De novo immunosuppression with sirolimus and tacrolimus in heart transplant recipients compared with cyclosporine and mycophenolate mofetil: a one-year follow-up analysis.

BACKGROUND: Limited data exist regarding the safety and efficacy of sirolimus in combination with a calcineurin inhibitor in heart transplant recipients. METHODS: From January 2001 to June 2002, 31 de novo heart transplant recipients (treatment group) received a combination of sirolimus, tacrolimus, low-dose rabbit antithymocyte globulin, and glucocorticoids. Outcomes, such as actuarial survival, rate of rejection, incidence of infection, probability of developing diabetes mellitus, renal function, platelet and white blood cell counts, and incidence of coronary artery disease at 1 year, were compared with a cohort of 25 patients (control group) who underwent transplantation primarily in 2000 and in early 2002 treated with cyclosporine, mycophenolate mofetil, and glucocorticoids. All patients were followed up for at least 12 months. RESULTS: Kaplan-Meier actuarial 1-year survival rates were equivalent between groups (97% for the treatment group and 88% for the control group), as was freedom from allograft rejection (48% and 42% for treatment and control groups, respectively). No cases of transplant arteriopathy were noted within the first posttransplantation year. Renal function was not significantly affected in either group. There was a striking increased incidence of mediastinitis in the treatment group (19%) versus 0% in the control group (P = .02). Tacrolimus-sirolimus therapy was associated with a nearly 11-fold increased incidence of new-onset diabetes mellitus as well (P = .004). CONCLUSION: Tacrolimus, sirolimus, and steroids (following low-dose rabbit antithymocyte globulin) were associated with an increased incidence of mediastinitis and posttransplantation diabetes mellitus. No obvious long-term benefit on survival, arteriopathy, or renal function was noted.

The role of gender in heart transplantation.

BACKGROUND: The effect of donor and recipient gender on the outcome of heart transplantation (HT) remains uncertain. METHODS: One hundred seventy-four patients who underwent HT were divided into four groups according to donor and recipient gender. Group A consisted of 81 men who received male donor hearts, group B of 18 women who received female donor hearts, group C of 21 women who received male donor hearts, and group D of 54 men who received female donor hearts. All patients were treated by the same group of surgeons according to standard HT protocols. Comparisons were made between groups with regard to short- and long-term outcomes. RESULTS: Donor gender and recipient gender did not affect outcomes significantly. Overall, donor-recipient gender mismatching significantly increased the number of rejection episodes and reduced creatinine clearance, survival, and censored survival in the first year after HT (p < 0.05). More specifically, among female recipients, donor-recipient gender mismatching significantly increased the number of rejection episodes and decreased creatinine clearance in the first year after HT (p < 0.05); among male recipients, donor-recipient gender mismatching significantly reduced 1-year survival and censored survival to date after HT (p < 0.05). CONCLUSIONS: Donor-recipient gender matching plays a significant role in determining HT outcomes.

Management of left ventricular assist device infection with heart transplantation.

BACKGROUND: Left ventricular assist devices (LVADs) are being used as bridges to heart transplantation (HT). Infection of the LVAD in this patient population represents a serious complication, as simple LVAD removal or delaying HT may result in death. To improve outcomes in this group of patients, we performed HT in the presence of LVAD infection. METHODS: Eighteen patients underwent LVAD implantation followed by HT. Ten underwent HT in the absence of LVAD infection (group 1); and 8, in the presence of LVAD infection (group 2). All patients were treated similarly except for modification of immunosuppression in group 2 patients. RESULTS: Infectious and noninfectious complications were equivalent between the two groups. There was no difference between groups in regard to intraoperative deaths (one versus none), long-term survival (8/10 versus 7/8), wound complications (three versus none), and mean length of hospital stay after HT (21 versus 26 days). CONCLUSIONS: Patients with LVAD infection are too seriously ill to allow LVAD removal or delay of HT. Transplantation in the face of infection is an effective treatment option.

The usefulness of diagnostic tests on pericardial fluid.

