EBV PCR in the diagnosis and monitoring of posttransplant lymphoproliferative disorder: results of a two-arm prospective trial.

While EBV PCR is used in the management of PTLD, the optimal primer set, relative importance of intracellular versus free plasma EBV, and the baseline profile in an organ transplant population remains unclear. We performed a prospective 2-arm trial utilizing an EBV PCR panel measuring LMP-1, EBER-1 and EBNA-1 in both free plasma as well as intracellular whole blood. Control Arm A consisted of 31 lung transplant patients and Arm B consisted of 35 transplant patients being evaluated for possible PTLD. In Arm A, 1/31 (3%) patients developed a transient plasma EBV load. Thirteen of 31 (42%) had detectable intracellular EBV. In Arm B, 17 (49%) patients were diagnosed with PTLD. Thirteen (76%) had EBV-positive PTLD with 12/13 (92%) having detectable EBV by PCR. The EBV PCR panel had a high sensitivity (92%), specificity (72%), positive predictive value (PPV) (71%) and negative predictive value (NPV) (93%) for diagnosing EBV-positive PTLD and followed patients' clinical course well (p < 0.001). Comparing the individual PCR assays, plasma EBNA PCR was superior with high sensitivity (77%), specificity (100%), PPV (100%) and NPV (86%). We conclude that EBV PCR is a useful test for managing PTLD patients. While plasma EBNA PCR is the best single assay for diagnosing and monitoring PTLD, the complete PCR panel is superior for ruling out its presence.

A prospective cross-sectional study of BK virus infection in non-renal solid organ transplant recipients with chronic renal dysfunction.

BACKGROUND: Polyomavirus (primarily BK virus [BKV]) infection is an important cause of chronic renal dysfunction in renal transplant recipients, but its possible contribution to chronic renal dysfunction in non-renal solid organ transplant (NRSOT) recipients has not been fully explored. METHODS: We performed a prospective, cross-sectional study of consecutive NRSOT recipients with unexplained chronic renal dysfunction of at least a 3 months duration. Medical records were reviewed, and polymerase chain reaction was used to amplify BKV-specific sequences from serum and urine samples. The potential associations between various demographic and transplant variables and BKV infection were assessed. RESULTS: Thirty-four consecutive NRSOT recipients (23 lung, 8 liver, 2 heart, 1 heart-lung) with chronic renal dysfunction were enrolled at a median of 3.5 years (range 0.3-12.5 years) post transplantation. Five of the 34 (15%) patients had BKV viruria (range 1040-1.8 x 10(6) copies/mL), but none had BKV viremia. BK viruria was associated with mycophenolate mofetil use (5 of 19 [26%] vs. 0 of 15, P = 0.03) and a history of cytomegalovirus disease (3 of 4 [75%] vs. 2 of 30 [7%], P < 0.01). However, the mean estimated creatinine clearance was similar in patients with or without BKV viruria (49 vs. 47 mL/min). CONCLUSIONS: BKV viruria was present in a proportion of NRSOT patients with otherwise unexplained chronic renal dysfunction. The possibility that BKV infection might contribute to chronic renal dysfunction in this setting warrants further investigation.

Treatment of PTLD with rituximab or chemotherapy.

Information regarding treatment of post-transplant lymphoproliferative disease (PTLD) beyond reduction in immunosuppression (RI) is limited. We retrospectively evaluated patients receiving rituximab and/or chemotherapy for PTLD for response, time to treatment failure (TTF) and overall survival (OS). Thirty-five patients met inclusion criteria. Twenty-two underwent rituximab treatment, with overall response rate (ORR) 68%. Median TTF was not reached at 19 months and estimated OS was 31 months. In univariable analysis, Epstein-Barr virus (EBV) positivity predicted response and TTF. LDH elevation predicted shorter OS. No patient died of rituximab toxicity and all patients who progressed underwent further treatment with chemotherapy. Twenty-three patients received chemotherapy. ORR was 74%, median TTF was 10.5 months and estimated OS was 42 months. Prognostic factors for response included stage, LDH and allograft involvement by tumor. These factors and lack of complete response (CR) predicted poor survival. Twenty-six percent of the patients receiving chemotherapy died of toxicity. Rituximab and chemotherapy are effective in patients with PTLD who fail or do not tolerate RI. While rituximab is well tolerated, toxicity of chemotherapy is marked. PTLD patients requiring therapy beyond RI should be considered for rituximab, especially with EBV-positive disease. Chemotherapy should be reserved for patients who fail rituximab, have EBV-negative tumors or need a rapid response.

