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Ann Thorac Surg 1996;62:1731-1736
© 1996 The Society of Thoracic Surgeons
Department of Cardiothoracic Surgery, Cedars-Sinai Medical Center, Los Angeles, California
Accepted for publication May 5, 1996.
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Abstract |
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 TopFootnotes Abstract IntroductionMaterial and MethodsResultsCase ReportsCommentAddendumAcknowledgmentsReferences |
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Methods. A retrospective analysis of 6 patients 70 years of age and older who underwent heart transplantation was done; their clinical courses and outcomes were compared with those of younger patients, with a special emphasis on their posttransplantation quality of life.
Results. All 6 patients are alive and clinically well at a mean follow-up of 12 months. No age-related complications have been observed, and their quality of life is excellent. There has been a very low incidence of rejection, as well as few episodes of rejection.
Conclusions. Heart transplantation in selected people 70 years of age and older can be performed successfully with a morbidity comparable to that seen in younger patients and excellent short-term survival. This initial experience is encouraging, but further studies and long-term follow-up are needed to validate the more routine application of this therapy.
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Introduction |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCase ReportsCommentAddendumAcknowledgmentsReferences |
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For editorial comment, see 1578.
Since the initiation of our heart transplantation program in December 1988, carefully selected patients older than 60 years of age have undergone transplantation for the treatment of end-stage cardiomyopathy not amenable to further medical intervention or conventional cardiac procedures. Among these patients were 6 who were 70 years of age and older. This aggressive approach was taken on the basis of the excellent results obtained in our patient population over the past 4 years, which is reflected by a 100% operative (30 days or to discharge) survival for the last 145 consecutively transplanted patients, with an actuarial survival of 97 ± 1.7 and 93 ± 2.9 at 1 year and 2 years, respectively.
We present our initial experience with 6 septuagenarians who underwent heart transplantation at Cedars-Sinai Medical Center, along with a critical analysis of the lessons learned from this experience.
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Material and Methods |
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These septuagenarians ranged in age from 70 to 77 years (median, 72.8 years) and included 1 woman and 5 men. They were among 22 patients within the same age distribution evaluated for heart transplantation. Four patients presented with end-stage ischemic cardiomyopathy; 3 of them had undergone previous myocardial revascularization (once in 2 patients and three times in the third). Two patients presented with end-stage idiopathic dilated cardiomyopathy. A permanent pacemaker had been implanted in 3 patients, and 2 patients had automatic implantable cardioverter defibrillators. No patient had diabetes mellitus, and 1 patient had arterial hypertension.
The preoperative evaluations performed in these patients were more extensive than those performed in younger patients, and they included assessment of clinical conditions commonly seen in the elderly (ie, prostate, bladder, and colon cancer). A vascular evaluation of carotid and peripheral arteries for the presence of vascular disease was performed, and renal, hepatic, and pulmonary function was thoroughly assessed. An evaluation for significant osteoporosis was also performed. The psychosocial screening of potential candidates was performed by means of numerous personal interviews, including interviews of close family members, by a psychiatrist and a social worker. It included a detailed psychological and behavioral profile, cognitive evaluation, and a detailed history of any drug or substance abuse. The presence of strong family support with total and unrestricted commitment to transplantation was mandatory, as was a local verifiable address. Most importantly, medical and psychosocial compliance and a clear understanding of the diverse implications of transplantation were essential. Patients were considered for transplantation only if they had a positive outlook on life with a high degree of personal and familial satisfaction. Current involvement in a profession or work-related activity was not important. Since, by age definition, these patients are at high risk for transplantation, less-than-optimal evaluation findings indicated exclusion from consideration.
The first patient who received a heart transplant was listed for transplantation as status I, as defined by the United Network for Organ Sharing (UNOS) (ie, on inotropic support or mechanical assist devices, or both, while in the intensive care unit), and the subsequent 5 patients were listed as status II (ie, awaiting transplantation at home).
