Incidence and prognostic significance of intraventricular conduction abnormalities after coronary bypass surgery.

To determine the incidence and prognostic significance of new postoperative conduction disturbances, 2,000 consecutive patients who underwent primary elective coronary bypass surgery were evaluated. One hundred eleven (5.5%) of the 2,000 patients developed a new intraventricular conduction defect that persisted to hospital discharge. Right bundle branch block occurred in 86 (85%), left bundle branch block in 5 (4%) and nonspecific intraventricular conduction defect in 9 (11%). One hundred of these 111 patients were successfully matched with others in the study population who had maintained normal intraventricular conduction during the operative period. Patients were matched on the basis of age, gender, absence of preoperative conduction disturbances, left ventricular function and bypass grafts to the same vessels. Follow-up of the two groups for a period of 1 to 76 months (mean 60 months) failed to show any difference in survival or cardiac events such as myocardial infarction, repeat coronary bypass surgery, coronary angioplasty and permanent pacemaker implantation. The appearance of right or left bundle branch block or a nonspecific intraventricular conduction defect after coronary bypass surgery does not appear to have an unfavorable impact on the long-term prognosis of these patients.

Results of partial left ventriculectomy for dilated cardiomyopathy: hemodynamic, clinical and echocardiographic observations.

OBJECTIVES: The study was done to prospectively measure the echocardiographic, hemodynamic and clinical outcomes after partial left ventriculectomy (PLV). BACKGROUND: Although PLV can improve symptoms of advanced heart failure, immediate postoperative echocardiographic findings remain abnormal. METHODS: Fifty-nine patients with cardiomyopathy and advanced heart failure underwent PLV and concomitant mitral valve surgery between May 1996 and December 1997. Thirty-nine percent were on inotropic therapy. All were New York Heart Association (NYHA) functional class III or IV. Mechanical circulatory support (LVAD) and transplant were provided for rescue therapy when hemodynamic compromise occurred. Patients were followed for a mean of 405+/-168 days, and clinical, echocardiographic and hemodynamic measures were obtained preoperatively, immediately postoperatively, and at 3 and 12 months prospectively. RESULTS: Comparing preoperative and 12-month postoperative values in event-free survivors, we found: NYHA functional class improved from 3.6 to 2.1, p < 0.0001; peak oxygen consumption increased from 10.8 to 16.0 ml/kg/min, p < 0.0001; LV ejection fraction increased from 13+/-6.0% to 24+/-6.9%, p < 0.0001; LV end diastolic diameter decreased from 8.2+/-1.03 to 6.2+/-0.64 cm, p < 0.0001, and volume was reduced from 167+/-60 to 105+/-38 ml/m2, p = 0.02. Central hemodynamics did not normalize after surgery. CONCLUSIONS: Partial left ventriculectomy can provide structural remodeling of the heart that may result in temporary improvement in clinical compensation. However, perioperative failures and the return of heart failure limit the propriety of this procedure.

Marfan's syndrome: natural history and long-term follow-up of cardiovascular involvement.

A retrospective analysis was undertaken to define the natural history and long-term follow-up of a group of patients with Marfan's syndrome. Eighty-four patients were diagnosed between January 1959 and June 1987 as having Marfan's syndrome; 68% were male; their ages ranged from 2 to 67 years (mean 26.6). Sixteen patients constituted the early surgical group (those who underwent surgery before 1979; mean age 36.1 years). Nineteen patients constituted the late surgical group (surgery in 1979 or later; mean age 33.3 years). The nonsurgical group comprised 49 patients (mean age 19.3 years). Fifty-seven percent of the patients had a diastolic murmur and 38% had cardiomegaly at presentation. Fifty-seven percent underwent cardiac catheterization, which revealed aortic root dilation (85%), aortic regurgitation (73%), aortic dissection (33%) and mitral regurgitation (36%). Thirteen of the 19 patients in the late surgical group received a composite graft repair of the ascending aorta as compared with only 2 of the 16 in the early surgical group. Follow-up information was obtained on 81 (96%) of 84 patients; the follow-up time was 2 to 332 months (mean 99). Thirty-one of the 81 patients died at age 3 to 63 years (mean age 35 years); 87% of the known causes of death were related to the cardiovascular system. Sixty-one percent of deaths were the result of aortic dissection or rupture or sudden cardiac death. Of the 50 survivors, 98%, including all patients in the late surgical group, were in functional class I or II. Overall survival at 5, 10 and 15 years after operation was 78.4%, 57.1% and 49.5%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Young adults with coronary atherosclerosis: 10 year results of surgical myocardial revascularization.

