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Cardiac transplantation in the seventh decade of life
Cardiac Transplantation in the Seventh Decade of Life Dan J. Aravot, MD, Nicholas R. Banner, MRCP, Asghar Khaghani, FRCS, Melissa Fitzgerald, MB, BS, Rosemary Radley-Smith, FRCP, Andrew G. Mitchell, MRCP, and Magdi H. Yacoub, FRCS
Twenty-five patients older than 60 years of age underwent cardiac transplantation using an immunosuppression protocol with cyclosporin and azathioprine, but without routine use of oral steroids. There were 24 men and 1 woman (age range 60 to 69 years, mean 63). The etiology of heart disease was coronary artery disease in 21 and idiopathic dilated cardiomyopathy in 4. Six patients had previous coronary artery bypass operations, 1 had undergone repair of an abdominal aneurysm and 1 had pulmonary embolism. Sixteen patients were in New York Heart Association class IV and 9 in class Ill. Donor mean age was 30 (14 to 46) years. Hospital stay after transplantation was 10 to 90 days (median 11). Four died within 30 days and none from 5 to 59 months (mean 22). The l-year actuarial survival was 84%. The incidence of rejection was 2.16 episodes per patient. Only 1 patient (4%) had serious infection. Six patients received antihypertensive treatment, 3 had reversible impairment of renal function, 2 had gout and 1 had drop foot. No patient had convulsions, transient ischemic attack or cerebrovascular accident. None had significant psychological problems. The 21 patients currently alive are in New York Heart Association class I. Quality of life, assessed by the Nottingham Health Profile, showed marked improvement. It is concluded that the initial results of cardiac transplantation in the seventh decade of life are encouraging. (Am J Cardiol 1989;63:90-93)
From the Harefield Hospital, Harefield, Middlesex, England. Manuscript receivedJuly 26, 1988;revised manuscript received September 6, 1988,and acceptedSeptember 11. Address for reprints: M.H. Yacoub, FRCS, Harefield Hospital, Harefield, Middlesex UB9 6JH, England.
90
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 63
ardiac transplantation is now becomingan accepted form of treatment for end-stagecardiac failure.’ During the current decadethere has beena marked improvement in the results obtained, partly due to the introduction of cyclosporin.2y3This, in turn, has been associatedwith a rapid increase in the number of transplants performed at our hospital4 and other centers.5At the sametime there has been a gradual relaxation of the criteria for potential transplant recipients.‘j Before the introduction of cyclosporin, when corticosteroids were the principal form of immunosuppression, older patients were considered poor candidates for transplantation.7 Since September 1982 we have used an immunosuppressiveregimen that does not include routine use of oral corticosteroids.8The present report covers our experience with 25 patients who underwent cardiac transplantation in their seventh decadeof life using a cyclosporin/azathioprine regimen betweenJune 1983 and January 1988.
C
METHODS During a period of 8 years, 500 patients have undergone cardiac transplantation at Harefield Hospital. The proceduresincluded 460 orthotopic, 36 heterotopic and 4 combined orthotopic and heterotopic transplants. Three patients have undergone orthotopic retransplantation. Our selection policy for transplantation has been describedpreviously.4The age distribution of the recipients ranged from 9 days to 69 years (Figure 1). The twenty-five patients who were in their seventh decadeof life included 24 men and 1 woman (mean age 63 years, range 60 to 69). Before transplantation, 16 patients were in New York Heart Association class IV and 9 in class III. The etiology of their cardiac failure was coronary artery diseasein 21 (84%) patients (compared with 53% overall in our transplant recipients4) and idiopathicdilated cardiomyopathy in 4 (16%). Seven patients (29%) had undergone previous major surgery (6 had open heart surgery and 1 had repair of abdominal aneurysm). One patient had sustaineda recent pulmonary embolism. Diabetic retinopathy or nephropathy, cerebrovascular diseaseand intrinsic renal or hepatic diseasewere consideredto be contraindications to transplantation. Donors were matched according to ABO compatibility and recipient’s body size. The donors’ mean age was 30 (range 14 to 46) years. All the hearts were harvested
at the donors’ hospitals and preservedwith St. Thomas’ cardioplegic solution. Total ischemic time ranged from 73 to 245 (mean 148) minutes. Nineteen recipients underwent orthotopic cardiac transplantation performed with the conventional technique of Lower and Shumway9and 6 with a new technique, developedat our hospital, in which the systemic and pulmonary veins are anastomosedleaving the donor atria intact. All patients were managedwith an immunosuppressiveprotocol that consisted of cyclosporin and azathioprine without the routine use of oral steroids.* Cyclosporin (2 to 10 mg/ kg) and azathioprine (2 mg/kg) were given preoperatively with the anesthetic premeditation and 1 g of methylprednisolone was administered intraoperatively after releasing the aortic clamp. After transplantation, the recipients continued receiving cyclosporin administered twice daily in dosesvarying between 2 and 20 mg/kg/day and adjusted according to the trough plasma level (determined by a polyspecific radioimmunoassay) and renal function, The target levels were 400 ng/ ml during the first month and 100 to 200 rig/ml subsequently. Azathioprine was given in a dose of 2 mg/kg/ day (which was reduced if the patient’s white count decreasedbelow 3.5 log/liter). Recipients were monitored for rejection as previously describede4Acute cardiac rejection, diagnosed histologically, was usually treated with either pulse dosesof intravenous methylprednisolone (1 g daily for 3 days), antithymocyte globulin, a combination of the 2 agents or with monoclonal antibodies (depending on the severity of rejection).