The donor criteria used were similar to those used for younger patients, although there was a stated willingness to use "high-risk" donors for this group of patients. The local, regional, and distant organ procurement agencies were advised that we would evaluate donor organs that would otherwise be discarded or deemed unsuitable by other transplant programs. This was particularly relevant regarding the height and weight of potential donors, because a high degree of donor/recipient weight mismatch was accepted. Moderate to advanced "undersizing" of donor hearts (eg, donor/recipient weight ratio, 0.8 to 0.5) was possible because all patients presented with normal pulmonary vascular resistance and transpulmonary gradients.
An alternative surgical technique was used for transplantation in these patients, consisting of bicaval and pulmonary venous anastomosis, as previously described [4]. The mean allograft ischemic time was 215 minutes (range, 145 to 262 minutes) with a mean cardiopulmonary bypass time of 92 minutes (range, 62 to 115 minutes). Immunosuppressive therapy for this group of 6 septuagenarians consisted of OKT3 induction therapy (5 mg/day for 7 days), with concomitant administration of cyclosporine (5 mg•kg-1•day-1 for a level of 200 to 400 ng/mL, shown by monoclonal fluorescence polarization immunoassay, within the first 12 weeks after transplantation and for a level of 120 to 200 ng/mL thereafter, started postoperatively once the serum creatinine level was <2.0 mg/dL); azathioprine (4 mg/kg preoperatively and 2 mg•kg-1•day-1 postoperatively, adjusted to the patient's white blood cell count); and steroids (methylprednisolone sodium succinate [Solu-Medrol; Upjohn, Kalamazoo, MI], 1 g at removal of the aortic cross-clamp intraoperatively and then 125 mg intravenously every 8 hours for three doses postoperatively, followed by prednisone [0.25 mg•kg-1•day-1] during OKT3 therapy, increased to 0.5 mg•kg-1•day-1, and then tapered in the subsequent 3 to 8 months). Osteoporosis prophylaxis consisted of calcium carbonate (SmithKline Beecham Pharmaceuticals, Philadelphia, PA), 1.25 g per day; calcitriol (Roche, Nutley, NJ) 0.25 µg daily, and chelated magnesium (Freeda, New York, NY), 1 to 2 g per day, adjusted according to the patient's renal function.
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Results |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCase ReportsCommentAddendumAcknowledgmentsReferences |
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. Although these variables are similar for the two groups of patients, the small sample size of the septuagenarians does not allow for any statistical validation. A low incidence of rejection (one episode of 1B rejection in 1 patient) and of infection (one episode of cytomegalovirus infection in a seronegative patient who received a seropositive allograft) has been documented. All 6 patients have experienced an improved quality of life and have returned to their previous work or social activities.
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Case Reports |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCase ReportsCommentAddendumAcknowledgmentsReferences |
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Patient 2
A 70-year-old, 74-kg woman presented with end-stage ischemic cardiomyopathy with a left ventricular ejection fraction of 0.29. She had undergone coronary revascularization in 1982. Because of the recurrence of angina pectoris with angiographically documented graft closure, the patient underwent repeat myocardial revascularization in 1988 using the left internal mammary artery. Soon thereafter, she underwent her third coronary revascularization, using the right internal mammary artery. Persistent severe angina and a recent acute myocardial infarction prompted the performance of coronary angiography, which showed complete occlusion of all bypass grafts, including both internal mammary arteries. Two-dimensional echocardiography revealed moderate mitral and tricuspid regurgitation. The patient was considered unsuitable for any further myocardial revascularization.
She underwent orthotopic heart transplantation 28 days after being listed for transplantation. The donor was a 49-year-old hypertensive woman who had had a spontaneous hemorrhagic cerebrovascular accident. Although the echocardiogram was normal, a coronary angiogram could not be performed at the donor hospital; therefore the heart was not accepted for transplantation by other transplant programs. The patient had an uneventful postoperative course. Before discharge on her 11th postoperative day, a coronary angiogram was performed (because of the donor's age), which showed no evidence of coronary artery disease.
The patient is clinically well 14 months after transplantation with an excellent quality of life. She has returned to work full-time as a graphic artist. The patient experienced one episode of 1B allograft rejection 1 month after transplantation, which responded to pulse steroid therapy.