This study reviews data on 107 patients, aged 35 years or younger, who underwent surgical coronary revascularization from 1971 to 1975. Early clinical events included one operative death and five nonfatal perioperative myocardial infarctions. Late follow-up (mean interval after operation 115 months) demonstrated actuarial survival rates of 94% at 5 years and 85% at 10 years. Fifteen late deaths, 23 nonfatal myocardial infarctions, 13 reoperations and return of severe angina in 10 patients were considered late clinical events. Actuarial survival free of early or late clinical events was 77% at 5 years and 53% at 10 postoperative years. Testing of clinical, angiographic and operative variables for influence on survival and event-free survival showed that survival was decreased by multivessel disease and impaired left ventricular function; event-free survival was decreased by a family history of coronary disease and cigarette smoking. Both survival and event-free survival were decreased by diabetes and elevated serum cholesterol. Postoperative cardiac catheterization (64 patients, mean postoperative interval 47 months) demonstrated that mammary artery graft patency (25 of 27, 93%) exceeded vein graft patency (49 of 88, 56%, p less than 0.01). The atherogenic diatheses of young adults may compromise the operative result, whereas use of internal mammary artery grafts may enhance the palliation of bypass surgery.

The dilemma of diagnosing coronary calcification: angiography versus intravascular ultrasound.

OBJECTIVES: We sought to determine whether careful examination of angiograms in conjunction with other clinical information could reliably detect, quantitate and localize target lesion calcification before a coronary intervention. BACKGROUND: The presence, extent and location of calcium in coronary artery lesions are important determinants of outcome after coronary intervention. Intravascular ultrasound is proposed as a superior technique for identifying patients with coronary artery calcification. However, the precise role of this costly and invasive method has not yet been established. METHODS: Target lesion calcification was assessed in 183 patients (155 men; mean [+/-SD] age 58 +/- 10 years) by angiography and intravascular ultrasound before a planned percutaneous coronary intervention. RESULTS: Ultrasound detected calcium in 138 patients (>90 degrees in 56, 91 degrees to 180 degrees in 52, 181 degrees to 270 degrees in 22 and > 270 degrees in 8), whereas angiography showed calcification in 63 (1+ in 32, 2+ in 27 and 3+ in 4). The two techniques agreed in 92 patients and disagreed in 91. Sensitivity and specificity of angiography were 40% and 82%, respectively. The arc of calcium by ultrasound was greater in patients with angiographically visible calcification (175 degrees +/- 85 degrees vs. 108 degrees +/- 71 degrees, p=0.0001). The depth of calcification by ultrasound was superficial in 61 patients (44%), deep in 68 (49%) and mixed in 8 (7%). The sensitivity of angiography in identifying superficial calcium was 35%. Of 120 patients without angiographically visible calcium at the target lesion site, 83 showed calcium by ultrasound. The only predictor of ultrasound calcium in these 120 patients was angiographic calcification elsewhere in the coronary tree (p=0.0001). The probability of any calcium and superficial >90 degrees calcium were 60% and 12%, respectively, in the 90 patients without angiographic calcifications anywhere in the coronary tree. CONCLUSIONS: Despite poor sensitivity, angiography may help identify patients requiring intravascular ultrasound. When it is angiographically visible, the arc of calcium is likely to be large and superficial. Angiographic calcification at a remote site is a predictor of angiographically undetected target lesion calcium. Patients without angiographic calcification in the coronary tree may not need routine ultrasound examination, as the likelihood of >90 degrees superficial calcium is low.

