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R C Bourge

Publications and source records attributed to R C Bourge.

90 records · Page 5Linked to original sources

Cost-benefit analysis of extended antifungal prophylaxis in ventricular assist devices.

This report defines the cost and benefit of extended antifungal prophylaxis in ventricular assist device (VAD) patients (pts). Extended antifungal prophylaxis is defined as prophylaxis with fluconazole or nystatin that is given until pts are extubated and off antibiotics. These data are compared with that obtained from earlier VAD patients who only received anti-fungal drugs for documented fungal colonization or infection. Thirty-six patients had HeartMate (n = 15) or Thoratec (n = 21) VADs between 1989 and 1997. Cultures positive for fungus (n = 52 cultures) were obtained from 16 of 36 patients (44% of patients). Forty-three fungal cultures were in the preprophylaxis and nine in the postprophylaxis era. There was one death attributable to fungal sepsis in the preprophylaxis era and none in the postprophylaxis era. The total cost of antifungal drugs in the preprophylaxis era was $3,840 over 1,498 patient days (PD) (mean $2.56 per PD), versus $70,670 over 1,525 PD in the postprophylaxis era (mean $46.34 per PD). Extended antifungal prophylaxis was not cost effective in VAD patients at this institution. However, short-term perioperative antifungal prophylaxis was not addressed by this study. We are now using short-term antifungal prophylaxis with fluconazole and nystatin in VAD patients because of the potential for serious morbidity and mortality that is associated with fungal device infections. A future analysis will determine the usefulness of this change in strategy.

Antifungal Agents↗

Total lymphoid irradiation in the treatment of early or recurrent heart rejection.

UNLABELLED: Total lymphoid irradiation (TLI) has been shown experimentally to induce a state of partial tolerance when administered before organ transplantation. Anecdotal reports in clinical transplantation have suggested efficacy of TLI in the treatment of recurrent rejection after heart transplantation. To further assess the safety and efficacy of TLI, 19 patients were entered into a protocol of TLI for the treatment of recurrent or early severe rejection despite conventional therapy. Rejection rate decreased from 1.3 episodes/month before TLI to 0.53 during TLI and 0.07 after TLI (p < 0.0001). Infections increased during TLI (possibly related to recent augmented immunosuppression before TLI), but all infections were successfully treated. One death occurred after TLI from acute allograft rejection. White blood cell (WBC) and platelet counts were depressed during and after (3 months) TLI. Frequent adjustments of dosing interval and, occasionally of the dosage were required to control WBC and platelet counts. Five patients experienced transient WBC of less than 1000/ml. More rejection episodes (and thus greater overall immunosuppression) before TLI and a lower tolerated dose of azathioprine before TLI predicted (by multivariate analysis) a lower WBC during TLI. CONCLUSIONS: (1) TLI is an effective adjunct for the intermediate control of early or recurring acute allograft rejection. (2) Close surveillance of WBC and platelets with appropriate adjustment of TLI dose and interval is necessary during TLI therapy. (3) The long-term benefits, possible late deleterious effects, and potential role of TLI as induction therapy remain to be elucidated.

Adolescent↗

Methotrexate pulse therapy in the treatment of recurrent acute heart rejection.