20
0 0
Early results: The mean stay at the intensive care unit and the median hospital stay after cardiac transplantation were 1.7 days (range 1 to 5) and 11 days (range 10 to 90), respectively. There were 4 early deaths (within 1 month), 2 from acute rejection and 2 from multiorgan failure. The mean number of rejection episodesper patient was 2.1. Only 1 patient experienced a seriousinfection (empyema of right chest after a preoperativepulmonary embolism) and recoveredfollowing 200 T
90
No at Risk:
RESULTS
25
20
180 Time
270 360 450 after transplantation
19
PtGURE 2. Actuarial survival in the seventh decade of life.
540 (Days)
630
720 6
15
of cardiac transplant
recipients
100
80
Before TX a After TX
I
Age
IGURE 1. Age distribution lant recipients at Harefield
treatment with antibiotics and decortication. Three patients had reversible impairment of renal function, which was successfullytreated by temporarily substituting steroids for cyclosporin. Two patients developed gout and 1 foot drop which improved with intensive physiotherapy. None of the recipients suffered convulsions, transient ischemic attacks or cerebrovascular accidents. None had significant psychological problems. “Late” results: There were no late deaths during a follow-up period extending from 5 to 59 months (mean 22). Six patients required antihypertensive treatment. The l-year actuarial survival was 84% (Figure 2). The 21 patients currently alive are all in New York Heart Association class I. Quality of life, assessedby the Nottingham Health Profile, 10 showed reduction in scores for all dimensions corresponding to a reduction in symp-
(years)
of 500 con Hospital.
ive cardiac brans-
dimensions in part 1 of the IGURE 3. Mean scores for the Nottingham Health Profile before transplantation (lx) and 6 months after it.
THE AMERICAN JOURNAL OF CARDIOLOGY JANUARY 1. 1989
CARDIAC
TRANSPLANTATION
IN SEVENTH
DECADE
25
0 0 0 0
200
FIGURE 4. Maximal workload, oxygen uptake, heart rate and ventilation achieved during symptom-limited graded exercise on a cycle ergometer.
T
B
175~-
0 2 rP r
150~-
:: 2
0 0 0 0 0 0 0
125~loo-
0
0
0 0
0 0
0 0
0 0
0
75 i
toms and perceived health problems (Figure 3). The results of the most recent cardiopulmonary exercise tests (performed at a mean of 6 months after transplantation) are shown in Figure 4. Due to cardiac denervation, peak heart rates based on the age of the patient were lower than predicted. Peak oxygen uptake was also lower than predicted,l1 but sufficient to allow a good level of rehabilitation in all patients. Long-term survivors underwent coronary angiography at annual intervals after transplantation. Only 1 of 19 patients has been found to have angiographically evident coronary artery diseasein the transplanted heart (which was of moderate severity and was demonstrated 1 year after operation). This patient is currently asymptomatic and with no evidence of diseaseprogression or left ventricular function deterioration. He is currently under observation and has not been considered for retransplantation.