Dichotomous pattern of coronary atherosclerosis 1 to 9 years after transplantation: insights from systematic intravascular ultrasound imaging.

OBJECTIVE: The aim of this study was to evaluate the extent and distribution of coronary atherosclerosis after transplantation. BACKGROUND: Transplant coronary artery disease is an important cause of death after cardiac transplantation. Unlike coronary angiography, intravascular ultrasound is a sensitive tool for detection and quantitation of this disease. METHODS: We performed intravascular ultrasound imaging in 132 (106 men, 50 +/- 10 years) patients, 1 to 9 years after transplantation using a 30-MHz ultrasound catheter. RESULTS: All three coronary arteries were visualized in 49, two in 62 and one in 21 patients. Of the 1,188 coronary artery segments, 706 were imaged (74% proximal, 64% mid- and 40% distal). At least one site with atherosclerosis (intimal thickness > or = to 0.5 mm) was found in 83% of patients. Atherosclerosis was noted in 64% of proximal, 43% of mid- and 26% of distal segments. Disease was diffuse in 48% and focal in 52%, circumferential in 66% and noncircumferential in 34%. Focal atherosclerosis was more common in proximal (59%) than mid- (48%) and distal segments (27%) (p=0.001). Noncircumferential plaques were more common in the proximal (42%) than mid- (28%) and distal segments (12%) (p=0.001). This pattern of focal and noncircumferential disease proximally, diffuse and circumferential disease distally, was observed irrespective of the time from transplantation. CONCLUSION: Atherosclerosis was detected in more than 80% of patients, with proximal segments most frequently involved. Diffuse and circumferential atherosclerosis was more common in mid- and distal segments. However, focal and noncircumferential involvement was more frequent proximally, a similar pattern to native atherosclerosis. These findings suggest that transplant coronary artery disease has a dual etiology based on the dichotomous pattern of atherosclerosis seen by intravascular ultrasound.

Cystic medial necrosis of the aorta in patients without Marfan's syndrome: surgical outcome and long-term follow-up.

A retrospective analysis was performed to determine the surgical outcome and long-term follow-up of patients with documented cystic medial necrosis of the aorta. Ninety-three patients were diagnosed as having cystic medial necrosis at the Cleveland Clinic between July 1963 and December 1987 (72% men aged 26 to 77 years, mean 55). Patients who met the standard diagnostic criteria for Marfan's syndrome were deliberately excluded. Sixty-eight percent of the patients had a diastolic murmur and chest roentgenogram revealed a dilated aortic arch in 58% and cardiomegaly in 63%. Cardiac catheterization in 76 patients demonstrated aortic root dilation in 78%, aortic regurgitation in 72%, aortic dissection in 32% and coronary artery disease in 32%. Ninety patients underwent surgery including composite graft repair with reimplantation of the coronary arteries in 34%. Follow-up, obtained on 90 (97%) of the 93 patients, ranged in duration from 0 to 137 months (mean 29). Thirty-four of the 90 patients died (age range 30 to 75 years, mean 60). Ninety-four percent of the known causes of death were related to the cardiovascular system; 65% were the result of aortic dissection or rupture or sudden death. Ninety-six percent of survivors were in New York Heart Association functional class I or II. Overall estimated survival at 1, 3 and 5 years was 72.2%, 63.5% and 57.4%, respectively. Actuarial survival in patients who underwent composite graft reconstruction was 84% at 5 years. The presence of a diastolic murmur at initial presentation was associated with a poor prognosis (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of frequency, time interval from initial instruction, and method of instruction on performance competency for blood glucose monitoring.

