Abstract: INTRODUCTION: Smoking is an important risk factor in any population group. According to previous studies, having been a smoker before heart transplantation (HT) confers a greater likelihood of developing any type of tumor or other complication after HT. Our objective was to determine the impact of having been a smoker before HT on survival, respiratory complications during the postoperative period, and long-term tumor development. MATERIALS AND METHODS: After excluding combined transplantations, pediatric transplantations, and retransplantations, we retrospectively reviewed 288 HT performed between November 1987 and September 2006. We divided patients into nonsmokers (including those who quit smoking more than 1 year before HT (n = 163), exsmokers for less than 1 year (n = 76), and those who smoked until HT (n = 49). The statistical tests were chi-square, Student t, analysis of variance (ANOVA), and Kaplan-Meier curves. RESULTS: There were more male patients among smokers and exsmokers than nonsmokers (93.9% vs 96.1% vs 82%, respectively; P = .003). There were no differences in baseline characteristics between the groups. Exsmokers remained intubated for a longer time than smokers or nonsmokers (33.4 +/- 44.6 vs 14.2 +/- 7.3 vs 17.9 +/- 19.2, respectively; P = .05). We observed the same trend in recovery unit stay (7.9 +/- 10.5 days vs 4.4 +/- 1.88 days vs 4.84 +/- 3.49 days, respectively; P = .021). The development of any type of tumor was also more frequent among smokers and exsmokers, although not significantly. The survival rate was similar in nonsmokers and exsmokers, although higher than in smokers (89.57 vs 92.11% vs 81.63%, respectively; P = .031). We did not observe differences in the causes of death. CONCLUSIONS: Patients who smoke or have smoked until shortly before HT showed a poorer prognosis and a longer recovery unit stay. There was also a trend to increased tumor development.
Abstract: INTRODUCTION: Many studies have shown a detrimental effect of female donor gender on heart transplantation (HT) outcome. OBJECTIVE: We retrospectively evaluated our experience in HT to determine the effect of donor gender on early survival. MATERIALS AND METHODS: We divided the sample of 464 primary HT from November 1997 to September 2006 into 4 groups: G1, female donor to a male recipient; G2, male donor to a male recipient; G3, male donor to female recipient; and G4, female donor to a female recipient. We performed a descriptive study of the baseline characteristics. The chi(2) test was used to determine differences in early mortality (30 days) between groups and a multivariate analysis to identify confounding factors to increase mortality. RESULTS: Although the univariate study showed that G1 showed a significantly lower early survival rate (84%) than G2 (91%), the multivariate study adjusted for donor and recipient weight and size, urgency level, previous surgery, and age only showed urgency level (odds ratio [OR] 2.6; 95% confidence interval [CI] 1.2-5.57; P = .016) and previous surgery (OR 5.8; 95% CI 2.7-12.4; P < .01) to be predictors of early mortality. When baseline characteristics were analyzed, we found that 31% of HT in G1 were urgent versus 18% in G2, and 32% of patients in G1 had previous surgery versus 17% in G2. CONCLUSIONS: Donor gender did not appear to negatively affect early survival. In our series, urgent HT in male recipients with a female was more frequent than with a male donor heart. The higher early mortality in male recipients of an urgent HT from a female than from a male donor was attributable to a higher baseline risk profile.
Abstract: INTRODUCTION: The present study evaluated the clinical and hemodynamic situation of patients with advanced heart failure considered for heart transplantation (HT) to examine the possible impact of prior cardiac disease. METHODS: We analyzed the pretransplant clinical, echocardiographic, and hemodynamic parameters of 422 consecutive HT patients. Pediatric and heart plus lung transplants were excluded, as were retransplantations. The results were compared by dividing the patients into three groups according to the background heart disease that led to HT: ischemic heart disease (IHD), dilated myocardiopathy (DMC), or valvular disease. RESULTS: Differences were observed in the baseline characteristics according to the type of heart disease. Male gender, hypertension, and diabetes were more frequent among IHD, while DMC patients tended to be younger. There were no differences in the clinical parameters such as liver and kidney function, in the functional class, or in the need for inotropic treatment over the days prior to transplantation. Likewise, no differences were recorded in the hemodynamic parameters, such as pulmonary pressure, pulmonary vascular resistance, or transpulmonary pressure gradient. As regards the echocardiographic parameters, the patients with DMC showed greater ventricular diameters and lesser ejection fractions for both ventricles. CONCLUSION: No important differences were recorded in the clinical situation or hemodynamic parameters of patients with advanced heart failure accepted for transplantation, according to the background cardiac disease. This observation could be due to the homogenization by strict transplant waiting list inclusion criteria.
