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Cardiac retransplantation: A viable option?☆

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Cardiac Retransplantation: A Viable Option? Shreekanth V. Karwande, MD, R. Douglas Ensley, MD, Dale G. Renlund, MD, William A. Gay, Jr, MD, Wayne E. Richenbacher, MD, Donald B. Doty, MD, M. Elizabeth Hammond, MD, John D. Marks, PE, and The Registry of the International Society for Heart and Lung Transplantation Division of Cardiothoracic Surgery, University of Utah School of Medicine, and Utah Transplant Affiliated Hospitals Cardiac Transplant Program, Salt Lake City, Utah To evaluate cardiac retransplantation as an appropriate utilization of scarce donor organs we analyzed data from the registry of the International Society for Heart and Lung Transplantation (ISHLT) (n = 449) and the Utah Cardiac Transplant Program (n = 20). Actuarial survival among retransplants was lower than in patients who received only one transplant in both the ISHLT registry patients (1 year survival, 48% versus 78%; p = 0.001) and the Utah series (1 year survival, 74% versus 88%; p = 0.06). Uncontrolled rejection, short interval (<6 months) between transplantations, and the need for mechanical circulatory support were identified as risk factors for retransplantation. The incidence of rejection and infec- tion was similar in first and second transplant recipients. ince the first report of cardiac retransplantation in S 1977, more than 400 such procedures have been reported to the registry of the International Society for Heart and Lung Transplantation (ISHLT) [l, 21. The three principal causes of allograft failure leading to retransplan- tation are accelerated allograft coronary artery disease (ACAD), rejection, and nonspecific graft failure. In view of the acute shortage of donor organs we decided to examine cardiac retransplantation by using data from two sources. All recipients of a second heart transplant reported to the ISHLT registry were compared with a matched group of first heart transplant recipients. Data for retransplanta- tion recipients in the Utah Cardiac Transplant Program were collected to compare and contrast with the ISHLT data and to examine variables not covered by the registry data. Material and Methods Second transplant recipients had a higher level of sensi- tization, a greater incidence of donor-specific positive crossmatches, and an increased early mortality. Repeti- tion in the second donor of mismatched HLA antigens present in the first donor did not adversely affect sur- vival. If patients who underwent retransplantation within 6 months of their initial transplantation, those receiving transplants for uncontrolled rejection, and those requiring mechanical assistance were eliminated from the study, the short-term and long-term survival after cardiac retransplantation does not differ from that in patients having a single transplant. (Ann Thorac Surg 1992;54:840-5) were matched for transplant center, year of transplanta- tion, age, and sex. Outcome variables examined included survival and cause of death. Potentially predictive vari- ables examined were age, sex, cause of allograft failure, interval between first and second transplantation, immu- nosuppressive regimen, and experience of the transplant center. Utah Cardiac Data Between March 1985 and December 1991 420 cardiac transplantations were performed, 20 of which were sec- ond transplant procedures. Third transplant procedures required in 2 patients were not included in the analysis. All of the variables mentioned above, with the addition of HLA typing, donor-specific crossmatch, percent panel reactive antibody (PRA), cholesterol, rejection episodes, infection episodes, surgical mortality, and development of malignancy were examined. Induction immunosup- - pression was used in all patients after primary transplan- tation. A prospective PRA screen was performed in all patients. A PRA in excess of 10% required a negative tion. In addition to routine light microscopy, immunoflu- ISHLT Registry Data Between November 1968 and October 1991 the ISHLT retransplantation worldwide. Data were also analyzed for registry received data for 449 recipients who undenvent donor-specific lymphocyte crossmatch before transplants- an number Of Primary who OreScence staining of endomyocardial biopsy specimens was performed in the majority of patients (n = 268). Rejection was characterized as cellular, vascular (humor- al), or mixed according to previously described criteria [3, Presented at the Twenty-eighth Annual Meeting of The Society of Thoracic Surgeons, Orlando, FL, Feb SS, 1992. Address reprint requests to Dr Karwande, Division of Cardiothoracic Surcrerv, Universitv of Utah Medical Center, SO North Medical Dr, Salt 41. biopsies and coronary angiograms were L a c City, UT 84132. performed as per protocol. 0 1992 by The Society of Thoracic Surgeons 0003-4975/92/$5.00
Transcript
Page 1: Cardiac retransplantation: A viable option?☆