Patient 3
A 75-year-old, 77-kg man presented with end-stage ischemic heart disease with a left ventricular ejection fraction of 0.24. He had undergone myocardial revascularization after an acute myocardial infarction with cardiac arrest in 1981. An automatic implantable cardioverter defibrillator was implanted in 1992 because of recurrent episodes of ventricular tachycardia. His cardiac condition deteriorated rapidly over the next 6 months, with multiple episodes of congestive heart failure and repeated discharges from his implanted defibrillator. A permanent VVI pacemaker was implanted in 1993 after atrioventricular node ablation for uncontrollable atrial fibrillation. The patient was considered unsuitable for repeat coronary revascularization because a coronary angiogram had shown patent bypass grafts.
The patient underwent orthotopic heart transplantation 170 days after being listed for transplantation. The donor/recipient weight ratio was 0.65. The donor was a 12-year-old boy who had experienced anoxic brain death after a suicide attempt. Because of the donor's height (152 cm) and weight (50 kg), no local or regional recipients with his blood type (B) were suitable for transplantation. The patient had an uneventful postoperative recovery and was discharged on his 13th postoperative day. The patient has not had any episode of allograft rejection and is clinically well 12 months after transplantation. He has returned part-time to his medical practice and serves on many hospital committees, enjoying an excellent quality of life.
Patient 4
A 71-year-old, 75-kg man presented with end-stage ischemic cardiomyopathy with a left ventricular ejection fraction of 0.15. A coronary cineangiogram showed severe triple-vessel coronary artery disease, but a tomographic myocardial perfusion study showed multiple and diffuse nonreversible ischemic defects throughout the left ventricle. The patient was considered unsuitable for myocardial revascularization.
He underwent orthotopic heart transplantation 71 days after being accepted for transplantation. The donor/recipient weight ratio was 0.50. The donor was a 10-year-old boy involved in a motor vehicle accident. Because of the donor's height (135 cm) and weight (38 kg), there were no local or regional recipients with his blood type (A) suitable for transplantation. The patient had an uneventful postoperative course and was discharged on the 12th postoperative day. He has not experienced any episodes of allograft rejection, although he experienced a mild episode of cytomegalovirus infection 3 months after transplantation that responded to antiviral therapy. The patient is clinically well 11 months after transplantation and enjoys an excellent quality of life. He is actively running his own business on a full-time basis.
Patient 5
A 74-year-old, 71-kg man who had previously undergone mitral valve repair after a 20-year history of mitral valve prolapse presented with severely decompensated end-stage idiopathic dilated cardiomyopathy. His left ventricular ejection fraction was 0.17, with normal coronary arteries shown by cineangiography. He had a permanent pacemaker placed for complete atrioventricular block soon after his mitral valve repair.
The patient underwent orthotopic heart transplantation 22 days after being listed for transplantation. The donor was a 36-year-old hypertensive woman who had sustained a massive spontaneous intracerebral hemorrhage. Two-dimensional echocardiography had shown moderate left ventricular hypertrophy, but she had no history of coronary artery disease. Because of these echocardiographic findings, the donor heart was considered unsuitable for transplantation by all other regional transplant centers.
The patient had an uneventful postoperative course and was discharged on his 11th postoperative day. He has not had any episodes of allograft rejection and is clinically well 8 months after transplantation with an improved quality of life. He is retired from his own business and has resumed his golf and travel activities.
Patient 6
A 70-year-old, 84-kg man presented with severely decompensated end-stage idiopathic cardiomyopathy. His left ventricular ejection fraction was 0.16, with normal coronary arteries shown by cineangiography. The patient underwent orthotopic heart transplantation 87 days after he was listed for transplantation. The donor was a 22-year-old woman who suffered an accidental overdose with amitriptyline hydrochloride, which she was taking for the treatment of postpartum depression. She experienced a prolonged (45 minutes) period of cardiac arrest involving 11 ventricular defibrillation attempts. A two-dimensional echocardiogram revealed mild mitral regurgitation with good wall motion on high doses of inotropic support (22 µg•kg-1•min-1 of dopamine).