Despite cytolytic induction therapy and triple-drug immunosuppression, acute allograft rejection continues to cause important morbidity and occasional death after heart transplantation. Between November 1, 1988, and May 1, 1990, 24 patients received methotrexate pulse therapy for recurrent or persistent acute rejection despite methylprednisolone, OKT3, or antithymocyte globulin therapy. Methotrexate was administered as a daily oral dose of 2.5 to 15 mg on 1 day/week over 3 weeks (longer in 15 patients because of either severe leukopenia with temporary interruption of therapy or recurrent rejection during methotrexate therapy) with reduction or discontinuation of azathioprine. Rejection incidence was reduced from 1.1 episodes/patient month before methotrexate therapy to 0.2 episodes/patient month after completion of therapy (p = 0.0001). Two patients died within 3 months after treatment, one of cytomegalovirus pneumonia and one of lymphoma. Mean white blood count (WBC) fell from 6900 per ml before methotrexate therapy to 3700 during the first month of methotrexate therapy (p = 0.0005). The lowest WBC typically occurred about 3 weeks after starting methotrexate therapy, and a transient WBC of less than 1000/ml developed in seven patients. By multivariable analysis, the WBC 1 month after starting methotrexate therapy was significantly related to greater bone marrow suppression (lower WBC), immediately before methotrexate therapy, greater overall immunosuppression (more rejection episodes) during the 3 months before methotrexate therapy, and a higher total dose of methotrexate. The following conclusions can be drawn: (1) Methotrexate is a useful adjunct in the treatment of recurrent or persistent rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Cyclosporine blood monitoring after heart transplantation: a prospective comparison of monoclonal and polyclonal radioimmunoassays.

Management of heart transplant patients who are being given cyclosporine is complicated by the variety of methods available for measuring cyclosporine levels and the current trend toward exclusive use of monoclonal assays. To facilitate clinical decisions regarding cyclosporine levels when converting from a polyclonal system to monoclonal system, 79 heart transplant patients underwent a prospective study to compare the polyclonal radioimmunoassay with the monoclonal-specific parent compound and nonspecific radioimmunoassays. Multivariable regression analyses were performed to generate best-fit equations for conversion of one assay to another. The closest correlation was noted in converting the measurement of cyclosporine parent compound with metabolites by the polyclonal method to the monoclonal method (nonspecific), R2 = 0.93. Considerable variability existed in the relationship between polyclonal and monoclonal-specific levels (R2 = 0.66) and between monoclonal-nonspecific and monoclonal-specific levels (R2 = 0.66), and both relationships were affected by hepatic function. Inferences: (1) The conversion of numeric cyclosporine levels from parent compound to parent plus metabolites is not completely predictable and must be empirically determined with the generation of appropriate regression equations. (2) Caution is advisable when a transplant team adopts a new cyclosporine assay for clinical use; formal study between existing assay methods and any newly adopted assay is warranted to prevent inadvertent underdosing or overdosing with cyclosporine.

Cyclosporine↗

Renal, hemodynamic, and electrocardiographic effects of low versus high osmolality contrast agents on the transplanted heart.

The effects of low and high osmolality ionic contrast agents on the transplanted heart were studied in 75 consecutive patients. Renal function remained unchanged 24 hours after coronary angiography in both groups. Hemodynamic changes were transient and more pronounced after administration of the high osmolality agent; ECG changes and cineangiography quality were similar after both agents. The manyfold increase in cost of the low osmolality contrast agents may not be justified for use in stable patients after heart transplantation.

Contrast Media↗

Pulmonary vascular resistance and the risk of heart transplantation.

Elevated pulmonary vascular resistance was an incremental risk factor for premature death after heart transplantation (p = 0.0002). Its effect was continuously variable and not dichotomous (yes or no). The rate of rise in risk of death corresponded quite evenly to the progressive increase in pulmonary vascular resistance from low to high values, rather than abruptly increasing at a certain point. This effect was incremental to the risk imposed by congenital heart disease (in contrast to idiopathic or ischemic cardiomyopathy). Expression of the pulmonary vascular resistance in units times square meters provides more accurate predictions than expression in Wood units (p for difference = 0.03).

Heart Transplantation↗

Risk factors for late recurrent rejection after heart transplantation: a multiinstitutional, multivariable analysis. Cardiac Transplant Research Database Group.