The length of hospitalization and cost of cardiac transplantation for our patients was similar to those for younger patients at our hospital. The quality of life and degreeof rehabilitation achievedby thesepatients after transplantation was good. The incidence of coronary artery disease (5.3% at 1 year) is similar to our overall experience in cardiac transplant recipients treated with cyclosporin and azathioprine without the routine use of corticosteroids (3% at 1 year).4 Successfulcardiac transplantation in this age group greatly increasesthe number of potential cardiac transplantation candidates becauseof the high incidence of coronary artery diseasein Western societies.Already, recipients in the sixth decadeof life comprisethe second largest group in our program (Figure 1). The scarce supply of donor organs limits the activity of cardiac transplant programs.14J5It appearsthat this will be the main factor among the restrictions for cardiac transplantation in the older patients.6,7There are many factors influencing the supply of donor organs that are beyond the control of individual cardiac transplantation units.14 However, measuressuch as extending age range for potential cardiac donors and using hearts from heart and lung transplant recipients4may help to alleviate this problem.
DISCUSSION Our results demonstrate that cardiac transplantation can be performed in the seventh decadeof life with survival rates as well as frequency of rejection and complication rates that are similar to those seen in younger age groups. We believe the low incidence of infection in our serieswas probably due to the avoidance of routine oral steroids combined with the use of prophylactic antibiotics and acyclovir. 12J3Only 1 serious infection oc- REFERENCES 1. Griffith BP, Hardesty RL, Trento A, Kormos RL, Bahnson HT. Cardiac curred in this age group (incidence 4%) compared with transplantation-emerging from an experiment to service. Ann Surg 1986; 5.2% in a consecutive seriesof 96 cardiac transplant re- 204:308-314. cipients at our hospital.13The incidence of rejection (2.1 2. Levett JM, Karp RB. Heart transplantation. Surg Clin North Am 1985; episodesper patient) is similar to our general experience 65:613-635. 3. Kahan BD. Immunosuppressive therapy with cyclosporin for cardiac trans(1.8 episodesin the first 3 months after operation.)8 The plantation. Circulation 1987:75:40-56. incidence of other complications that might be expected 4. Banner NR, Fitzgerald M, Khaghani A, Aravot D, Reid C, Mitchell AG, Radley Smith R, Yacoub MH. Cardiac transplantationat Harefield Hospital. In: in elderly patients such as renal failure, hypertension Terasaki P, ed. Clinical Transplants 1987. Los Angeles: UCLA Tissue Typing Laboratory, 1987:17-26. and cerebral events was not increased in this series.
92
THE AMERICAN JOURNAL OF CARDIOLOGY
VOLUME 63
5. Kaye MP. The Registry of the International Society for Heart Transplantation: fourth official report--1987. In: Terasaki P, ed. Clinical Transplants 1987. Las Angeles: ULCA Tissue Typing Laboratory, 1987:1-6. 6. Copeland JG, Emery RW, Levinson MM, Icenogle TB, Carrier M, Olt RA, Copeland JA, McAleer-Rhenman MJ, Nicholson SM. Selection of patients for cardiac transplantation. Circulation 1987;75;2-9. 7. Szentpelery S, Thames M, Hanrahan J, Morris J, Lower RR. Cardiac transplantation in the sixth decade of life. Transplant Pmc /987;19:2492-2494. 8. Yacoub M, Alivizatos P, Khaghani A, Mitchell A. The use of cyclosporin, azathioprine and antithymocyte globulin with or without low dose steroids for immunosuppression of cardiac transplantation. Transplant Proc 1985;17:221~ 222. 9. Lower RR, Shumway NE. Studies on orthotopic homotransplantation of the canine heart. Surg Forum 1960;11:18-19.
10. Hunt SM, McEwen .I. The development of a subjective health indicator Health IIlness 19X%2:231 -245. 11. Jones NL, Campbell EJM. Clinical Exercise Testing. Philadelphia: WB Saunders, 1982,249. 12. Ashraf MH, Campalani GC, Qureshi SA, Fraud DJ, Yacoub MH. Acyclovir in treatment of cytomegalovirus pneumonia after cardiac transplantation. Lam% 1982:1:173-174. 13. Khaghani A, Martin M, Fitzgerald M, Skacel M, Aravot D, Yacoub MH. Cefotaxime and tlucloxacillin as antibiotic prophylaxis in cardiac transplantation. Drugs 1988;35(suppl2):124-126. 14. Robertson JA. Supply and distribution of hearts for transplantation: legal, ethical and policy issues. Circulation 1987;7.5:77-87. 15. Casscells W. Heart transplantation-recent policy developments. N Engl J Med 1986:3lS:1365-1368.