Cardiac Retransplantation: A Viable Option? Shreekanth V. Karwande, MD, R. Douglas Ensley, MD, Dale G. Renlund, MD, William A. Gay, Jr, MD, Wayne E. Richenbacher, MD, Donald B. Doty, MD, M. Elizabeth Hammond, MD, John D. Marks, PE, and The Registry of the International Society for Heart and Lung Transplantation Division of Cardiothoracic Surgery, University of Utah School of Medicine, and Utah Transplant Affiliated Hospitals Cardiac Transplant Program, Salt Lake City, Utah

To evaluate cardiac retransplantation as an appropriate utilization of scarce donor organs we analyzed data from the registry of the International Society for Heart and Lung Transplantation (ISHLT) (n = 449) and the Utah Cardiac Transplant Program (n = 20). Actuarial survival among retransplants was lower than in patients who received only one transplant in both the ISHLT registry patients (1 year survival, 48% versus 78%; p = 0.001) and the Utah series (1 year survival, 74% versus 88%; p = 0.06). Uncontrolled rejection, short interval (<6 months) between transplantations, and the need for mechanical circulatory support were identified as risk factors for retransplantation. The incidence of rejection and infec- tion was similar in first and second transplant recipients.

ince the first report of cardiac retransplantation in S 1977, more than 400 such procedures have been reported to the registry of the International Society for Heart and Lung Transplantation (ISHLT) [l, 21. The three principal causes of allograft failure leading to retransplan- tation are accelerated allograft coronary artery disease (ACAD), rejection, and nonspecific graft failure. In view of the acute shortage of donor organs we decided to examine cardiac retransplantation by using data from two sources.

All recipients of a second heart transplant reported to the ISHLT registry were compared with a matched group of first heart transplant recipients. Data for retransplanta- tion recipients in the Utah Cardiac Transplant Program were collected to compare and contrast with the ISHLT data and to examine variables not covered by the registry data.

Material and Methods

Second transplant recipients had a higher level of sensi- tization, a greater incidence of donor-specific positive crossmatches, and an increased early mortality. Repeti- tion in the second donor of mismatched HLA antigens present in the first donor did not adversely affect sur- vival. If patients who underwent retransplantation within 6 months of their initial transplantation, those receiving transplants for uncontrolled rejection, and those requiring mechanical assistance were eliminated from the study, the short-term and long-term survival after cardiac retransplantation does not differ from that in patients having a single transplant.

(Ann Thorac Surg 1992;54:840-5)

were matched for transplant center, year of transplanta- tion, age, and sex. Outcome variables examined included survival and cause of death. Potentially predictive vari- ables examined were age, sex, cause of allograft failure, interval between first and second transplantation, immu- nosuppressive regimen, and experience of the transplant center.

Utah Cardiac Data Between March 1985 and December 1991 420 cardiac transplantations were performed, 20 of which were sec- ond transplant procedures. Third transplant procedures required in 2 patients were not included in the analysis. All of the variables mentioned above, with the addition of HLA typing, donor-specific crossmatch, percent panel reactive antibody (PRA), cholesterol, rejection episodes, infection episodes, surgical mortality, and development of malignancy were examined. Induction immunosup- - pression was used in all patients after primary transplan- tation. A prospective PRA screen was performed in all patients. A PRA in excess of 10% required a negative

tion. In addition to routine light microscopy, immunoflu-

ISHLT Registry Data Between November 1968 and October 1991 the ISHLT

retransplantation worldwide. Data were also analyzed for registry received data for 449 recipients who undenvent donor-specific lymphocyte crossmatch before transplants-

an number Of Primary who OreScence staining of endomyocardial biopsy specimens was performed in the majority of patients (n = 268). Rejection was characterized as cellular, vascular (humor- al), or mixed according to previously described criteria [3,

Presented at the Twenty-eighth Annual Meeting of The Society of Thoracic Surgeons, Orlando, FL, Feb S S , 1992.

Address reprint requests to Dr Karwande, Division of Cardiothoracic Surcrerv, Universitv of Utah Medical Center, SO North Medical Dr, Salt 41. biopsies and coronary angiograms were L a c City, UT 84132. performed as per protocol.