Abstract: Research into hormone secretion by the heart and the release of such hormones in detectable amounts in response to given clinical conditions has provided new perspectives full of hopes but also uncertainties. These hormones, called natriuretic peptides, have diuretic, natriuretic and vasodilating properties. In heart failure, a relationship between ventricular dysfunction and the levels of these peptides, with implications for morbidity and mortality, has been demonstrated. Less research has been carried out into heart transplant, and while increased levels of hormones are also observed when graft dysfunction occurs, their role in acute rejection or as an independent factor associated with prognosis has not been clarified.
Abstract: BACKGROUND: Renal function deterioration is one of the main problems facing heart transplant recipients. The mammalian target of rapamycin (mTOR) inhibitors, in combination with or replacing calcineurin inhibitors, may help preserve renal function. The aim of this study was to evaluate the progression of renal function after switching the immunosuppressive regimen. PATIENTS AND METHODS: We studied 23 heart transplant recipients (5.5 +/- 4.5 years since transplantation). An mTOR inhibitor was introduced to replace cyclosporine (everolimus, 65%; sirolimus, 35%). Patient clinical characteristics and renal function were studied after switching. The statistical analysis used Student t test for paired data. RESULTS: The reason for the transplantation was ischemic cardiopathy (52%), dilated myocardiopathy (39%), or other causes (9%). Mean age at time of transplantation was 52 +/- 9 years. Comorbidities were as follows hypertension (43%), insulin-dependent diabetes (22%), hypercholesterolemia (39%), and ex-smokers (70%). The reason for the switch was increased creatinine (65%), appearance of tumors (26%), or others (8%). Previous creatinine level was 1.89 +/- 0.6 mg/dL with clearance of 61.7 +/- 23 mL/min and at the end of follow-up (mean follow-up, 11 +/- 6 months) creatinine level was 2.0 +/- 1.45 mg/dL with clearance of 68.3 +/- 35 mL/min, namely, no significant difference (P = .49 and P = .57, respectively). In the subgroup of patients who switched treatment due to renal dysfunction, initial creatinine level was 2.38 +/- 0.4 mg/dL with clearance of 42.3 +/- 10 mL/min and at the end of follow-up it was 2.28 +/- 0.2 mg/dL and 43.6 +/- 11 mL/min, respectively (P = .68 for creatinine and clearance). CONCLUSIONS: The introduction of mTOR inhibitors to the immunosuppressant regimen may be useful to delay renal functional deterioration caused by calcineurin inhibitors.
Abstract: INTRODUCTION: Preoperative pulmonary hypertension is an adverse prognostic factor for early morbidity-mortality after heart transplantation (HT). The persistence of hypertension is likewise associated with a poorer patient prognosis. The present study investigated the evolution of right cardiac pressures in the first year after HT with respect to the background cardiac disease. METHODS: This study of 60 consecutive patients subjected to HT analyzed the baseline clinical characteristics and mean right atrial and right ventricle systolic and diastolic pressures in a pre-HT study and during biopsies performed in the first 2 weeks as well as at 1, 3, 6, 9, and 12 months after transplantation. The study excluded retransplantations, heart and lung transplantations, and pediatric patients, as well as patients not subjected to biopsy because of early mortality. RESULTS: The mean patient age was 50 years (83% males); 31.7% were diabetics, and 33% showed hypertension. The background heart disease was of ischemic origin in 35% of cases, and consisted of dilated myocardiopathy in 33%, with a mean left ventricle ejection fraction (LVEF) of 23% and a mean pulmonary artery systolic pressure of 50.1 mm Hg. During the postoperative course, an important decrease versus baseline was observed in right heart pressures as soon as 2 weeks post-HT, with a drop in right ventricle (RV) systolic pressure from 50.3 +/- 13.7 to 42.5 +/- 10.4 mm Hg (P = .013), and a drop in RV diastolic pressure from 17.4 +/- 5.8 to 14.2 +/- 4.1 mm Hg (P = .007). This decreased tendency continued to a more moderate extent to the third month, after which the pressures stabilized. The same behavior was observed in patients with diseases of ischemic origin and in those with dilated myocardiopathy. CONCLUSIONS: In our series, right cardiac pressures showed an important decrease in the first days after HT, with stabilization by the third month-though without returning to normal values and without modifications in the first year after transplantation. No differences in this evolutive trend were seen according to the type of background heart disease.