BACKGROUND: Previous studies of allograft rejection have focused on early episodes and risk factors from pretransplant variables. METHODS: This multiinstitutional study compared early (< 1 year) and late (> 1 year) rejection episodes and risk factors for recurrent rejection from variables both before and after transplantation among 1251 patients who underwent primary heart transplantation and available follow-up of greater than 1 year. RESULTS: There were a total of 1882 rejection episodes over a mean follow-up of 26 +/- 0.3 months. The hazard function (instantaneous risk per patient per month) peaked at 1 month followed by a low constant risk of rejection after 12 months. By multivariable analysis, the most dominant risk factors for recurrent rejection during the first posttransplantation year were a shorter time interval since transplantation and a shorter time since a previous rejection episode. Other factors included young age, female gender, female donor, positive cytomegalovirus serology, prior infections, and OKT3 induction. In contrast, after the first year, the dominant risk factors for rejection were a greater number of rejections during the first year and the presence of prior cytomegalovirus infections. CONCLUSIONS: These data show a striking time dependency for rejection episodes among heart transplant recipients. Factors that increase risk for rejection in the first year differ from risk factors for rejection in subsequent years. These data suggest that it may be possible to tailor rejection surveillance protocols and immunosuppression intensity, according to specific patient and time-related risk factors.

Adolescent↗

Predictors of quality of life in patients with advanced heart failure awaiting transplantation.

BACKGROUND: Quality of life is an important outcome to measure in patients with end-stage heart disease who are awaiting heart transplantation. The purposes of this study were threefold: (1) to assess life satisfaction in multiple areas, (2) to examine correlations between life satisfaction and demographic, physiologic, and psychosocial variables, and (3) to identify predictors of quality of life in patients with advanced heart failure who were awaiting heart transplantation. METHODS: Data were collected from a convenience sample of 359 adult heart transplant candidates from a midwestern and a southern medical center. Eight instruments were used to gather data from patients. All tools had adequate psychometric support. Data were analyzed by using descriptive statistics, Pearson correlations, and stepwise multiple regression analysis. RESULTS: Results showed that patients were most satisfied with significant others (e.g., emotional support from others, children, and family's health) and least satisfied with their health and functioning (e.g., current health status, ability to travel, and energy for daily activities). Significant correlations were found between total life satisfaction and age, New York Heart Association Functional classification, total number of daily medications, functional disability, symptom distress, stress, coping, helpfulness of heart transplant team interventions, health perception, expectation of transplant success, and overall quality of life. CONCLUSIONS: Eleven of 19 variables were significant predictors of higher quality of life in patients with advanced heart failure awaiting heart transplantation and accounted for 49% of explained variance: less symptom distress, better health perception, greater helpfulness of heart transplant team interventions, less stress, better coping ability, less functional disability, less use of fatalistic coping, older age, greater effectiveness of optimistic coping, being unemployed, and the expectation of transplant success.

Activities of Daily Living↗

Influence of HLA mismatch on rejection after heart transplantation: a multiinstitutional study. The Cardiac Transplant Research Database Group.

HLA mismatch has been shown to influence survival after heart transplantation. No large multicenter study has examined the effect of HLA mismatch on cardiac allograft rejection. HLA mismatch and other potential risk factors for rejection were analyzed in data from 27 institutions (1719 patients) participating in the Cardiac Transplant Research Database between January 1, 1990, and June 30, 1992. Complete HLA information on the A, B, and DR loci was available for both donor and recipient in 1190 patients. Of these, 619 (52%) had five or six mismatches; 68 (6%) had zero, one, or two mismatches. The mean number of mismatches was 4.4 and did not differ, regardless of donor-recipient race match (4.3 versus 4.8, p = 0.19). According to multivariate analysis, risk factors for time to first rejection included younger recipient age (p < 0.0001), female gender of both donor and recipient (p < 0.0006), number of HLA mismatches (p = 0.013) and black recipient race (p < 0.004). Patients with zero, one, or two mismatches (n = 67) had a 54% freedom from rejection at 1 year versus 36% for patients with three or more mismatches (n = 1005, p = 0.02). HLA mismatch number did not affect time to first rejection or rejection frequency among black patients. Risk factors (by multivariate analysis) for death or retransplantation because of rejection included female recipient gender (p = 0.008) and black recipient race (p = 0.006). The probability of rejection-related death or retransplantation by 2 years was 0% with zero, one, or two HLA mismatches versus 5% for three to six mismatches (p = 0.14). These findings should stimulate further investigation of methods to clarify the HLA effect in heart transplantation and eventually the use of HLA typing in donor-recipient selection.