0 1992 by The Society of Thoracic Surgeons 0003-4975/92/$5.00

Page 2: Cardiac retransplantation: A viable option?☆

Ann Thorac Surg 1992;54:84&5

KARWANDE ET AL 841 CARDIAC RETUANSPLANTATION

- First Transplants ---- Second Transplants

I I I I I I I 1 I i 0 6 12 18 24 30 36 42 48 54 60

Months Post Transplant

Fig 1 . (ISHLT registry data.) Actuarial analysis of survival of second transplant recipients and a matched group of first transplant recipi- ents demonstrating a decreased survival (78% versus 48%) in the re- transplantation group.

Statistics Univariate analysis of the relationship between risk fac- tors and survival was performed by Tarone-Ware analysis of the actuarial survival curves. Multivariate analysis of actuarial survival was performed using a logistic stepwise regression model. Differences between groups were ana- lyzed using 2 tests or Fisher's exact test for discrete variables and t tests for continuous variables. Values are reported as mean * standard error of the mean. A p value of less than 0.05 was considered statistically significant.

Results ISHLT Registry Data Accelerated allograft coronary artery disease was the cause of graft failure in 63% of recipients. Rejection and nonspecific graft failure contributed 18% and 19%, respec- tively.

The 1-year actuarial survival for second transplants was significantly lower: 48% compared with 78% for first transplants ( p < 0.001). This was principally due to a high early mortality of 15% in retransplants (Fig 1). Beyond 6 months patients in both groups did not exhibit significant differences in long-term survival (Fig 2).

2ol " - 7 1 I I I I I I I I I

0 6 12 18 24 30 36 42 48 54 60

Months Post Transplant

Fig 2. (ISHLT registry data.) Actuarial analysis of survival of pa- tients surviving greater than 6 months after either repeat or primary cardiac transplantation, demonstrating no significant difference in the long-term survival between the two groups.

' O O L 80

201 01 I I I I I I I I I 1

0 6 12 18 24 30 36 42 48 54 60

Months Post Transplant

Fig 3. (ISHLT registry data.) Actuarial analysis of survival of pa- tients with intervals between transplantations of greater than and less than 6 months demonstrating a significant difference (greater 61 % 1-year survival in patients with a shorter interval).

Recipient sex and age did not affect survival after repeat transplantation. Survival was greater in patients under- going retransplantation after 1985 (1 year survival, 52%) compared with those undergoing transplantation before 1985. In terms of immunosuppressive regimens, patients who were treated with triple-therapy regimens (azathio- prine, cyclosporine, and steroids) after retransplantation fared better than those on other protocols.

The interval between transplantations was a significant predictor of survival. Patients with an interval of greater than 6 months between the first and second transplanta- tion had significantly greater survival than those under- going retransplantation within 6 months (1 year survival, 61% versus 36%; p < 0.001) (Fig 3). Patients having retransplantation for ACAD had significantly longer in- tervals between transplants compared with patients re- ceiving transplants for rejection. Mechanical assistance preoperatively was required more often in patients under- going retransplantation for rejection or nonspecific graft failure when compared with patients having transplanta- tion for ACAD (80% and 86% versus 36%; p < 0.005). Patients requiring mechanical support and those having retransplantation for intractable rejection both had lower survival rates (Fig 4). Experience of the transplant center did not affect survival in repeat transplant recipients. One-year survival was 40% for centers having performed less than 30 transplantations at the time of the index repeat transplantation as compared with 50% for centers with greater than 30 transplantations performed ( p = not significant).

Multivariate stepwise logistic regression analysis iden- tified interval between transplantations, cause of allograft failure, and year of transplantation as the most important predictive variables. An "ideal candidate" was defined as a retransplant patient with allograft failure due to an interval between transplantations of greater than 6 months, with a date of second transplantation after 1985, and without preoperative mechanical support. Patients meeting these criteria had a 1-year survival of 64%, still lower than the survival rate of 79% for first transplant recipients.

Page 3: Cardiac retransplantation: A viable option?☆

842 KARWANDE ET AL CARDIAC RETRANSPLANTATION

Ann Thorac Surg 1992;54:84&5

...... R e i e c t i i

0 ) I I I I I I I I I I 0 6 12 18 24 30 36 42 48 54 60

Months Post Transplant

Fig 4 . Actuarial suwival of patients reported to the ISHLT registry after repeat transplantation for either accelerated allograft coronary artery disease (ACAD), rejection, or nonspecific graft failure. Rejec- tion and nonspecific graft failure patients had a significantly decreased survival.