In a sample of 178 nurses who had been instructed in the performance of fingerstick monitoring of blood glucose (MBG), we investigated variables that may predict their proficiency at subsequent MBG performance. All nurses were given initial instruction in a classroom-type setting or via a self-instructional packet, and initial proficiency was documented by initial testing. All nurses were retested 1-8 mo later. To address whether actual frequency of performing MBG at work affected proficiency, the nurses were categorized based on the frequency of performing MBG groups: greater than 1 test/day (n = 53), greater than 1 test/wk (n = 51), greater than 1 test/mo (n = 52), and less than 1 test/mo (n = 22). No differences in test and retest scores were detected. To address whether the time interval from the original instruction and test to the retest affected proficiency, the nurses were divided into groups who had initial test less than 6 mo (n = 108) and greater than 6 mo (n = 70) before the retest. Mean change in test scores was less in the greater than 6-mo group than in the less than 6-mo group (P less than 0.01), and they had a lower retest fail rate (3 vs. 12%, P = 0.03). To explain this unexpected finding, test scores were analyzed by groups based on the type of original instruction. Nurses who attended class (n = 79) were compared with those who had self-instruction (n = 99). The classroom-trained group had less change in test-to-retest score (P = 0.0002) and a lower retest failure rate (3 vs. 12%, P less than 0.05).

A simplified method of CD34+ cell determination for peripheral blood progenitor cell transplantation and correlation with clinical engraftment.

Enumeration of CD34+ cells by flow cytometry is the recognized standard for quantitating progenitor cells for peripheral blood progenitor cell (PBPC) transplantation. Although many clinical studies have confirmed that the time to neutrophil and platelet engraftment is inversely proportional to the number of CD34+ cells infused, the minimum number of CD34+ cells necessary to acheive rapid engraftment has not been satisfactorily determined. The lack of a standardized method for quantitation of CD34+ cells by flow cytometry (FCM) is often cited as the reason for this ambiguity. This report describes an FCM method for CD34+ cell determination that is simple, highly reproducible, comparatively inexpensive, and validated by excellent correlation with clinical engraftment. Pheresis samples are stained and fixed within 4 hours of collection. Two hundred fifty thousand events are acquired as list mode data using a forward scatter threshold. The discrete CD34+ population is enumerated using a CD34-phycoerythrin FL2 vs. side scatter plot and Paint-A-Gate Pro software. The method was validated by excellent statistical correlation with clinical engraftment. Using this method, we determined the number of CD34+ progenitor cells necessary to achieve rapid engraftment to be 2 x 10(6)/kg.

Basal levels of plasma epinephrine and norepinephrine in the dog.

Conscious (n = 62) and anesthetized (n = 34) dogs were studied to establish basal levels and ranges for plasma epinephrine (E) and norepinephrine (NE) in this species. Trained conscious dogs were familiarized to recording conditions and personnel for 2 to 3 weeks and acclimatized to the laboratory for at least 15 minutes prior to blood sampling from a chronically implanted catheter. Their basal values were 65 +/- 47 pg/ml for E and 145 +/- 58 pg/ml for NE, which were significantly lower (p less than 0.05) than values in a second group of conscious dogs trained in the same manner but sampled soon after arrival to the laboratory (E = 144 +/- 93 pg/ml; NE = 193 +/- 86 pg/ml). Catecholamine levels in dogs anesthetized with one of three different regimes commonly used in cardiovascular studies were shown to be similar to the basal values found in conscious dogs acclimatized to the laboratory. The weak correlations found between basal plasma catecholamines and hemodynamic variables in all groups of conscious dogs reflect the complexity of factors interacting with the sympathetic nervous system in the maintenance of arterial pressure. These results document the variability that can be expected when using catecholamine levels as an index of sympathetic nervous system activity and the necessity of standardizing conditions for sample collection.

Interobserver variability in EEG interpretation.

A random sample of 100 active electroencephalographers in the United States evaluated 10-second samples of 12 selected EEGs. The evaluations consisted of multiple-choice questions related to the age of the patient, EEG finding, artifact, and consciousness of the patient. The rate of reporting the "correct" response was examined in terms of various respondent characteristics such as EEG board certification, age, percent of time in clinical EEG work, and number of recordings interpreted annually. This study indicates that, even today, there is considerable variability in EEG interpretation, and that this variability is influenced by specific reader characteristics.