Actuarial Analysis↗

Matching the heart donor and heart transplant recipient. Clues for successful expansion of the donor pool: a multivariable, multiinstitutional report. The Cardiac Transplant Research Database Group.

Little information is available regarding donor-specific parameters that predict success or failure after heart transplantation. Furthermore, with increasing numbers of patients awaiting heart transplantation, there is tremendous pressure to expand the donor pool by stretching the margins of donor acceptability. To gain insight into donor-related and donor-recipient interrelated predictors of death after transplantation, 1719 consecutive primary transplantations performed at 27 institutions between Jan. 1, 1990, and June 30, 1992, were analyzed. Mean follow-up of survivors was 13.9 months, and actuarial survival was 85% at 1 year. By multivariable analysis, risk factors for death included younger recipient age (p = 0.006), older recipient age (p = 0.0005), ventilator support at time of transplantation (p = 0.0006), higher pulmonary vascular resistance (p = 0.02), older donor age (p < 0.0001), smaller donor body surface area (female donor heart placed into larger male patient) (p = 0.003), greater donor inotropic support (p = 0.01), donor diabetes mellitus (p = 0.01), longer ischemic time (p = 0.0003), diffuse donor heart wall motion abnormalities by echocardiography (p = 0.06), and, for pediatric donors, death from causes other than closed head trauma (p = 0.02). The overall 30-day mortality rate was 7% but increased to 11% when donor age exceeded 50 years and was 12% when inotropic support exceeded 20 micrograms/kg/min dopamine plus dobutamine and 22% with diffuse echocardiographic wall motion abnormalities. The interaction of donor risk factors was such that the heart of a smaller female donor given high-dose inotropes placed into a larger male recipient produced a predicted 30-day mortality rate of 26% and the heart of a 25-year-old male donor given high-dose inotropes with diffuse echocardiographic wall motion abnormalities transplanted into a 50-year-old male recipient led to a predicted 30-day mortality rate of 17%. This analysis supports cautious extension of criteria for donor acceptance but with an anticipated greater risk in the presence of diffuse echocardiographic wall motion abnormalities and long anticipated ischemic time, particularly in older donors given inotropic support.

Actuarial Analysis↗

Infection after heart transplantation: a multiinstitutional study. Cardiac Transplant Research Database Group.

The incidence, causes, and impact of acute infection were analyzed among 814 consecutive patients from 24 institutions undergoing primary heart transplantation between January 1, 1990, and June 30, 1991, with mean follow-up of 8.2 months (range 0 to 18 months). Sixty-nine percent of the patients had no infections during the follow-up, whereas 31% of patients had one or more infection episodes. The cumulative incidence of infections per patient was 0.41 at 3 months, 0.55 at 6 months, and 0.62 at 12 months after transplantation. Bacterial and viral infections were most common (47% and 41% of infections), with fungi and protozoa accounting for 12%. Overall mortality per infection was 13%, but mortality with fungal infections was higher (36%, p < 0.0001). The most common organ infected was the lung, with a mortality of 23%. The probability of infection by 12 months was higher when OKT3 or antithymocyte globulin induction therapy was used (41% versus 35%, p = 0.01). The single most frequent infecting organism was cytomegalovirus, accounting for 26% of all infections. The probability of cytomegalovirus infection by 12 months was increased with a cytomegalovirus-positive donor and cytomegalovirus-negative recipient (27% versus 15% in all others, p < 0.0001) and with the use of OKT3 or antithymocyte globulin induction therapy (19% versus 12% without induction therapy, p = 0.07). Infection remains the leading cause of death after heart transplantation. The hazard function of likelihood of developing each type of infection at various times after transplantation, as well as response to therapy, are discussed.