Sociof
THE AMERICAN JOURNAL OF CARDIOLOGY JANUARY 1, 1989
Twenty-five patients older than 60 years of age underwent cardiac transplantation using an immunosuppression protocol with cyclosporin and azathioprine, but without routine use of oral steroids. There were 24 men and 1 woman (age range 60 to 69 years, mean 63). The etiology of heart disease was coronary artery disease in 21 and idiopathic dilated cardiomyopathy in 4. Six patients had previous coronary artery bypass operations, 1 had undergone repair of an abdominal aneurysm and 1 had pulmonary embolism. Sixteen patients were in New York Heart Association class IV and 9 in class Ill. Donor mean age was 30 (14 to 46) years. Hospital stay after transplantation was 10 to 90 days (median 11). Four died within 30 days and none from 5 to 59 months (mean 22). The l-year actuarial survival was 84%. The incidence of rejection was 2.16 episodes per patient. Only 1 patient (4%) had serious infection. Six patients received antihypertensive treatment, 3 had reversible impairment of renal function, 2 had gout and 1 had drop foot. No patient had convulsions, transient ischemic attack or cerebrovascular accident. None had significant psychological problems. The 21 patients currently alive are in New York Heart Association class I. Quality of life, assessed by the Nottingham Health Profile, showed marked improvement. It is concluded that the initial results of cardiac transplantation in the seventh decade of life are encouraging. (Am J Cardiol 1989;63:90-93)
From the Harefield Hospital, Harefield, Middlesex, England. Manuscript receivedJuly 26, 1988;revised manuscript received September 6, 1988,and acceptedSeptember 11. Address for reprints: M.H. Yacoub, FRCS, Harefield Hospital, Harefield, Middlesex UB9 6JH, England.
90
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 63
ardiac transplantation is now becomingan accepted form of treatment for end-stagecardiac failure.’ During the current decadethere has beena marked improvement in the results obtained, partly due to the introduction of cyclosporin.2y3This, in turn, has been associatedwith a rapid increase in the number of transplants performed at our hospital4 and other centers.5At the sametime there has been a gradual relaxation of the criteria for potential transplant recipients.‘j Before the introduction of cyclosporin, when corticosteroids were the principal form of immunosuppression, older patients were considered poor candidates for transplantation.7 Since September 1982 we have used an immunosuppressiveregimen that does not include routine use of oral corticosteroids.8The present report covers our experience with 25 patients who underwent cardiac transplantation in their seventh decadeof life using a cyclosporin/azathioprine regimen betweenJune 1983 and January 1988.
C
METHODS During a period of 8 years, 500 patients have undergone cardiac transplantation at Harefield Hospital. The proceduresincluded 460 orthotopic, 36 heterotopic and 4 combined orthotopic and heterotopic transplants. Three patients have undergone orthotopic retransplantation. Our selection policy for transplantation has been describedpreviously.4The age distribution of the recipients ranged from 9 days to 69 years (Figure 1). The twenty-five patients who were in their seventh decadeof life included 24 men and 1 woman (mean age 63 years, range 60 to 69). Before transplantation, 16 patients were in New York Heart Association class IV and 9 in class III. The etiology of their cardiac failure was coronary artery diseasein 21 (84%) patients (compared with 53% overall in our transplant recipients4) and idiopathicdilated cardiomyopathy in 4 (16%). Seven patients (29%) had undergone previous major surgery (6 had open heart surgery and 1 had repair of abdominal aneurysm). One patient had sustaineda recent pulmonary embolism. Diabetic retinopathy or nephropathy, cerebrovascular diseaseand intrinsic renal or hepatic diseasewere consideredto be contraindications to transplantation. Donors were matched according to ABO compatibility and recipient’s body size. The donors’ mean age was 30 (range 14 to 46) years. All the hearts were harvested
at the donors’ hospitals and preservedwith St. Thomas’ cardioplegic solution. Total ischemic time ranged from 73 to 245 (mean 148) minutes. Nineteen recipients underwent orthotopic cardiac transplantation performed with the conventional technique of Lower and Shumway9and 6 with a new technique, developedat our hospital, in which the systemic and pulmonary veins are anastomosedleaving the donor atria intact. All patients were managedwith an immunosuppressiveprotocol that consisted of cyclosporin and azathioprine without the routine use of oral steroids.* Cyclosporin (2 to 10 mg/ kg) and azathioprine (2 mg/kg) were given preoperatively with the anesthetic premeditation and 1 g of methylprednisolone was administered intraoperatively after releasing the aortic clamp. After transplantation, the recipients continued receiving cyclosporin administered twice daily in dosesvarying between 2 and 20 mg/kg/day and adjusted according to the trough plasma level (determined by a polyspecific radioimmunoassay) and renal function, The target levels were 400 ng/ ml during the first month and 100 to 200 rig/ml subsequently. Azathioprine was given in a dose of 2 mg/kg/ day (which was reduced if the patient’s white count decreasedbelow 3.5 log/liter). Recipients were monitored for rejection as previously describede4Acute cardiac rejection, diagnosed histologically, was usually treated with either pulse dosesof intravenous methylprednisolone (1 g daily for 3 days), antithymocyte globulin, a combination of the 2 agents or with monoclonal antibodies (depending on the severity of rejection).