Significance of positive cultures from donor left atrium and postpreservation fluid in heart transplantation.

BACKGROUND: The significance of positive perioperative cultures routinely obtained from the donor left atrium and postpreservation fluid during heart transplantation is unknown. METHODS: A retrospective chart review of 128 heart transplant recipients was done. RESULTS: A total of 106 of 128 patients had left atrial and/or postpreservation fluid cultures performed; 61 (57.5%) of them were positive. Forty-one positive left atrial or postpreservation cultures grew indolent organisms and 20 grew virulent organisms. Six donors had positive blood cultures, and five of the six did not have left atrial or postpreservation fluid cultures positive for the same organism. Seven recipients had positive blood cultures with organisms different from their corresponding left atrial or postpreservation fluid cultures. Three patients had sternal wound infections with organisms different from their donors' left atrial or postpreservation fluid cultures. Seven patients received additional antibiotics after heart transplantation specifically directed at a positive left atrial or postpreservation fluid culture for 5 to 7 days; none of them developed infection with these organisms. CONCLUSIONS: We found no evidence that positive donor left atrium or postpreservation fluid cultures increase the recipients' risk of infection. Nevertheless, we cannot refute that the small group of patients who received additional antibiotics might have developed an infection if they had not been treated. We recommend that the left atrial and postpreservation fluid cultures growing indolent organisms be discounted. However, if they grow more virulent organisms, consideration could be given to a brief course of specific therapy while awaiting recipient cultures.

A critical look at survival of diabetics with end-stage renal disease. Transplantation versus dialysis therapy.

The survival of 100 consecutive patients with diabetic nephropathy after treatment with hemodialysis, peritoneal dialysis, or renal transplantation was reviewed at our institution from 1976 to 1982. Standard actuarial survival analysis revealed an overall survival of 83% and 61% at one and two years, respectively. Coronary angiography was used as a screening procedure for renal transplantation. In the dialysis group, 27 patients were considered acceptable transplant candidates on the basis of the coronary angiography but were not transplanted for other reasons. When the survival analysis was limited to those "transplant candidates" the survival rates were 78%, 51%, and 8% at 1, 2, and 5 years, respectively. In comparison, survival after transplantation was 81%, 67%, and 45%, at 1, 2, and 5 years, respectively. In order to eliminate bias, survival comparisons were subsequently made using the Cox Proportional Hazard Model to take into account the time the transplant patients spent on dialysis prior to renal transplantation. When this analysis was performed, there was no significant difference in survival between transplantation and dialysis for the first two years, but overall survival after five years was significantly better after renal transplantation even when the comparison was limited to acceptable transplant candidates who remained on dialysis (P = .04). Survival for patients with significant coronary disease (greater than 70% stenosis of a coronary vessel or moderate to severe left ventricular dysfunction) was analyzed according to therapeutic modality. Although overall prognosis was poor in this group as a whole (1, 2, and 5 year survivals were 76%, 45%, and 19%, respectively), the cardiac patients had a trend to better survival after renal transplantation than when maintained on dialysis (P = .22). In addition to other factors such as quality of life, rehabilitation, and progression of other diabetic complications, the benefit of renal transplantation on patient survival must be considered when deciding between renal transplantation and maintenance dialysis therapy for diabetic patients with renal failure.

Detrimental effect of cyclosporine on initial function of cadaver renal allografts following extended preservation. Results of a randomized prospective study.