Adolescent↗

Cytomegalovirus after heart transplantation. Risk factors for infection and death: a multiinstitutional study. The Cardiac Transplant Research Database Group.

Cytomegalovirus infection is a major cause of morbidity and rehospitalization after heart transplantation. To assess its incidence and risk factors in the current era of heart transplantation, we analyzed cytomegalovirus infection data in 1553 patients from 26 institutions (Cardiac Transplant Research Database Group) undergoing primary heart transplantation between Jan. 1, 1990, and June 30, 1992. There were 230 treated cytomegalovirus infections in 200 patients, of which 16 were fatal (6%; 70% confidence limits 5% to 9%). Actuarial freedom from cytomegalovirus infection was 98% 1 month, 88% 3 months, and 83% 24 months after transplantation, with a peak incidence of initial infection at 2 months. Twenty-five (12%) of 200 patients with cytomegalovirus infection had recurrent cytomegalovirus infection during a mean follow-up of 13.9 months. The primary location of cytomegalovirus infection was blood in 100 infections (43%), lung in 69 (30%), gastrointestinal tract in 54 (23%), and other sites in seven patients (3%). Cytomegalovirus pneumonia exhibited the highest mortality rate (13%). Risk factors by multivariate analysis for earlier development of cytomegalovirus infection included pretransplantation cytomegalovirus serology (positive donor, negative recipient [p < 0.0001]; positive donor, positive recipient [p = 0.0002]; and negative donor, positive recipient [p = 0.02]) and cytolytic induction therapy (p = 0.05). A cytomegalovirus-positive recipient with a cytomegalovirus-positive donor had a 15% chance of having cytomegalovirus infection, whereas a cytomegalovirus-negative recipient with a cytomegalovirus-positive donor had a 24% chance. Ganciclovir treatment was administered in 227 (99%) of 230 infections. By multivariable analysis, the likelihood of a fatal cytomegalovirus infection was increased with a higher number of infections of any type during the first post transplantation month (p < 0.0001). There was no increased mortality rate in cytomegalovirus infections associated with cytomegalovirus-positive donor and cytomegalovirus-negative recipient (6% mortality rate) versus all other cytomegalovirus infections (6% mortality rate) (p = 0.9) or with OKT3 induction therapy (0% mortality rate) versus all others (noninduction and induction with other than OKT3) (1.4%) (p = 0.03). In conclusion, the biggest determinant of cytomegalovirus infection is donor and recipient pretransplantation cytomegalovirus serologic results with cytolytic induction therapy adding a small additional risk. The overall mortality rate from cytomegalovirus infections is low (7%) in the current era with rapid culture techniques and ganciclovir therapy. Cytomegalovirus infections are more likely to be fatal if there are more frequent preceding infections of any type, but mortality rates are not increased by OKT3 induction or with a cytomegalovirus-positive donor organ transplanted into a cytomegalovirus-negative recipient.

Adolescent↗

Treatment of recurrent heart rejection with mycophenolate mofetil (RS-61443): initial clinical experience.