20
0 0
Early results: The mean stay at the intensive care unit and the median hospital stay after cardiac transplantation were 1.7 days (range 1 to 5) and 11 days (range 10 to 90), respectively. There were 4 early deaths (within 1 month), 2 from acute rejection and 2 from multiorgan failure. The mean number of rejection episodesper patient was 2.1. Only 1 patient experienced a seriousinfection (empyema of right chest after a preoperativepulmonary embolism) and recoveredfollowing 200 T
90
No at Risk:
RESULTS
25
20
180 Time
270 360 450 after transplantation
19
PtGURE 2. Actuarial survival in the seventh decade of life.
540 (Days)
630
720 6
15
of cardiac transplant
recipients
100
80
Before TX a After TX
I
Age
IGURE 1. Age distribution lant recipients at Harefield
treatment with antibiotics and decortication. Three patients had reversible impairment of renal function, which was successfullytreated by temporarily substituting steroids for cyclosporin. Two patients developed gout and 1 foot drop which improved with intensive physiotherapy. None of the recipients suffered convulsions, transient ischemic attacks or cerebrovascular accidents. None had significant psychological problems. “Late” results: There were no late deaths during a follow-up period extending from 5 to 59 months (mean 22). Six patients required antihypertensive treatment. The l-year actuarial survival was 84% (Figure 2). The 21 patients currently alive are all in New York Heart Association class I. Quality of life, assessedby the Nottingham Health Profile, 10 showed reduction in scores for all dimensions corresponding to a reduction in symp-
(years)
of 500 con Hospital.
ive cardiac brans-
dimensions in part 1 of the IGURE 3. Mean scores for the Nottingham Health Profile before transplantation (lx) and 6 months after it.
THE AMERICAN JOURNAL OF CARDIOLOGY JANUARY 1. 1989
CARDIAC
TRANSPLANTATION
IN SEVENTH
DECADE
25
0 0 0 0
200
FIGURE 4. Maximal workload, oxygen uptake, heart rate and ventilation achieved during symptom-limited graded exercise on a cycle ergometer.
T
B
175~-
0 2 rP r
150~-
:: 2
0 0 0 0 0 0 0
125~loo-
0
0
0 0
0 0
0 0
0 0
0
75 i
toms and perceived health problems (Figure 3). The results of the most recent cardiopulmonary exercise tests (performed at a mean of 6 months after transplantation) are shown in Figure 4. Due to cardiac denervation, peak heart rates based on the age of the patient were lower than predicted. Peak oxygen uptake was also lower than predicted,l1 but sufficient to allow a good level of rehabilitation in all patients. Long-term survivors underwent coronary angiography at annual intervals after transplantation. Only 1 of 19 patients has been found to have angiographically evident coronary artery diseasein the transplanted heart (which was of moderate severity and was demonstrated 1 year after operation). This patient is currently asymptomatic and with no evidence of diseaseprogression or left ventricular function deterioration. He is currently under observation and has not been considered for retransplantation.