Immunogenicity of pneumococcal vaccine in heart transplant recipients.

To assess the immunogenicity of pneumococcal vaccine in recipients of heart transplants, we immunized 35 long-term transplantation survivors with pneumococcal vaccine and measured the pre- and postvaccination IgG antibody titers to 5 representative vaccine capsular polysaccharides. Responses of heart transplant recipients to pneumococcal vaccine antigens were generally suppressed.

Early detection of acute allograft rejection by linear and nonlinear analysis of heart rate variability.

OBJECTIVE: The first months after orthotopic heart transplantation are associated with the highest risk of acute allograft rejection. This study explores the utility and reliability of linear and novel nonlinear metrics of heart rate variability as predictors of graft rejection. The underlying hypothesis is that the transplanted heart, in response to inflammatory mediators, alters the dynamic properties of its rhythm-generating system. METHODS: In a cross-sectional study of 45 patients who had undergone heart transplantation, spanning a period of 4 months after the operation, heart rate variability was examined by time- and frequency-domain analysis. The nonlinear features of heart rate variability were studied by computing a pointwise correlation dimension of R-R interval time series. The results of heart rate variability analysis were compared with those of endomyocardial surveillance biopsy studies using the International Society for Heart and Lung Transplantation scoring system. RESULTS: Duration of heart transplantation itself exhibited a significant (P<.05) association with the onset of rejection. Specific predictors of acute rejection based on heart rate variability were identified, including shortening of the R-R interval (from 700 +/- 68 to 648 +/- 72 ms), an increase in the ratio of low-frequency (0.04-0.15 Hz) to high-frequency (0.15-0.40 Hz) spectral power (from 0.3 +/- 0.2 to 0.6 +/- 0.4), and a decrease in pointwise correlation dimension values (from 1.7 +/- 0.7 to 0.9 +/- 0.3 units). Multivariable logistic regression analysis (R (2) = 0.4) revealed that the only significant independent risk predictors were pointwise correlation dimension (odds ratio, 2.2 per 0.1 unit) and duration of heart transplantation (odds ratio, 1.7 per week). CONCLUSION: Nonlinear measures of heart rate variability provide noninvasive means for identifying patients undergoing cardiac transplantation with acute rejection, thereby enabling the assessment of the time-dependent adaptive response of the donor heart to its host.

Safety of influenza vaccine in heart transplant recipients.

BACKGROUND: Influenza vaccine is recommended for heart transplant recipients, but its administration is often deferred because of anecdotal reports of rejection associated with the vaccine. We evaluated the safety of influenza vaccine in a group of stable heart transplant recipients over a 2-year period. METHODS: During the 1993 to 1994 influenza season, stable heart transplant recipients who had undergone transplantation a minimum of 1 year before study entry were randomized to vaccination with a single dose of influenza vaccine versus no vaccination. Routine endomyocardial biopsies and postvaccination influenza serologic studies were performed between 2 and 6 weeks after enrollment/immunization. During the 1994 to 1995 season, patients were given 2 doses of influenza vaccine, separated by 3 weeks; endomyocardial biopsies and serologic studies were performed between 2 and 6 weeks after the second immunization or enrollment (if control subject). Biopsy results were evaluated with respect to vaccine response, immunosuppressive regimens, and patient demographics. RESULTS: Eighteen patients were enrolled in the single vaccine trial and 10 in the booster vaccine trial. Four of 14 vaccine recipients had biopsy specimens consistent with International Society for Heart and Lung Transplantation grades 2 to 3A as compared with 1 of 14 control subjects (grade 2) (p = .326). All episodes of rejection in the vaccine recipients were asymptomatic and responded to a single course of treatment. Rejection was unrelated to the time from transplantation, doses of immunosuppression, age, or number of doses of or response to vaccine. CONCLUSIONS: Influenza vaccine can be safely administered to most heart transplant recipients but may be associated with low-level histologic rejection.