Because of the donor's cardiac events at presentation, the heart was considered unsuitable for transplantation by all local and regional transplant centers. The patient had an uncomplicated postoperative course and was discharged on his 11th postoperative day. He has not experienced any episode of allograft rejection and is clinically well 8 months after transplantation. His quality of life is excellent, and he has returned to work as the director of a major film production company.
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Comment |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCase ReportsCommentAddendumAcknowledgmentsReferences |
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Although the efficacy of heart transplantation in patients with end-stage cardiomyopathy is well accepted, its place in the treatment of patients older than 60 years, in contrast to patients receiving kidney or liver transplants, remains unclear for a variety of reasons. First, there is a paucity of clinical reports on this population. Second, the benefit of this expensive medical and surgical intervention in this population is being questioned, given that 15% of the population may then be using up to 70% of the available resources [6]. Third, patients older than 60 years represent a particularly high risk group because of the associated pathologic conditions they may present with. Therefore it is vital to identify any risk factors associated with perioperative events that may influence outcome and quality of life.
In a multicenter study, Bourge and colleagues [7] found that advanced age was, among other risk factors, a pretransplantation risk factor for death after heart transplantation. Their multivariate analysis showed that the expected mortality in patients older than 50 years of age had a progressive increase with age. In addition, the Registry of the International Society for Heart and Lung Transplantation has cited a significant decrease in survival in patients older than 65 years of age at 1, 2, and 3 years after transplantation [1]. In contrast, several studies have shown good results with respect to morbidity and mortality in older patients undergoing cardiac transplantation [8–13]. The investigators in these studies have concluded that advanced age should not be a contraindication to transplantation, provided physiologic age is not advanced by disease of other organ systems, which could limit survival. However, the definition of older age, as reported, is not uniform, as it varies between 50 and 60 years of age [8–13].
A comparison of our results in younger patients with those in patients 60 years of age and older undergoing heart transplantation is shown in Table 2. These encouraging results, including a similar operative mortality, and 1- and 2-year survival and a decreased prevalence of rejection, prompted us to extend the upper age limit of potential recipients. Septuagenarians with end-stage cardiomyopathy who would otherwise meet the selection criteria for heart transplantation, namely, medically refractory cardiac symptoms not amenable to conventional cardiac intervention, have been offered this therapy. Notwithstanding the potential for controversy, this highly selected group of septuagenarians underwent cardiac transplantation in the belief that they could continue to contribute to society. Furthermore, to deny them the benefit of transplantation based solely on the issue of age seemed even more controversial.
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Until more is known about long-term survival and the quality of life in these older transplant recipients, this group of candidates for transplantation should remain on an "alternative list," so that they are not taking donor organs from younger recipients. This consideration was carefully explained to and accepted by these patients and their families who saw transplantation as their only alternative. The decision regarding heart transplantation in these septuagenarians was made in an open discussion with the patients' referring physicians, as well as the entire heart transplantation team, including surgeons, cardiologists, psychiatrists, nurse coordinators, dietitians, social workers, and pharmacists. The medical and ethical issues involved are complex. The idea may not be widely accepted, because it can be argued that this population has the potential to become a burden to society and exhaust the precious resources available. However, we believe that the indications for heart transplantation are constantly evolving, particularly regarding the recipients', as well as the donors', upper age limit. Although no statistical validation can be given to such a small number of patients, this initial experience is encouraging. Short-term results of heart transplantation in this highly select group of septuagenarians indicate they can withstand the rigor of transplantation with improved functional benefit and quality of life. Although no specific test to measure the posttransplantation quality of life (ie, Nottingham health profile or Ferrans' quality of life index) was used in these patients or our younger patients, their subjective description of an improved sense of well-being and physical endurance was clearly observed clinically and was confirmed by their family members. Four of these 6 patients had been previously involved in professional or work-related activities, and they have all returned to these activities. The remaining 2 patients were retired but are also actively involved in multiple family and social activities. In addition, short-term survival has been excellent.