We report herein the results of a randomized prospective trial comparing maintenance cyclosporine (CsA)-prednisone immunosuppression to a regimen of azathioprine-prednisone-antilymphocyte globulin (ALG) in cadaver renal transplant recipients. Fifty-six patients were entered into this study with 31 assigned to the ALG group and 25 to the CsA group. These two groups were well matched for most major determinants of graft outcome and the mean renal preservation time was 37 hr in each group. The incidence of acute tubular necrosis (ATN) was high in both groups (58% ALG, 72% CsA, NS). There were five cases of primary nonfunction in the CsA group and only one in the ALG group (P = .05). Of the kidneys that functioned, the mean serum creatinine nadir (1.5 vs. 2.2 mg/dl, P = .06) and the mean number of days to reach the serum creatinine nadir (24.2 vs. 43.3 days, P = .03) were both less in the ALG group. The actuarial one-year graft survival rate in the ALG and CsA groups is 78% and 48%, respectively (P less than .05). This difference is mainly due to the large number of primary nonfunctioning grafts in the latter group, which we attribute to the effect of CsA's nephrotoxicity superimposed on renal ischemia incurred prior to transplantation. These data emphasize that, in order to realize the full benefit of CsA in cadaver transplantation, renewed emphasis must be placed on minimizing ischemic renal damage.

A multivariate analysis of risk factors for pneumonia following cardiac transplantation.

Fifty cardiac transplant recipients were followed over a 34-month period for evidence of pneumonia that developed in twelve patients. Potential risk factors evaluated fell into three categories: demographic (age, sex, race, and underlying cardiac disease); pretransplant status (hospitalized, intubated, pulmonary infiltrate, requirement for antibiotics, or the need for a ventricular assist device); and posttransplant therapy (amount and type of blood products, prolonged endotracheal intubation or reintubation, use of ventricular assist devices, immunosuppressive protocols, lymphocyte subset ratios, and occurrence of rejection, leukopenia, or CMV infection). The Cox proportional hazards model identified posttransplant reintubation (P = 0.009) and the use of protocols employing larger steroid dosages (P = 0.02) as significant risk factors for pneumonia. In a separate analysis, the occurrence of pneumonia was shown to be a significant risk factor for mortality (P = 0.018).

Should obese patients lose weight before receiving a kidney transplant?

BACKGROUND: The results of renal transplantation in obese recipients have been controversial, with some reports finding increased morbidity prohibitive and others finding increased morbidity acceptable. We attempted to determine whether obese patients in extreme excess of their ideal body weight should undergo transplantation. METHODS: The study population included 127 obese (body mass index >30 kg/m2) patients who were compared with a matched nonobese control group (body mass index <27 kg/m2) of 127 recipients with similar demographics. There were no significant differences between the groups according to donor source, recipient race or sex, retransplants, transplant percent reactive antibodies, cause of renal failure, or hypertension. However, significantly more obese patients had a pretransplant history of angina (11.2% vs. 3.2%, P=0.02) or a previous myocardial infarction (5.6% vs. 0.8%, P=0.04). RESULTS: The mean follow-up was 58.9+/-40 (range 3-170) months. Nonobese patients enjoyed a significantly (P=0.0002) greater patient survival (89% vs. 67%) at 5 years and suffered only about half the number of deaths (25 vs. 46) during the period of observation. Cardiac disease was the leading cause of death (39.1%) in the obese group. Patient death had a major impact on graft survival because there were no differences between the groups when death with graft function was censored from the analysis. There were no significant differences between the groups in delayed graft function, acute rejection, chronic rejection, length of hospital stay, operative blood loss, or mean serum creatinine up to 5 years. However, obese patients experienced significantly (P=0.0001) more complications per patient (3.3 vs. 2.2) and a greater incidence (P=0.0003) of posttransplant diabetes (12% vs. 2%). Similar cyclosporine blood levels were observed in obese recipients even though they were receiving 0.75-2 mg/kg/day less cyclosporine than the nonobese recipients. CONCLUSIONS: Outcome differences in obese renal transplant patients were primarily due to a higher mortality resulting from cardiac events. Obesity seems to have little effect on immunologic events, long-term graft function, or cyclosporine delivery. Aggressive pretransplant screening for ischemic heart disease is essential to identify an especially high-risk subgroup of obese patients. Although it would seem prudent to recommend weight reduction <30 kg/m2 to all patients before transplant, these data suggest that obese patients with a history of cardiac disease should not be transplanted until weight reduction has been accomplished.