Heart transplant coronary artery disease detected by coronary angiography: a multiinstitutional study of preoperative donor and recipient risk factors. Cardiac Transplant Research Database.

BACKGROUND: Controversy exists regarding donor and recipient factors that promote the development and progression of coronary artery disease after heart transplantation and the likelihood of coronary artery disease causing death or retransplantation. METHODS: To investigate this issue in a large cohort of patients, we analyzed 5963 postoperative angiograms performed in 2609 of the 3837 patients undergoing heart transplantation at 39 institutions between January 1990 and December 1994. Coronary artery disease was classified as mild, moderate, or severe on the basis of left main involvement, primary vessel stenoses, and branch stenoses. Coronary artery disease was considered severe if left main stenosis was > 70% or 2 or more primary vessels stenoses were > 70% or branch stenoses were > 70% in all 3 systems. RESULTS: By the end of 5 years after heart transplantation, coronary artery disease was present in 42% of the patients, mild in 27%, moderate in 8%, and severe in 7%. Coronary artery disease-related events (death or retransplantation) had an actuarial incidence of 7% at 5 years and occurred in 2 of 3 of the patients with development of angiographically severe coronary artery disease. By multivariable logistic analysis, risk factors for donor coronary artery disease included older donor age (P < .0001) and donor hypertension (P=.0002). By multivariable analysis in the hazard function domain, risk factors identified for the earlier onset of allograft coronary artery disease included older donor age (P < .0001 ), donor male sex (P=.0006), donor hypertension (P=.07), recipient male sex (P=.02), and recipient black race (P=.01). The actuarial incidence of severe coronary artery disease was 9% at 5 years. CONCLUSIONS: Angiographic coronary artery disease is very common after heart transplantation, occurring in approximately 42% of the patients by 5 years. Older donor age, donor hypertension, and male donor or recipient predict earlier onset of angiographic allograft coronary artery disease. Although severe angiographic allograft coronary artery disease occurs in only 7% of the patients at 5 years, its presence is highly predictive of subsequent coronary artery disease-related events or retransplantation.

Heart transplantation in patients with heparin-induced thrombocytopenia on the Novacor left ventricular assist system.

We report on two patients with development of heparin-induced thrombocytopenia with thrombosis while on the Novacor left ventricular assist system. Heart transplantation was successfully performed in both patients with heparin used for cardiopulmonary bypass after careful monitoring of heparin-associated antibodies. The approach to the patients' management and potential alternatives for anticoagulation are discussed.

Exercise-induced ventilatory abnormalities in orthotopic heart transplant patients.

STUDY OBJECTIVE: The purpose of this investigation was to compare multiple ventilatory responses of heart transplant patients (HTP) with normal subjects (NL) at rest, at absolute and relative submaximal exercise levels, and at peak exercise. DESIGN: Ten male HTP and 10 matched NL were tested under similar conditions on a treadmill with the use of an incremental protocol to symptom-limited maximal levels while breath-by-breath measurements of gas exchange and ventilation were obtained. RESULTS: At an absolute carbon dioxide (VCO2) level of 1 L.min-1, minute ventilation (VE) was significantly higher in HTP compared with NL (38.4 +/- 1.9 versus 29.3 +/- 0.9 L.min-1). However, when compared at similar relative levels (i.e., 40% and 60% of the peak oxygen consumption [VO2 peak]), VE was found to be significantly higher in NL compared with HTP (25.5 +/- 1.4 versus 21.2 +/- 1.0 L.min-1 at 40%; 39.9 +/- 3.1 versus 32.1 +/- 2.0 L.min-1 at 60%, respectively). The reduced VE was the result of a significantly lower tidal volume (VT) in HTP compared with NL at 40% (1.14 +/- 0.08 versus 1.33 +/- 0.05 L) and 60% (1.40 +/- 0.10 versus 1.85 +/- 0.06 L) of VO2 peak, since breathing frequency (BF) was not different between the groups at these levels. CONCLUSIONS: These data demonstrate that HTP have abnormal ventilatory responses to incremental exercise that are largely explained by a diminished VT response. While mechanical factors known to affect VT cannot be ignored, it is likely that the abnormal VT response of HTP during exercise is secondary to respiratory muscle weakness and may be due to hypoperfusion, long-term deconditioning, and/or the long-term use of corticosteriods.