STUDY OBJECTIVES: To determine the physical, chemical, and cellular characteristics of pericardial fluid in various disease states and to assess their diagnostic accuracies. SETTING: A metropolitan university hospital. DESIGN: Consecutive case series. PATIENTS: One hundred seventy-five hospital patients, aged 1 month to 87 years, who had undergone pericardiocentesis (n = 165) or control subjects who had undergone open heart surgery (n = 10) between 1984 and 1996. MEASUREMENTS: The appearance of pericardial fluid and results of chemistry tests, cell counts, cytologic studies, Gram's stain, and microbial cultures were obtained by chart review. The etiology of each pericardial fluid sample was determined using prospective diagnostic criteria. RESULTS: Exudates differed from transudates by higher leukocyte counts and ratios of fluid to serum lactate dehydrogenase levels. Fluid glucose levels were significantly less in exudates. Sensitivity for detecting exudates was high for specific gravity > 1.015 (90%), fluid total protein > 3.0 g/dL (97%), fluid to serum protein ratio > 0.5 (96%), fluid lactate dehydrogenase ratio > 0.6 (94%), and fluid to serum glucose ratio < 1.0 (85%). None of these indicators were specific. Fluid total protein and specific gravity were moderately correlated (r = 0.56). Fluid cytologic study had a sensitivity of 92% and specificity of 100% for malignant effusion. No other test was diagnostic for a specific etiology. Among infection-associated effusions, culture-positive fluid had more neutrophils, higher lactate dehydrogenase levels, and lower ratios of fluid to serum glucose than culture-negative (parainfective) fluid. CONCLUSIONS: Evaluation of pericardial fluid might be limited to cell count, glucose, protein, and lactate dehydrogenase determinations plus bacterial culture and cytology. While not used routinely, other tests that may be highly specific for particular diseases should be ordered only to confirm a high clinical suspicion.

Standard criteria for an acceptable donor heart are restricting heart transplantation.

BACKGROUND: The lack of satisfactory donor organs limits heart transplantation. The purpose of this study was to determine whether the criteria for suitability of donors may be safely expanded. METHODS: One hundred ninety-six heart transplantations were performed on 192 patients at our institution from January 1992 to 1995 and were divided into two groups. Group A donors (n = 113) conformed to the standard criteria. Group B donors (n = 83) deviated by at least one factor and consisted of the following: 16 hearts from donors greater than 50 years of age, 33 with myocardial dysfunction (echocardiographic ejection fraction = 0.35 +/- 0.10, dopamine level exceeding 20 micrograms.kg-1.min-1, and resuscitation with triiodothyronine), 33 undersized donors with donor to recipient weight ratios of 0.45 +/- 0.04, 48 with extended ischemic times of 297.4 +/- 53.6 minutes, 25 with positive blood cultures, 16 with positive hepatitis C antibody titers, and 7 with conduction abnormalities (Wolff-Parkinson-White syndrome, prolonged QT interval, bifascicular block). RESULTS: Thirty-day mortality was 6.2% (7/113) in group A and 6.0% (5/83) in group B. Mortality in group A was attributed to 3 patients with myocardial dysfunction, 2 with infection, 1 with acute rejection, and 1 with pancreatitis; group B had 2 with myocardial dysfunction, 1 with infection, 1 with aspiration, and 1 with bowel infarction. At 12 months, survival and hemodynamic indices were similar between the groups. Of the 16 recipients with hepatitis C-positive hearts, 5 have become hepatitis C positive with mild hepatitis (follow up, 6 to 30 months). CONCLUSIONS: Expanding the criteria for suitability of donor hearts dramatically increases the number of transplantations without compromising recipient outcome.

Defining the role of aprotinin in heart transplantation.