Abstract: BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are relatively new drugs in the field of cardiac transplantation (HT), hence the need for further study of their secondary effects. We described the nature and incidence of secondary effects of these drugs in a group of HT recipients. PATIENTS AND METHODS: We studied 23 HT recipients aged 52 +/- 9 years (Male: 91%, body mass index: 27 +/- 3.7, ischemic cardiopathy: 52%, dilated cardiomyopathy: 39%) who were started on an mTOR inhibitor (everolimus: 65%, sirolimus: 35%) as part of their treatment. We have described the secondary effects detected during a follow-up period of 10.7 +/- 6 months. RESULTS: The reasons for starting the drug were renal impairment (65%), tumors (26%), and others (8%). During follow-up, 17% of patients required a dose reduction and 12% required drug withdrawal: edemas: 4%, recurrent infection: 4%, and hemolytic-uremic syndrome: 4%. Drug-attributable edemas presented in 26% of patients. Thirty nine percent suffered an infection that required hospital admission, 89% of which were lung and all bacterial two patients died due to the infection). The mean time to first infection was 5 +/- 6 months. In patients who had a treatment change due to tumors, 50% experienced improvement. We did not detect alterations in cholesterol, triglycerides, creatinine, or leukocytes. There was a nonsignificant trend toward decreased hemoglobin and platelet levels (P = .07 and P = .056, respectively). CONCLUSIONS: Lung infection was the principal complication among our patients treated with mTOR inhibitors. A large percentage required dose reduction (17%) and even drug withdrawal (12%) due to secondary effects.
Abstract: OBJECTIVE: The objective of this study was to compare baseline characteristics and long-term survival among patients undergoing heart transplantation (HT) according to the 3 main types of prior heart disease: ischemic, idiopathic dilated cardiomyopathy (IDC), and valvular. MATERIALS AND METHODS: Four hundred twenty-three HTs performed between 1989 and 2005 were included. We excluded pediatric transplantation, retransplantations, combined transplantations (lung and kidney), and transplantations due to heart diseases other than ischemic, IDC, and valvular. Baseline characteristics of the recipients were analyzed, as well as short-term and long- term survival by groups. Analysis of variance (ANOVA) was used for continuous variables and chi-square was used for categorical variables. Survival analysis was computed using Kaplan-Meier curves and the log-rank test, as well as multivariate analysis using logistic regression. RESULTS: The ischemic and valvular heart disease groups were older and had a more frequent history of prior heart surgery and circulatory support at the time of transplantation compared with the IDC group. The incidence of arterial hypertension and dyslipidemia was higher among ischemic heart disease recipients. Survival rates at 30 days did not show significant differences (ischemic, 88%; IDC, 93%; and valvular; 84%; P = .21). Long-term survival rates were greater in the IDC than in the valvular or ischemic heart disease groups (75% vs 65% and 62%, respectively; P = .021). The multivariate analysis showed an association between the IDC group and long-term survival (odds ratio [OR], 0.55; 95% confidence interval [CI] 0.35-0.89; P = .015). CONCLUSIONS: (1) Patients showed a different clinical profiles depending on their pretransplantation heart disease. (2) There were no differences in early mortality between the groups. (3) Long-term survival was significantly greater among IDC transplant recipients and similar in ischemic and valvular heart disease transplant recipients.
Abstract: OBJECTIVE: The objective of this study was to describe the clinical course of patients with chronic hepatitis C virus (HCV) infection undergoing heart transplantation (HT). MATERIALS AND METHODS: Among 499 patients transplanted in our hospital between January 1989 and September 2006, 11 subjects (2.2%) had chronic HCV infection. We analyzed liver function laboratory parameters pretransplantation as well as at 3, 6, 12 months, and last available, pre- and postsurgical hepatobiliary ultrasounds, and mortality. The mean time since HT was 32 +/- 23 months. RESULTS: No abnormalities in the liver parenchyma were observed on the ultrasound examinations performed before or after transplantation. There were 3 deaths (27%), none of which was related to HCV infection. Liver function laboratory parameters remained stable during the follow-up. CONCLUSIONS: The clinical course of patients with chronic HCV infection undergoing HT whose presurgical assessment did not show significant liver damage was favorable. No morphological or laboratory abnormalities were observed that would suggest reactivation of the infection during the follow-up.