Utah Cardiac Data Characteristics of patients undergoing repeat transplanta- tion with the Utah group are similar to the ISHLT group with respect to age and sex. Accelerated allograft coronary artery disease was the cause of graft failure in 50% of the patients. Rejection and nonspecific graft failure contrib- uted 40% and lo%, respectively (Table 1). Compared with the ISHLT data, a greater proportion of patients in the Utah group underwent retransplantation for acute rejec- tion as the cause of allograft failure (40% versus 18%; p = 0.03). Despite the greater proportion of patients having retransplantation for acute rejection, the Utah series had a higher 1-year survival compared with the ISHLT group (1-year survival, 74% versus 48%) (Fig 5). In the Utah series the initial hospital mortality (30 days) was 15% in the retransplant group compared with 2.5% in the pri-

Table 1. Characteristics of Patients Undergoing Retransplantation in the ISHLT Registry and Utah Cardiac Transplant Program

Variable Registsy Cardiac ISHLT Utah

First transplant Second transplant

No. of patients Age (Y)

Cause of allograft failure ACAD Rejection Nonspecific

Male Female

Mechanical assistancea First transplant Second transplant

Sex

421 449

41.5 ? 0.7

63 % 18% 19%

80% 20 %

7% 48%

420 20

48.8

50% 40% 10%

90% 10%

10% 20%

a Intraaortic balloon pump or ventricular assist device. ACAD = accelerated allograft coronary artery disease; national Society for Heart and Lung Transplantation.

ISHLT = Inter-

1

a 401 20 - First Transplants ---- Second Transplants

0 ; I I I I I I I I I 1 o 6 12 i a 24 30 36 42 48 54 60

Months Post Transplant

Fig 5. Actuarial analysis of survival in patients with second trans- plants reported in the Utah Cardiac series. Survival after repeat trans- plantation was greater in the Utah series thun that observed in the registry patients.

mary transplant group ( p = 0.43). No difference in long- term survival was observed between patients surviving greater than 6 months after either primary or repeat transplantation (Table 2).

Patients undergoing retransplantation within 6 months of the primary transplant showed a trend toward de- creased survival (1-year survival, 56% versus 91%; p = 0.24). All patients receiving transplants within 6 months of the primary transplantation had rejection or a nonspe- cific cause for allograft failure. Patients undergoing re- transplantation for ACAD had significantly longer inter- vals between transplantations (26.4 months versus 4.2 months; p < 0.001).

The incidence of surgical complications was markedly increased in the retransplantation group. The operating room mortality was 10% compared with 1.5% in the primary transplant recipients ( p = 0.05). The incidence of mediastinitis was also increased (10% versus 2.5%; p = 0.11). No difference was noted between first and second transplant recipients for the number of days to the first treated rejection episode (63 days versus 46 days; p = not significant) or number of rejection episodes in the first 4 months (1.3 versus 1.6; p = not significant). There was also no difference in the number of major infections during the first 12 months (0.56 versus 0.78; p = not significant).

Table 2 . Survival Characteristics of Patients in the Utah Cardiac Program Undergoing Repeat Transplantation

Variable One-Year Survival p Value

Patients surviving >6 months First transplants Repeat transplants

Transplant interval >6 months <6 months

For ACAD For Rejection

Repeat transplantation

NS 98% 92%

91% 56%

90% 56%

NS

NS

ACAD = accelerated allograft coronary artery disease.

Page 4: Cardiac retransplantation: A viable option?☆

Ann Thorac Surg 1992;54:84&5

KARWANDE ET AL 843 CARDIAC RETRANSPLANTATION

Table 3 . HLA Sensitization in Primary and Repeat Transplants in the Utah Cardiac Transplant Program

Variable Transplant Transplant First Second

PRA >lo% 2.7% Positive crossmatch 2.8%

20% 15%

PRA = Panel reactive antibody

HLA matching data with regard to the second donor were available in 15 of 20 patients. In 13 patients (87%) there was repetition in the second donor heart of mis- matched HLA antigens in the first allograft. The 1-year survival in this group with repeated mismatched antigens was 77%. Patients undergoing retransplantation exhibited a greater degree of sensitization as evidenced by a higher mean PRA and a 15% incidence of positive retrospective donor-specific lymphocyte crossmatch compared with 2.8% in primary transplant recipients ( p = 0.02) (Table 3). Two of 3 patients with a positive crossmatch died.