BACKGROUND: Heart transplantation is associated with excessive bleeding due to recipient coagulopathy, frequent need for reoperative median sternotomy, and prolonged cardiopulmonary bypass. Aprotinin reduces bleeding and the inflammatory response after cardiopulmonary bypass, but there are concerns about efficacy and side effects. METHODS: To determine the role of aprotinin in primary and reoperative sternotomy heart transplantation, we studied 70 patients undergoing heart transplantation between August 1993 and October 1994. Thirty-eight undergoing primary sternotomy for heart transplantation and receiving no aprotinin were randomized to group A (n = 20); patients in group B (n = 18) received the full recommended dose. Similarly, 32 patients undergoing reoperative heart transplantation were randomized to group C (n = 16), receiving no aprotinin, and to group D (n = 16), receiving aprotinin at the full recommended dose. All patients received the same immunosuppression regimen. Similarities in the groups included recipient age, weight, preoperative hemodynamic indices, creatinine, creatinine clearance, platelet count, hemoglobin, percentage receiving warfarin, prothrombin time, partial thromboplastin time, cardiopulmonary bypass time, and creatinine level at 48 hours. RESULTS: There were no significant differences postoperatively between groups A and B. Differences (p < 0.05) 24 hours postoperatively between groups C and D, respectively, included: total blood product requirement (5.9 +/- 3.8 versus 3.6 +/- 2.0 U), total fluid balance (+752 +/- 300 versus -250 +/- 185 mL), chest tube drainage (894 +/- 120 versus 526 +/- 95 mL), alveolar-arterial O2 difference (120.4 +/- 45.9 versus 95.5 +/- 33.5), and pulmonary artery mean pressures (28.2 +/- 4.6 versus 21.1 +/- 3.5 mm Hg). CONCLUSIONS: Aprotinin decreases bleeding after reoperative heart transplantation without renal dysfunction. Decreased inflammation is manifested as reduced fluid requirement and improved pulmonary and right heart function, which benefit patients during the posttransplantation period. Aprotinin at recommended doses is effective and safe for patients undergoing reoperative heart transplantation.

Repair of coarctation of the aorta in adults: the fate of systolic hypertension.

BACKGROUND: The benefit of coarctation repair in adults has been questioned by suggesting that hypertension may not be relieved by the operation and that surgical intervention may have no impact on the natural history of the disease. METHODS: To delineate the impact of surgical intervention on systolic hypertension, we conducted a retrospective review of 26 adults with a mean age of 32 +/- 10 years who underwent coarctation repair between 1987 and 1993. All patients were hypertensive (mean systolic blood pressure, 174 +/- 21 mm Hg; range, 140 to 220 mm Hg), and 18 patients (69%) were on a regimen of at least one hypertensive medication at the time of surgical admission. All patients underwent catheterization, and the mean peak systolic gradient across the coarctation was 61 +/- 25 mm Hg (range, 25 to 120 mm Hg). Operation included resection and end-to-end anastomosis (3 patients), resection with an interposition tube graft (6 patients), a bypass graft (11 patients), and patch angioplasty (6 patients). There was no hospital mortality or late morbidity. RESULTS: Intermediate follow-up was available at a mean of 2.3 +/- 2 years (range, 1 to 7 years). At last follow-up, the peak systolic gradient between the upper and lower body was trivial (< or = 10 mm Hg) in 23 patients (88%) and mild (11 to 20 mm Hg) in 3 (12%). All patients had significant improvement in systolic blood pressure (p < 0.001) compared to preoperative values, and the majority (23, 88%) were normotensive. More than half of the patients (14, 54%) were still on a regimen of antihypertensive medication at last follow-up, with a trend (p = 0.06) toward older patients requiring medication. CONCLUSIONS: Surgical repair of coarctation in adults is an effective, low-risk procedure, which results in a significant improvement in systolic hypertension and a decreased requirement of antihypertensive medications.

Safe application of diagnostic laparoscopy during biventricular assistance.

We performed diagnostic laparoscopy in a patient who was critically unstable while on an ABIOMED BVS 5000 biventricular assist system. A relatively unique feature of the ABIOMED is the venous return being dependent only on gravity and the drawing force of venous return being the height of the inflow cannula compared with the level of the ABIOMED blood pump assembly; this did not preclude the use of pneumoperitoneum necessary for laparoscopy. The safe application of diagnostic laparoscopy in patients on a ventricular assist device is of importance in an era of increasing use of these devices and the increased potential for intraabdominal complications in this population.

Membrane phospholipid asymmetry as a factor in erythrocyte-endothelial cell interactions.

The tendency of human erythrocytes to adhere to vascular endothelial cells was assessed as a function of the transbilayer distribution of the phospholipids of the erythrocyte membrane, using erythrocyte ghosts in which transbilayer lipid arrangement was manipulated by varying the conditions under which the ghosts were prepared. By two different assays, ghosts with symmetric lipid bilayers adhered strongly to monolayers of cultured endothelial cells, whereas ghosts with normal asymmetric membranes, like normal erythrocytes, did not. These results provide direct evidence that changes in phospholipid asymmetry can alter the tendency of erythrocytes to adhere to endothelial cells, and therefore imply that transbilayer phospholipid arrangement may influence the behavior of erythrocytes in the circulatory system and may contribute to the formation of microvascular occlusions.