Effectiveness and safety of diltiazem or lisinopril in treatment of hypertension after heart transplantation. Results of a prospective, randomized multicenter trail.

OBJECTIVES: The purpose of this study was to determine the effectiveness and safety of diltiazem or lisinopril for treatment of hypertension after heart transplantation. BACKGROUND: Systemic hypertension is common after heart transplantation, and to date there are no randomized, prospective multicenter treatment trials. METHODS: Members of the Cardiac Transplant Research Database Group developed and implemented a prospective, randomized multicenter trial of the effectiveness and safety of diltiazem or lisinopril in the treatment of hypertension in cyclosporine-treated patients after heart transplantation. RESULTS: One hundred sixteen patients with hypertension (blood pressure > or = 140/90 mm Hg) after heart transplantation were randomized for > or = 3 months of treatment. Of 55 diltiazem-treated patients, 21 (38%) were responders (diastolic blood pressure < 90 mm Hg), 23 (42%) were nonresponders (diastolic blood pressure > or = 90 mm Hg), and 11 (20%) were withdrawn from the study. Of 61 lisinopril-treated patients, 28 (46%) were responders, 22 (36%) were nonresponders, and 11 (18%) were withdrawn. There was no difference in baseline characteristics or percent responders between the two groups. Systolic pressure decreased from 157 +/- 2.3 to 130 +/- 2.0 mm Hg (mean +/- 1 SEM) in the diltiazem-treated responders and from 153 +/- 2.1 to 127 +/- 2.7 mm Hg in the lisinopril-treated responders (p < 0.0001). Diastolic pressure decreased from 100 +/- 0.9 to 85 +/- 1.6 mm Hg in the diltiazem-treated responders and from 100 +/- 1.0 to 84 +/- 2.0 mm Hg in the lisinopril-treated responders (p < 0.0001). There were a total of 35 reported adverse events, 22 of which led to withdrawal of the patient from the study. All drug-related side effects were considered minor and resolved with discontinuation of the drug. CONCLUSIONS: These results indicate that both diltiazem and lisinopril are safe for treatment of hypertension after heart transplantation, although titrated monotherapy with either drug controlled the condition in < 50% of patients.

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.

Serum myoglobin does not predict cardiac allograft rejection.

Noninvasive studies are useful, but limited, in detecting rejection among cardiac allograft recipients. Because an elevated serum myoglobin level is a sensitive indicator of necrosis in acute myocardial infarction, we postulated that myoglobin levels might correlate with the presence, absence, or degree of rejection. Therefore we prospectively measured serum myoglobin levels at the time of endomyocardial biopsy in 45 heart transplant recipients and correlated these levels with biopsy scores (grade 0 through grade 4). There was no significant difference in mean myoglobin levels among patients with grade 0 biopsy scores and those with grade 1 through grade 4 scores. Serial myoglobin levels and endomyocardial biopsy specimens were obtained in five patients during a 4- to 9-week period; no significant directional change in myoglobin levels appeared to correlate with changes in endomyocardial biopsy score. In addition, a normal myoglobin level did not exclude, nor did an elevated level confirm, any grade of rejection. We conclude that neither the absolute level nor a directional change in serum myoglobin is useful in identifying rejection among heart transplant recipients.

Assessing risk by hemodynamic profile in patients awaiting cardiac transplantation.

