
well known in renal transplantation; however, since the advent of cyclosporine use in cardiac recipients, it has not been a significant determinant of outcome. The fine results at 12 months’ mean follow-up would seem to open cardiac transplantation to a large pool of candidates, thereby accentuating the current donor heart shortage. The short-term evaluation, however, is an inadequate assessment of the procedure in this age group if one admits that, in addition to the immediate salvage of life, we are also interested in attaining maximal duration of function from each donor heart. Our data for recipients over 50 years old demonstrate identical survival in the group of recipients under 50 years old for the initial two years, followed in the third year by a significant drop in survival of the older group [4]. Mortality in older transplant recipients is often not related to either infection or rejection, but to other processes, e.g., cerebrovascular, gastrointestinal, pulmonary, or renal disease, or to malignancies present at the time of transplantation or thereafter. Another limitation of the current report and others dealing with this subject is that it does not formally address selection criteria in the 60 and over age group. Are these patients different from those in younger groups? They certainly are in my and my colleagues’ experience. For instance, my colleagues and I would not attempt transplantation in an elderly patient requiring Jarvik heart implantation (nor would we implant a Jarvik heart), but we have done this in 6 younger bridge-totransplant patients, 3 of whom are alive and well after transplantation. We also recognize that natural selection plays a role in determining which elderly patients.are referred. The size of the pool of reasonable candidates over 60 may not be too large. It represented 14% in Frazier’s experience, 2.6% (4152) in ours, and 1.6% in the world experience. This paper raises some other questions relating to the acceptance of older recipients potentiating the critical donor heart shortage. First, How does one establish priority on the waiting list for the older recipient? Should he or she be penalized for being older? We have not imposed a penalty, but have attempted to be highly selective in choosing candidates. Because of the increasing size of our potential cardiac recipient list, we have adopted the Pittsburgh system which gives points for time on the list, degree of illness, and positive cytotoxic screen. Second, without having done so, the authors suggest using donor hearts from older donors, or using “undesirable” donor hearts in the older recipient. Is it ethical to use a donor heart which increases the recipient’s risk? It would seem to me that using a compromised donor organ would not only decrease survival rates, but also limit the functional and long-term results.
115 Ann Thorac Surg 45:115-116, Feb 1988. Copyright 0 1988 by The Society of Thoracic Surgeons
116 The Annals of Thoracic Surgery Vol 45 No 2 February 1988
The high human and financial cost of the procedure does not justify this approach. Finally, one must ask whether this is not the age group for which the totally implantable assist device is the best answer. In 2 to 3 years, when total implantability is possible with a left ventricular assist system (Novacor),the elderly myopath might be considered a reasonable candidate. In summary, the data from Frazier and colleagues and from others indicate that we should not arbitrarily withhold cardiac transplantation on the basis of age. It reemphasizes the dilemma caused by increased demand for costly technology and scarce resources that faces the modern era of cardiac transplantation, and it raises the philosophical question at this time of severe donor
shortage: Should we give priority to the sickest and the oldest or to those with the best chance for survival?
References 1. Medicare Program: Criteria for Medicare Coverage of Heart Transplants. Federal Register 46:10935, 1987 2. Copeland JG, Stinson EB: Human heart transplantation. Curr Probl Cardiol 4:1, 1979 3. Kay MP: The Registry of the International Society for Heart Transplantation: fourth official report-1987. Heart Transplantation 1987;6:63 4. Carrier M, Emery RW, Riley JE, et al: Cardiac transplantation in patients over the age of 50 years. J Am Coll Cardiol8:285, 1986