Mycophenolate mofetil (RS-61443), a derivative of mycophenolic acid, is a new immunosuppressive agent that inhibits de novo purine synthesis in activated lymphocytes. In a clinical trial of mycophenolate mofetil in the treatment of recurrent or persistent heart rejection, 17 patients 0.6 to 104 months (median 5.4 months) after transplantation received a daily oral dose of mycophenolate mofetil of 3000 mg, with seven patients increasing to 3500 mg daily. Azathioprine was routinely discontinued at the start of mycophenolate mofetil treatment. One patient in shock from acute rejection required retransplantation before starting mycophenolate mofetil and died 68 days later of cytomegalovirus sepsis. Another patient died 72 days after mycophenolate mofetil of protracted multisystem failure (present before mycophenolate mofetil). One patient required early cessation of mycophenolate mofetil, and the other 14 patients were alive and well 5 to 10 months after initiating mycophenolate mofetil treatment. Three patients required transient dose reduction and one patient required discontinuation of mycophenolate mofetil because of nausea, diarrhea, or abdominal cramps. No other clinical side effects were noted. Frequency of rejection decreased from 0.67 rejection episodes per patient per month before mycophenolate mofetil to 0.27 rejection episodes per patient per month after mycophenolate mofetil (p < 0.0001). Frequency of infection was unchanged after mycophenolate mofetil (p = 0.9). Renal function was not affected by mycophenolate mofetil (creatinine clearance 1.8 mg/dl before mycophenolate mofetil vs 1.7 mg/dl after mycophenolate mofetil; p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Total lymphoid irradiation: is there a role in pediatric heart transplantation?

Total lymphoid irradiation (TLI) is an effective adjunct in the therapy of recurrent allograft rejection in adult patients. Between Jan. 3, 1990, and Feb. 5, 1992, TLI was used in 43 heart transplant patients 4 days to 67 months (mean, 6 months) after heart transplantation for recurrent allograft rejection. A mean TLI dose of 700 cGy (range, 40 to 1120 cGy-) was administered during a mean of 7 weeks with adjustment in overall dose and duration determined in part by leukopenia, thrombocytopenia, or both. Among patients who received TLI therapy within 1 month of transplantation (n = 12), the rejection rate decreased from 1.9 episodes per patient per month before TLI to 0.1 episodes per patient per month after TLI (p < 0.001). Sixty percent of patients had no further rejection episodes for 6 months after TLI. Peripheral blood mononuclear cells from two patients were specifically unreactive toward donor stimulator cells in mixed-lymphocyte cultures at 2.5 and 6 months after TLI. During this experience three pediatric patients (ages 10 to 17 years) received TLI at 0.5, 0.8, and 0.9 months after heart transplantation for recurrent allograft rejection. The total TLI dosage for each patient was 720, 800, and 800 cGy. The rejection frequency fell from 1.8 episodes per patient per month before TLI to 0.1 episodes after TLI (p < 0.01). During follow-up of 6 to 25 months after TLI, no adverse sequelae of TLI were identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Pretransplantation risk factors for acute rejection after heart transplantation: a multiinstitutional study. The Transplant Cardiologists Research Database Group.

To better understand the phenomenon of acute rejection in the current era of heart transplantation, complete rejection data (918 rejection episodes) from 25 institutions were analyzed for all 911 patients undergoing primary heart transplantation between January 1, 1990, and July 1, 1991. During a mean follow-up of 8.1 months (maximum, 18 months), 54% of the patients had one or more rejection episodes. The mean cumulative number of rejection episodes per patient was 0.8 at 3 months, 1.10 at 6 months, and 1.3 at 12 months after transplantation. By univariate analysis, female donor hearts (irrespective of recipient sex) (p < 0.01) and the use of induction therapy (p < 0.01) were associated with greater cumulative rejection frequency. By multivariate analysis, younger donor age and female donor gender were risk factors for earlier rejection. Solution of the multivariate equation predicted an 85% probability of rejection at 1 month for a 5-year-old female with a female donor and 50% for a 50-year-old man with a male donor. Inferences: (1) In the current era, over 40% of patients appear to be free of rejection during the first year after transplantation. (2) Younger recipient age and female donors are associated with earlier onset of allograft rejection, but the precise immunologic basis for these observations remains unknown. (3) In this experience, induction therapy did not delay the onset of first rejection nor did it reduce the cumulative number of rejection episodes. Further studies are indicated to examine the need for induction therapy.

Actuarial Analysis↗

Pretransplantation risk factors for death after heart transplantation: a multiinstitutional study. The Transplant Cardiologists Research Database Group.