A profile of hemodynamic abnormalities in patients listed for cardiac transplantation was related to survival during the first year after listing. After a patient is listed for cardiac transplantation, the waiting period for a suitable donor heart is often long; therefore, objective criteria to determine risk would be helpful in identifying the group at highest risk of dying before receiving a transplant. Several studies have suggested certain hemodynamic parameters to be related to a poor prognosis. However, no 1 variable has emerged as an adequate predictor of survival in patients awaiting cardiac transplantation. One-year outcomes were examined in 138 consecutive patients listed for cardiac transplantation, who were grouped according to a hemodynamic risk score (HRS) based on abnormalities in baseline measures of right atrial pressure, pulmonary artery systolic pressure, transpulmonary gradient, cardiac output, cardiac index and pulmonary vascular resistance. Right atrial pressure alone was the most significant predictor of survival (p < 0.05). Patients with a right atrial pressure > 12 mm Hg had a 47% 1-year survival as compared with the 68% survival for those with a right atrial pressure < 12 mm Hg. HRS was the next strongest predictor of survival. The 66% survival in group I (HRS = 0) and the 69% survival in group II (HRS = 1 to 3) were significantly (p < 0.03) higher than the 41% survival in group III (HRS = 4 to 6) at 1 year after listing. Differences in survival for the HRS groups could not be explained by left ventricular ejection fraction, left ventricular end-diastolic diameter or status at listing.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of phosphodiesterase inhibition with milrinone in combination with converting enzyme inhibitors in patients with heart failure. The Milrinone Multicenter Trials Investigators.

We describe the results of two placebo-controlled trials (MIL-1077 and MIL-1078) designed to evaluate the clinical efficacy of oral milrinone administered together with converting enzyme inhibitors to patients with congestive heart failure. Although these trials were terminated prematurely, they provide the only controlled data regarding the effect of oral milrinone on exercise capacity in patients receiving converting enzyme inhibitors. Of the 254 patients randomized, 140 completed one of the trials or reached an end point and are the basis of this report. In both trials, there was a clear trend for an increase in exercise capacity in the milrinone-treated patients (+26 +/- 8% vs. +5 +/- 7% in MIL-1077 and +11 +/- 5% vs. +2 +/- 4% in MIL-1078). Symptoms of congestive heart failure were decreased in one trial but not the other. Quality of life, as assessed by a questionnaire, was not effected in either trial. There was an increased incidence of adverse events in milrinone-treated patients. Adverse events related primarily to hypotension and vasodilation led to discontinuation of drug in 18 milrinone-treated patients vs. 1 placebo-treated patient. Milrinone had little or no proarrhythmic effect and cardiovascular deaths were distributed equally between the milrinone and placebo groups. These data suggest that when used in combination with a converting enzyme inhibitor, oral milrinone improves exercise capacity but is associated with a high incidence of adverse events that appear to be related to excessive vasodilation.

Can further benefit be achieved by adding flosequinan to patients with congestive heart failure who remain symptomatic on diuretic, digoxin, and an angiotensin converting enzyme inhibitor? Results of the flosequinan-ACE inhibitor trial (FACET).

BACKGROUND: Angiotensin converting enzyme inhibitors, diuretics, and digoxin are each effective in treating congestive heart failure, but many patients remain symptom-limited on all three medications. This trial was designed to determine whether the addition of oral flosequinan, a new direct-acting arterial and venous vasodilator with possible dose-dependent positive inotropic effects, improves exercise tolerance and quality of life in such patients. METHODS AND RESULTS: In a randomized, double-blind multicenter trial, 322 patients with predominantly New York Heart Association class II or III congestive heart failure and left ventricular ejection fractions of 35% or less, who were stabilized on a diuretic, angiotensin converting enzyme inhibitor, and digoxin, were treated with 100 mg flosequinan once daily, 75 mg flosequinan twice daily, or matching placebo. Efficacy was evaluated with serial measurements of treadmill exercise time, responses to the Minnesota Living With Heart Failure Questionnaire (LWHF), and clinical assessments during a baseline phase and a 16-week treatment period. After 16 weeks, 100 mg flosequinan once daily produced a significant increment in median exercise time (64 seconds at 16 weeks) compared with placebo (5 seconds), whereas the higher-dose flosequinan group did not show a statistically significant increase. Flosequinan (100 mg once daily) also improved the overall LWHF score significantly compared with placebo; both active therapies decreased the physical component, but 75 mg flosequinan twice daily was associated with a trend toward worsening of the emotional component. Most clinical assessments tended to improve on active therapy. CONCLUSIONS: These results indicate that additional symptomatic benefit can be attained by adding flosequinan to a therapeutic regimen already including a converting enzyme inhibitor. Because in the future most patients will fall into this category, flosequinan is a potential adjunctive agent in the management of severe congestive heart failure. However, because recent evidence indicates that the flosequinan dose studied in the present trial has an adverse effect on survival, the benefit-to-risk ratio must be assessed in individual patients.