The length of hospitalization and cost of cardiac transplantation for our patients was similar to those for younger patients at our hospital. The quality of life and degreeof rehabilitation achievedby thesepatients after transplantation was good. The incidence of coronary artery disease (5.3% at 1 year) is similar to our overall experience in cardiac transplant recipients treated with cyclosporin and azathioprine without the routine use of corticosteroids (3% at 1 year).4 Successfulcardiac transplantation in this age group greatly increasesthe number of potential cardiac transplantation candidates becauseof the high incidence of coronary artery diseasein Western societies.Already, recipients in the sixth decadeof life comprisethe second largest group in our program (Figure 1). The scarce supply of donor organs limits the activity of cardiac transplant programs.14J5It appearsthat this will be the main factor among the restrictions for cardiac transplantation in the older patients.6,7There are many factors influencing the supply of donor organs that are beyond the control of individual cardiac transplantation units.14 However, measuressuch as extending age range for potential cardiac donors and using hearts from heart and lung transplant recipients4may help to alleviate this problem.
DISCUSSION Our results demonstrate that cardiac transplantation can be performed in the seventh decadeof life with survival rates as well as frequency of rejection and complication rates that are similar to those seen in younger age groups. We believe the low incidence of infection in our serieswas probably due to the avoidance of routine oral steroids combined with the use of prophylactic antibiotics and acyclovir. 12J3Only 1 serious infection oc- REFERENCES 1. Griffith BP, Hardesty RL, Trento A, Kormos RL, Bahnson HT. Cardiac curred in this age group (incidence 4%) compared with transplantation-emerging from an experiment to service. Ann Surg 1986; 5.2% in a consecutive seriesof 96 cardiac transplant re- 204:308-314. cipients at our hospital.13The incidence of rejection (2.1 2. Levett JM, Karp RB. Heart transplantation. Surg Clin North Am 1985; episodesper patient) is similar to our general experience 65:613-635. 3. Kahan BD. Immunosuppressive therapy with cyclosporin for cardiac trans(1.8 episodesin the first 3 months after operation.)8 The plantation. Circulation 1987:75:40-56. incidence of other complications that might be expected 4. Banner NR, Fitzgerald M, Khaghani A, Aravot D, Reid C, Mitchell AG, Radley Smith R, Yacoub MH. Cardiac transplantationat Harefield Hospital. In: in elderly patients such as renal failure, hypertension Terasaki P, ed. Clinical Transplants 1987. Los Angeles: UCLA Tissue Typing Laboratory, 1987:17-26. and cerebral events was not increased in this series.
92
THE AMERICAN JOURNAL OF CARDIOLOGY
VOLUME 63
5. Kaye MP. The Registry of the International Society for Heart Transplantation: fourth official report--1987. In: Terasaki P, ed. Clinical Transplants 1987. Las Angeles: ULCA Tissue Typing Laboratory, 1987:1-6. 6. Copeland JG, Emery RW, Levinson MM, Icenogle TB, Carrier M, Olt RA, Copeland JA, McAleer-Rhenman MJ, Nicholson SM. Selection of patients for cardiac transplantation. Circulation 1987;75;2-9. 7. Szentpelery S, Thames M, Hanrahan J, Morris J, Lower RR. Cardiac transplantation in the sixth decade of life. Transplant Pmc /987;19:2492-2494. 8. Yacoub M, Alivizatos P, Khaghani A, Mitchell A. The use of cyclosporin, azathioprine and antithymocyte globulin with or without low dose steroids for immunosuppression of cardiac transplantation. Transplant Proc 1985;17:221~ 222. 9. Lower RR, Shumway NE. Studies on orthotopic homotransplantation of the canine heart. Surg Forum 1960;11:18-19.
10. Hunt SM, McEwen .I. The development of a subjective health indicator Health IIlness 19X%2:231 -245. 11. Jones NL, Campbell EJM. Clinical Exercise Testing. Philadelphia: WB Saunders, 1982,249. 12. Ashraf MH, Campalani GC, Qureshi SA, Fraud DJ, Yacoub MH. Acyclovir in treatment of cytomegalovirus pneumonia after cardiac transplantation. Lam% 1982:1:173-174. 13. Khaghani A, Martin M, Fitzgerald M, Skacel M, Aravot D, Yacoub MH. Cefotaxime and tlucloxacillin as antibiotic prophylaxis in cardiac transplantation. Drugs 1988;35(suppl2):124-126. 14. Robertson JA. Supply and distribution of hearts for transplantation: legal, ethical and policy issues. Circulation 1987;7.5:77-87. 15. Casscells W. Heart transplantation-recent policy developments. N Engl J Med 1986:3lS:1365-1368.
Sociof
THE AMERICAN JOURNAL OF CARDIOLOGY JANUARY 1, 1989