Determinants of chronic renal allograft rejection in cyclosporine-treated recipients.

We analyzed the development of chronic rejection in 511 kidney-only renal transplants in 507 patients between July 1987 and November 1994. A database was established for recipients > or = 18 years old who received cyclosporine-based immunosuppression and demonstrated graft survival for a minimum of 12 months. The 347 recipients of cadaver transplants (67.9%) and 164 recipients of live donor transplants (32.1%) were followed for 12 to 102 months (mean 51 months). Chronic rejection was diagnosed in 124 transplants (24%), with a mean time to diagnosis of 23+/-18 months (range 3-92). Risk factors were identified in a multivariate analysis using the Cox model. The impact of the timing and severity of rejection episodes was analyzed in a univariate model. The presence of chronic rejection resulted in decreased (P=0.0001) 5-year graft survival for both cadaver graft (83.7% vs. 58.2%) and live donor graft (93.2% vs. 53.1%) recipients. Significant variables for the development of chronic rejection included an acute rejection episode (P=0.0001), a black recipient (P=0.0006), donor age > or = 50 years (P=0.006), and a serum creatinine level >2.0 mg/dl by 6 months after transplantation. Severity of rejection measured by peak serum creatinine or posttreatment return to baseline was not related to chronic rejection. However, acute rejection episodes lasting for more that 5 days (P=0.03) or occurring after 6 months (P=0.001) did influence time to chronic rejection. In addition, mismatching for donor-recipient race was a significant (P=0.008) risk factor for recipients of cadaver grafts. We conclude that acute rejection is the most significant risk factor for chronic rejection, and the long-term fate of grafts may be determined as early as the first 6 months. Racial matching of donor-recipient pairs may be useful to minimize chronic rejection risk. Future advances that diminish the incidence and severity of acute rejection may have the greatest impact on long-term survival.

The impact of routine mycophenolate mofetil drug monitoring on the treatment of cardiac allograft rejection.

INTRODUCTION: Mycophenolate mofetil (MMF) is a unique immunosupressive agent that has been shown to be efficacious in the treatment of cardiac allograft rejection. The utility of therapeutic drug monitoring on rejection prophylaxis and treatment is inconclusive. This study was undertaken to evaluate the incidence of rejection in relation to MMF trough level following heart transplantation. METHODS: Between May 1998 and February 1999, we retrospectively analyzed the clinical outcome of 215 heart transplant patients who had routine monitoring of MMF trough level at the time of scheduled endomyocardial biopsy. Patients were divided into three groups according to the time interval post transplant, and were evaluated in relation to the MMF trough level. Group I, 104 patients within 6 months of transplant; Group II, 90 patients, 6-12 months post transplant; and Group III, 71 patients beyond one year of transplant. Fifty patients had samples in more than one group. Rejection was defined as Grade > or = 3A based on ISHLT criteria. Mean follow-up period was 179+/-52 days. RESULTS: A significantly decreased incidence of rejection was noted in the samples with MMF trough level > or = mg/l compared to those with less than 2 mg/l inpatients evaluated within the first year of transplant (Group I: 8.8% vs. 14.9%, Group II: 4.2% vs. 11.3%, both P=0.05). In the presence of therapeutic cyclosporine (CSA) or tacrolimus (FK) blood levels, the incidence of rejection decreased significantly when MMF trough level was > or = 2 mg/l compared to samples with MMF trough level <2 mg/l (3.6% vs. 14.4%, P=0.005). No significant difference was noted in the presence of subtherapeutic CSA or FK levels (15.4% vs. 13.9%, P=NS). CONCLUSIONS: Monitoring of MMF trough levels may play a role in the management of cardiac transplant recipients during the first year post transplant.

High homocysteine, low folate, and low vitamin B6 concentrations: prevalent risk factors for vascular disease in heart transplant recipients.