Relationship of lactate and ventilatory thresholds in cardiac transplant patients.

The ventilatory threshold (VT) has been suggested as a method for determining exercise training intensity in cardiac transplant patients (CTPs). Since the VT has not been validated against the more accepted marker of the anaerobic threshold, the lactate threshold (LT), in CTPs, the purpose of this investigation was to compare the VT to the LT within, as well as between, CTPs and normal subjects (NLs). Ten male orthotopic CTPs and 10 age, size, and gender matched NLs were exercised to symptom-limited maximal levels following incremental treadmill protocols. The VT was determined using the V-slope method, and the LT was identified using the log-log transformation method. The NLs and significantly higher absolute levels of VO2 at both the VT (1298.6 +/- 78.5 vs 919.0 +/- 57.2 ml.min-1) and LT (1561.1 +/- 144.2 vs 921.6 +/- 47.6 ml.min-1) compared with the CTPs. However, there was no significant difference in the relative VO2 (% peak) between CTPs and NLs at the VT (57.2 +/- 3.0 vs 49.0 +/- 3.5%) or LT (58.2 +/- 3.3 vs 58.5 +/- 4.9%), respectively. Within groups there was no significant difference between the VT and LT for either CTPs (919.0 +/- 57.2 vs 921.6 +/- 47.6 ml.min-1 or NLs (1298.6 +/- 78.5 vs 1561.1 +/- 144.2 ml.min-1). From the results of this investigation it appears that the VT may be used as an indicator of LT in CTPs and is within a range acceptable for clinical application.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification and management of potential heart transplant recipients.

Transplantation should be performed to improve the quality and duration of life in patients with end-stage cardiac disease. Symptoms, left ventricular ejection fraction, previous and present medications, and an exercise tolerance test serve as basic screening information to identify potential transplant candidates. Patients need to have a psychological, financial, and behavioral profile that will allow them to withstand the rigors of the entire transplantation process, and have no other medical problems that would jeopardize their survival following transplant surgery. Maintenance of the patient's status while awaiting a cardiac donor begins with patient education and a search into the causes of underlying ventricular dysfunction. Medications subsequently used include diuretic agents, vasodilators, digitalis, anticoagulants, antiarrhythmics, and possibly beta-blocker therapy. When standard measures fail, potent inotropes and even mechanical assist devices are sometimes necessary. Future donor heart allocations will require more rigid criteria for the selection of cardiac transplant candidates.

Cognitive function in patients with symptomatic dilated cardiomyopathy before and after cardiac transplantation.

Pre- and postoperative cognitive performance of candidates for heart transplantation was examined by means of an extensive battery of neuropsychological measures. A total of 54 patients completed the preoperative cognitive protocol, 20 of whom also completed postoperative testing. Age (less than 50 or greater than or equal to 50 years of age) and the primary cause of cardiac deterioration (idiopathic, ischemic disease or rheumatic/congenital defects) were the major classification variables. The main findings of this study were: 1) Preoperative neuropsychological measures revealed a high frequency of impaired performance, particularly in measures of memory, higher level processing of information and motor speed. A pattern consistent with diffuse rather than focal or lateralized cerebral deficits was observed. Significant differences were not found on the basis of the cause of cardiac disease, but some were observed for age (the older group was more impaired). 2) A comparison of pre- and postoperative cognitive scores failed to show significant cognitive improvement despite greatly improved physical health. The cause of cardiac deterioration was not differentially associated with postoperative cognitive performance, and there was equivocal evidence for age effects. These findings may have implications for the selection of transplant recipients and the timing of transplantation surgery.