Based on immunofluorescence of endomyocardial bi- opsy specimens all transplant patients were classified as manifesting predominantly vascular, mixed, or cellular rejection. Patients classified as having a vascular pattern of rejection had a distinctly poorer survival. The risk of development of allograft coronary disease was higher in patients with vascular or mixed rejection pattern. Angio- graphically determined incidence of coronary artery dis- ease was 15% (63/420). Of these 63 patients, 51 patients (80%) had either a vascular or mixed biopsy pattern. Immunofluorescence biopsy data were available for both the first and second transplants on 11 recipients. All except 1 patient repeated their biopsy pattern in the second transplant.

In comparing patients requiring retransplantation for ACAD with other patients requiring retransplantation no differences were found in serum cholesterol levels or age of donor hearts. Serum cholesterol levels were signifi- cantly ( p < 0.02) higher in patients receiving corticoster- oids. Patients who were listed as UNOS status 1 before retransplantation had a lower survival (1-year survival, 60% versus 90%; p = not significant). The requirement of mechanical assistance (intraaortic balloon pump or ven- tricular assist device) was doubled in the retransplant group in comparison with primary transplants (20% ver- sus 10%; p = not significant) (see Table 1).

Although the incidence of rejection and infection did not differ between the first and second transplant recipi- ents, the incidence of malignancy was increased after repeat transplantation (5% versus 2.3%; p = 0.39).

Comment Only a few centers have reported their experience with retransplantation [5-71. To review a broad spectrum of patients we decided to analyze the ISHLT data and our own. Several of the questions that clinicians are faced with when making decisions regarding the candidacy of a patient for retransplantation were considered.

Survival In the ISHLT registry data two closely matched patient groups were compared. The survival in the retransplant group was markedly decreased (1-year survival, 48% versus 79%; p < 0.001) compared with that in primary transplant recipients, with the majority of the increased mortality occurring in the early posttransplantation pe- riod. Although a trend toward decreased survival in retransplantation patients was also observed in the Utah group (1-year survival, 74% versus 88%; p = 0.06), this difference was less marked than in the ISHLT data. Most individual centers [5, 71 and ISHLT have reported mark- edly decreased survival in retransplantation patients. In the Columbia series [6], survival was no different. Here we report a trend toward slightly decreased survival that did not achieve statistical significance. Recipients of sec- ond transplants in the Utah Cardiac series had greater survival than those in the ISHLT registry despite a higher percentage of patients undergoing retransplantation for intractable rejection in the Utah Cardiac series (see Fig 5). In both groups patients surviving beyond 6 months after repeat transplantation had a long-term survival not sig- nificantly different than that in patients surviving 6 months after primary transplantation. The ISHLT registry patients having retransplantation due to rejection as the cause of allograft failure had a decreased survival (1-year survival, 33%) when compared with those receiving trans- plants for ACAD (see Table 2). A similar trend was also seen in the Utah series (1-year survival, 56% versus 90%; p = 0.25) but did not achieve statistical significance because of the small numbers. The shorter interval be- tween transplantations and greater hernodynamic insta- bility observed may be the main factors contributing to the decreased survival seen in patients undergoing transplan- tation for rejection [5, 81.

Mechanical Assistance In both the ISHLT registry (48% versus 7%) and Utah Cardiac (20% versus 10%) series retransplant patients were more likely to require mechanical assistance. In both series patients having retransplantation for nonspecific graft failure or rejection were more likely to require mechanical support than those having retransplantation for ACAD.

Transplantation Interval In the ISHLT registry there was a marked impact on survival between patients receiving transplants within 6 months of the first transplantation as compared with those receiving transplants with an interval of greater than 6 months (1-year survival, 36% versus 61%; p < 0.001) (see Fig 3). A similar trend was observed in the Utah Cardiac series, although the difference (1-year sur- vival, 56% versus 91%) did not approach statistical signif- icance ( p = 0.24) (see Table 2). In the Utah series all patients undergoing transplantation within 6 months of the primary transplantation had either rejection or a nonspecific cause for allograft failure. Several factors may be responsible for the improved survival in recipients with a longer interval between first and second transplan-

Page 5: Cardiac retransplantation: A viable option?☆

&14 KARWANDEETAL CARDIAC RETRANSPLANTATION

AM Thorac Surg 1992;54:84&5

tations. Because immunosuppressive requirements are higher initially, those with a longer interval between transplantations are likely to be receiving lower doses of immunosuppressive agents and corticosteroids at the time of repeat transplantation. Additionally they have had time to recover from the first transplant operation.