Several lessons were learned from this initial experience. First, the acceptance criteria for cardiac transplantation candidates at this age should be very selective to avert postoperative complications that may not be easily tolerated by older people on immunosuppressive drugs and that would therefore severely affect survival and cost. Second, the criteria for acceptance have been modified so that septuagenarians are only listed for transplantation as status II to minimize perioperative morbidity. Our current practice is not to upgrade these patients to status I if they suffer hemodynamic deterioration. The use of mechanical support or assist devices, or both, as a bridge to transplantation in elderly patients is probably not warranted because they may not be able to tolerate the related complications. If temporary intravenous inotropic support is needed to stabilize cardiac function, their status on the transplant list remains unchanged so that they are not "jumped ahead" of younger patients waiting for transplantation. This group of patients relies on organs deemed unsuitable by other transplant centers on the basis of the donor's weight, a lack of available recipients because of the donor's blood type, or high-risk donors with potentially compromised organs. Third, it appears that these carefully selected patients can withstand the rigor of transplantation and continue to be productive in society. Fourth, although a purely observed phenomenon, a decreased incidence of rejection without a concomitant increase in serious infections has been noticed in these patients. This intriguing aspect of cardiac transplantation in older recipients has been previously reported and, presumably, is a manifestation of decreased immunologic function related to a decline in T-cell function [8]. Such an age-associated decrease in allograft rejection may represent an advantage for elderly individuals who undergo transplantation, which makes this approach increasingly attractive. Immunosuppressive protocols should be tailored to accommodate this decreased immune responsiveness to minimize the incidence of malignant and infectious complications. Fifth, our experience with potentially compromised cardiac allografts seems to confirm that described in previous reports, indicating that the selective use of marginally acceptable organs is compatible with excellent cardiac function and survival [14]. This aggressive approach could alleviate the donor shortage of cardiac transplants by increasing the availability of organs. Finally, our criteria for selecting potential candidates for heart transplantation have evolved so that we evaluate all potential recipients, including select septuagenarians, and identify the risks and benefits in an individual fashion.
It is perhaps the improved hemodynamics stemming from use of the bicaval and pulmonary venous anastomosis technique for allograft implantation that is in part responsible for the excellent cardiac function observed in all these patients after transplantation [15]. Despite the longer allograft ischemic time associated with this technique, we believe its functional advantage, which involves the preservation of the geometric configuration, anatomic size, and physiologic function of the atria, outweighs any potential disadvantages. This alternative approach for heart transplantation has proved, in our experience, to be remarkably simple and safe and has become our routine technique for heart transplantation since October 1991. To date, more than 130 patients have undergone transplantation in this fashion.
Physicians in the future will be pressured to evaluate an increasing number of elderly patients for cardiac transplantation in light of the excellent results obtained in younger patients. Although further studies involving more patients and longer follow-up periods are needed to establish firm recommendations, these early results are encouraging. We recommend that other transplant programs carefully explore the benefits of age-related boundaries in cardiac transplantation and consider older patients, including select septuagenarians, for heart transplantation. This flexible approach would need the establishment of "alternative lists" in organ procurement agencies for these older patients so that the already scarce donor organs would not be shifted away from younger recipients. These bioethical concerns are important, as controversial as they may seem.
Finally, these results must be considered in light of several recent strategies in Congress to reduce health care costs by limiting the availability of medical benefits to the elderly. The decision to ration health care resources will have to take into consideration the fact that the elderly are becoming the fastest-growing and largest segment of the U.S. population, with a decreasing population of younger people [6]. The allocation of sophisticated technology may have to be adjusted as biodemographic changes continue to accelerate. This adjustment may include the reassessment of artificial cut-off points, such as the recipient's upper age limit, in heart transplantation. Despite the difficulties already involved in analyzing the issue of elder care in the present day of health care reform, these results could add significant information to the health care debate regarding costs versus benefits.
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Addendum |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCase ReportsCommentAddendumAcknowledgmentsReferences |
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Acknowledgments |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCase ReportsCommentAddendumAcknowledgmentsReferences |
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Footnotes |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCase ReportsCommentAddendumAcknowledgmentsReferences |
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References |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCase ReportsCommentAddendumAcknowledgmentsReferences |
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90 years of age. Am J Cardiol 1994;74:960–2.[Medline]
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