Risk factors for death after heart transplantation were identified by analyzing the total primary heart transplantation experience (n = 911) among 25 institutions from January 1, 1990, through June 30, 1991. Overall actuarial survival was 93% at 1 month and 84% at 12 months. The hazard function for death was highest early after heart transplantation and fell rapidly over the first 6 months, with a gradually declining hazard thereafter. The two most common causes of death were infection (n = 29) and early graft failure (n = 28), accounting for 45% of the overall deaths. By multivariable analysis, risk factors for death during the study period included very young recipient age (p = 0.004), advanced age (p = 0.009), ventilator support at time of transplantation (p = 0.09), abnormal renal function (p = 0.1), lower pretransplantation cardiac output (p = 0.009), higher pulmonary vascular resistance in children (p = 0.006), longer donor ischemic time (p = 0.001), older donor age (p = 0.001), and donor and recipient not both blood type O (p = 0.009). The recipient age effect was greatest in patients under 5 years of age (1-year survival rate 68% versus 85% for all others, p = 0.002). Patients aged 60 years and older had a 1-year survival rate of 81%. Patients who were ventilator dependent at transplantation fared especially poorly, with a 3-month survival rate of 65%. Transplantation of a blood group O heart into a non-O recipient had a somewhat lower 1-year survival rate than did blood group O into an O recipient (82% versus 88%, p = 0.06). The adverse effect of a longer ischemic time was most notable after 4 hours (1-month survival rate 71% for more than 4 hours versus 85% for less than 4 hours, p = 0.0003). Inference: These multiinstitutional-derived risk factors for early-term death after heart transplantation may help improve patient and donor selection and focus further scientific investigations to increase the safety of heart transplantation.

Actuarial Analysis↗

Utility of posttransplantation panel-reactive antibody measurements for the prediction of rejection frequency and survival of heart transplant recipients.

BACKGROUND AND METHODS: Seventy-six heart transplants in 73 patients were studied for the formation of lymphocytotoxic panel-reactive antibodies after transplantation. Treatment of patient serum with dithioerythritol was used to discriminate between antibodies of the immunoglobulin M and immunoglobulin G isotypes. Human leukocyte antigen specificities of immunoglobulin G panel reactive antibodies were determined by the pattern of reactivity with the cell panel used in the panel-reactive antibodies determinations. A total of 465 panel-reactive antibodies determinations were made during the first year after transplantation. RESULTS: Mean panel-reactive antibodies values were highest during the first posttransplantation month. Positive dithioerythritol-treated panel-reactive antibodies values were rare after the first month after transplantation. Multivariable analysis indicated that previous pregnancy and positive cytomegalovirus serologic analysis predicted a higher dithioerythritol-treated panel-reactive antibodies within the first 3 months. No decrease in actuarial survival, increase in cumulative rejection episodes, or increase in the incidence of coronary artery disease at 1 year was seen in patients with a standard panel-reactive antibodies greater than 10% or among patients with dithioerythritol-treated panel-reactive antibodies greater than 0%. A significant and major increase in rejection-related death or retransplantation occurred among 11 patients in whom donor human leukocyte antigen specific antibodies of the immunoglobulin G isotype were detected during the first posttransplantation year (p = 0.02). Two of the 11 patients died of refractory rejection and 3 and 6 months after transplantation, whereas one patient underwent retransplantation for refractory rejection at 13 months and subsequently died. CONCLUSIONS: (1) Posttransplantation serial standard panel-reactive antibodies or dithioerythritol-treated panel-reactive antibodies are not predictive of rejection-related mortality unless the specificity is determined to be antidonor HLA; (2) routine dithioerythritol-treated panel-reactive antibodies studies are advisable during the first month after transplantation, and, if positive (> 10%), antidonor human leukocyte antigen specificity should be determined; (3) detection of recipient immunoglobulin G anti-donor human leukocyte antigen antibodies after heart transplantation identifies a group at high risk for serious allograft rejection and should prompt more intensive rejection surveillance and consideration for additional immunotherapy.

Actuarial Analysis↗