In the Utah group, trends toward decreased survival were observed in retransplant patients with shorter inter- vals between transplantations and in those with rejection as the cause of allograft failure, but these differences did not achieve statistical significance. The failure of these differences to achieve statistical significance may in part be due to the smaller number of patients in the Utah series.

Infection, Rejection, and Malignancy Prolonged high-level immunosuppression during retrans- plantation may predispose the recipient toward infection or malignancy. Analysis of the data from the Utah Cardiac series confirms the observation made by others [5, 61 that rejection and infection episodes do not occur more fre- quently in recipients of second allografts. In the Utah Cardiac series patients undergoing repeat transplantation had an incidence of malignancy of 5% compared with 2.3% in primary transplant recipients ( p = 0.39). Rejection pattern as defined by immunofluorescence microscopy (vascular, mixed, or cellular) was repeated from the first to the second transplantation in all but 1 patient. Patients with a vascular rejection pattern tend to have lower survival. An increased incidence of allograft coronary artery disease is seen in patients who manifest vascular and mixed rejection patterns in biopsy specimens [9]. It is conceivable that in the future this might become one of the factors to be considered when deciding on the candi- dacy of a retransplant patient.

Surgical Complications Retransplant recipients both in the ISHLT registry and the Utah cardiac series exhibited an increased mortality in the early posttransplantation period. In the Utah series these patients had a higher incidence of mediastinitis, probably related to their hemodynamically unstable status and greater level of immunosuppression.

Antigenic Status Recipients undergoing repeat transplantation had a much higher incidence of sensitization to the standard panel of antigens than candidates for primary transplantation (see Table 3). Blood transfusions and exposure to donor- specific antigens of the first allograft may contribute to increased sensitization. In the Utah series, 13 retrans- planted patients had repetition in the second allograft of HLA antigens present in the first allograft. This did not affect survival (1-year survival, 77%), as has been reported in renal transplantation [lo, 111. The clinical implication of this observation is that preoperative donor HLA typing and crossmatching is probably indicated only in recipients who are highly sensitized as shown by a high panel reactive antibody titer.

Conclusions Survival is decreased in patients undergoing repeat trans- plantation compared with patients undergoing primary transplantation. Patients having retransplantation for re- jection and within 6 months of the first transplantation tend to have lower survival rates. Operative mortality (24 hours) and hospital mortality (30 days) are markedly increased after repeat transplantation. The requirement of preoperative mechanical assistance is high in second transplant recipients, especially those having retransplan- tation for rejection and nonspecific graft failure. Most patients undergoing retransplantation for rejection and nonspecific graft failure require retransplantation within 6 months of the primary transplantation. Most patients having retransplantation for ACAD do not require re- transplantation until 6 months or longer after the primary transplantation. Infection and rejection do not occur more frequently after repeat transplantation. If the early mor- tality can be overcome, the long-term survival is excellent. Immunofluorescence of myocardial biopsy specimens could be helpful as a predictor of accelerated graft athero- sclerosis. In deciding the candidacy of a recipient for repeat transplantation the above factors should be consid- ered.

References 1.