BACKGROUND: A high plasma homocysteine concentration is a risk factor for atherosclerosis and thrombosis, which are major causes of morbidity and mortality in heart transplant patients. High homocysteine concentrations may be caused by lower folate and vitamin B6 levels. We hypothesized that these patients might have high homocysteine concentrations and low levels of folate and vitamin B6, which could contribute to the development of vascular complications. METHODS: Total fasting plasma homocysteine was measured in 189 cardiac transplant recipients and in healthy controls, as were concentrations of folate, vitamin B12, vitamin B6, and creatinine. RESULTS: Homocysteine concentrations were higher in recipients than controls (19.1+/-13.0 vs. 11.0+/-3.0 micromol/L, P<0.01), and hyperhomocysteinemia (>90th percentile for controls, 14.6 micromol/L) was seen in 68% of recipients (P<0.01). Folate and vitamin B6 concentrations were lower (5.9+/-4.2 vs. 7.9+/-4.2 pmol/L and 40+/-25 vs. 84+/-77 nmol/L, respectively; P<0.01 for both). Folate and vitamin B6 deficiencies were seen in 10.8% and 17.91% of recipients, respectively (P<0.01). Hyperhomocysteinemia was more frequent in patients with vascular complications after transplantation than in those without (79.2% vs. 63.8%, P<0.05). CONCLUSIONS: Elevated plasma homocysteine and deficiencies of folate and vitamin B6 are common in transplant recipients. A high homocysteine concentration was more common in patients with vascular complications. Prospective studies are now required to evaluate the role of these abnormalities as risk factors for the atherothrombotic complications of transplantation.

A randomized prospective controlled trial of oral acyclovir versus oral ganciclovir for cytomegalovirus prophylaxis in high-risk kidney transplant recipients.

BACKGROUND: Posttransplantation cytomegalovirus (CMV) infection remains a significant cause of morbidity in kidney transplant recipients. We performed a randomized prospective controlled trial of oral acyclovir versus oral ganciclovir for CMV prophylaxis in a group of renal allograft recipients considered at high risk for CMV disease due to the use of OKT3 induction therapy. METHODS: A total of 101 recipients of cadaveric (83) and zero haplotype-matched live donor (18) kidney transplants were entered into the trial. A total of 22 D-R- patients received no prophylaxis. Twenty-seven D+R-, 29 D+R+, and 23 D-R+ patients were randomized to receive 3 months of either oral acyclovir (800 mg q.i.d.) or oral ganciclovir (1000 mg t.i.d.). Doses were adjusted according to the level of renal function. The D+R- patients were also given CMV immune globulin biweekly for 16 weeks. Surveillance blood cultures were obtained at transplantation, at months 1, 2, 3, and 6, and when clinically indicated. The primary study end points were time to CMV infection and disease the first 6 months after transplantation. RESULTS: The mean follow up was 14.4 months. Both agents were well tolerated, and no drug interruptions for toxicity occurred. CMV was isolated in 14 of 39 (35.9%) acyclovir-treated and 1 of 40 (2.5%) ganciclovir-treated recipients by 6 months (P=0.0001). Symptomatic CMV disease occurred in 9 of 14 (64%) of the acyclovir patients, two with tissue-invasive disease. Infection rates for acyclovir vs. ganciclovir, respectively, stratified by CMV serology were: D+R-, 54 vs. 0%, P=0.0008; D+R+, 43 vs. 6.6%, P=0.01; D-R+, 8.3 vs. 0%, P=NS. No patient developed CMV infection while taking oral ganciclovir, however three delayed infections occurred 2-7 months after finishing therapy. Each patient had been previously treated for acute rejection. CONCLUSIONS: Oral acyclovir provides effective CMV prophylaxis only for recipients of seronegative donor kidneys. Oral ganciclovir is a superior agent providing effective CMV prophylaxis for recipients of seropositive donor kidneys. Recipients who are treated for acute rejection are at risk for delayed CMV infection during the first posttransplantation year.