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Kriett JM, Kaye MP. The Registry of the International Society for Heart and Lung Transplantation: eighth official report- 1991. J Heart Lung Transplant 1991;10:491-8. Kriett JM, Kaye MP. The Registry of the International Society of Heart Transplantation: seventh official report-1990. J Heart Transplant 1990;9:323-30. Hammond EM, Ensley RD, Yowell RL, et al. Vascular rejec- tion of human cardiac allografts and the role of humoral immunity in chronic allograft rejection. Transplant Proc 1991;23:26-30. Hammond ME, Wittwer CT, Greenwood J, et al. Relation- ship of OKT3 sensitization and vascular rejection in cardiac transplant patients receiving OKT3 rejection prophylaxis. Transplantation 1990;50:776-82. Dein JR, Oyer PE, Stinson EB, Starnes VA, Shumway NE. Cardiac retransplantation in the cyclosporine era. Ann Tho- rac Surg 1989;48:350-5. Michler RE, McLaughlin MJ, Barr ML, et al. Clinical experi- ence with cardiac retransplantation. J Thorac Cardiovas Surg (in press). Cabrol C, Gandjbakhch I, Pavie A, et al. Is the use of artificial hearts the future solution for interim treatment of patients awaiting retransplantation? Transplant Proc 1989;21:365%9. DeBoer J, Cohen 8, Thorogood J, Zantvoort FA, DAmaro J, Persijn G. Results of acute heart retransplantation. Lancet 1991;337:1158. Hammond EM, Yowell RL, Price GL, et al. Vascular rejection and its relationship to allograft coronary artery disease. J Heart Lung Transplant 1992;11:111-9. Stratta RJ, Choong-San 0, Sollinger HW, Pirsch JD, Ka- layoglu M, Belzer FO. Kidney retransplantation in the cyclos- porine era. Transplantation 1988;45:40-5. Almond PS, Matas AJ, Gillingham K, et al. Risk factors for second renal allografts immunosuppressed with cyclospo- rine. Transplantation 1991;52:25%3.

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KARWANDE ET AL 845 CARDIAC RETRANSPLANTATION

DISCUSSION

DR ADNAN COBANOGLU (Portland, OR): I congratulate the Utah team for their outstanding results in a very difficult group of transplant patients and also for their contributions in heart transplantation over the years. We have a much more sobering experience in Oregon at the University Hospital in Portland. Since December 1985 we have performed 175 heart transplanta- tions and 9 of them were second transplantations; only 3 patients survived up to 1 year. So the 1-year survival is in the mid-30% range, and those who survived underwent transplantation early and for rejection. This is within weeks to months of the first transplantation. So these patients are extremely difficult to deal with. Your results are quite good, although not as good as the first-time transplantations.

We have found ourselves at times having to deal with your last conclusion, the philosophical dilemma, as to whether we should allocate a second or a third heart to those patients who may need them.

I have felt that the reason the 3 patients in whom we performed retransplantation survived was because they had not been on chronic immunosuppression and chronic steroid therapy in terms of many months or years. Now, we know, and the literature is replete with reports, that any major operation carries a high risk if patients have been on chronic steroid therapy, for whatever reason. I would have expected these patients to have a relatively higher risk overall of wound complications and medi- astinitis, much more than your slides showed, and that actually may be the experience in other active centers in the country.

In any case, I congratulate you for your results and let you know of this sobering note from your northern neighbor state.

DR PETER P. McKEOWN (Tampa, FL): I also compliment Dr Karwande and associates and would like to ask them if they could fill a gap in our knowledge. We also have been somewhat concerned about vascular rejection and its role for retransplanta-

tion or recurrent rejection. Have you looked at the incidence or the frequency of cytotoxic antibodies in your patient cohort, and has that seemed to be related to immunosuppression, that is, is it more frequent in patients treated with OKT3 versus the non-OKT3 induction group?

Second, I compliment you on using the immunoperoxidase. If you did have positive immunoperoxidase in a patient who was going to be a retransplantation candidate, would you again alter your immunosuppression and perhaps have a broader spectrum with MALG or RATG?

DR KARWANDE: Let me start first with Dr Cobanoglu. We were also surprised with the low level of infection in these patients. I think the possible explanation for that would be that infection is related to the level of immunosuppression at the time of retrans- plantation. On the other hand, the incidence of malignancy, which we also looked at but I did not allude to in this presenta- tion, is probably more representative of the cumulative level of immunosuppression.

In terms of the level of sensitization, we have a protocol for patients on OKT3 management in which we monitor plasma levels of OKT3 as well as CD3 lymphocytes. We are extremely aware of xenosensitization when patients have required pro- longed therapy with OKT3. In terms of immunosuppression, most of our patients had induction immunosuppression for the first transplant, and for the second transplant standard triple- therapy immunosuppression was used.

Specifically, in response to Dr McKeown’s question regarding cytotoxic antibodies, we obtain a PRA level before transplanta- tion. In the last 6 months we have started monitoring donor- specific antibodies at regular intervals. Patients undergoing re- transplantation with vascular rejection and immunofluorescent positivity will require more aggressive immunosuppression.


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