Abstract: The 2006 International Society for Heart and Lung Transplantation registry reported that there were differences in mortality after heart-lung transplantation (HLT) depending on the etiology for transplantation. Our objective was to conduct an analysis on mortality after HLT at our center. MATERIALS AND METHODS: From January 1991 to December 2006, 25 HLT were performed on patients with the following characteristics: mean age of 38 +/- 11 years with 62% males and 4% with previous surgery. The cohort included 17% urgent transplants. The mean ischemia time was 198 +/- 60 minutes. We divided patients into four etiologic groups: congenital heart disease of the Eisenmenger type; primary pulmonary hypertension; chronic obstructive pulmonary disease/emphysema/fibrosis with right ventricular impact; or pulmonary dysfunction with concomitant left ventricular depression. Three patients were excluded from the analysis because they did not fit in any of the groups. RESULTS: The mean follow-up of the sample was 862 +/- 1290 days. The overall hospital survival as well as that at 1 and 5 years was 59%, 50%, and 37%, respectively. In the Eisemmenger's syndrome cohort no death occurred during hospitalization and survival at 5 years was 50%. CONCLUSIONS: HLT was a therapeutic option with high mortality. Hospital mortality was high in absolute terms. Congenital heart disease of the Eisenmenger type may be a lower risk group.
Abstract: The number of congenital heart disease (CHD) patients transplanted to date is small. The results are comparable to those undergoing heart transplantation (HT) for other etiologies. However, advances in pediatric surgery over recent years (eg, the Fontan procedure) has increased the demand for HT by a growing number of children who reach adulthood and who also have a different profile. We analyzed the clinical profile and survival of our CHD patients compared with other etiologies. MATERIALS AND METHODS: From July 17, 1991 to December 31, 2006, eight HT were performed in our center for CHD. A descriptive study determined the baseline characteristics and survival of these patients, compared with those of the overall transplant group and other subgroups (dilated cardiomyopathy, ischemic heart disease). RESULTS: Mean age was 26 years. Four (50%) CHD patients were diagnosed with single-ventricle anatomy, associated or not with other lesions; none had been operated with the Fontan procedure. Two patients died prematurely. Early, 1-, and 10-year survival was 75% at each time point. Early, 1-, and 10-year survival in the group with other diagnoses was 90%, 78%, and 60%, respectively, and in the dilated cardiomyopathy group it was 94%, 86%, and 72%, respectively. CONCLUSION: The current number of CHD transplant patients was small and young. The most common etiology was single-ventricle anatomy without a prior Fontan operation. Overall survival was comparable to HT for dilated cardiomyopathy.
Abstract: Dyslipidemia is a common problem among heart transplant (HT) recipients; it is a frequent risk factor in these patients that is exacerbated by immunosuppressive drugs. Statins are effective drugs to treat dyslipidemia in HT recipients, but control is suboptimal in some patients. Ezetimibe acts through inhibition of the enterohepatic recirculation, a mechanism different from but complementary to statins. Our objective was to assess the effect of the addition of ezetimibe to statin therapy among a population of HT patients. PATIENTS AND METHODS: We included 19 stable patients on statin therapy with suboptimal control of cholesterol. Determinations were performed at baseline on statins and at 6 months (statins + ezetimibe). The analyzed variables were total cholesterol and fractions, triglycerides, cyclosporine levels, CPK, SGOT/SGPT, and bilirubin. The statistics were Student's t test for paired samples. RESULTS: The overall mean age was 59 +/- 9 years with 95% males and mean BMI 27.5 +/- 3.5. The time since HT was 7 +/- 3 years. The reason for HT included ischemic heart disease in 68%. Pre-HT risk factors included in arterial hypertension in 32% and insulin-dependent diabetes mellitus in 10%, Dyslipidemia occurred in 68%; hypertriglyceridemia in 16% and hyperuricemia in 21%. Immunosuppression was cyclosporine in 100% and steroids in 94%. Type of lipid-lowering agent was simvastatin in 5%; pravastatin, 32%; atorvastatin, 58%; fibrates, 10%. The ezetimibe dose was 10 mg/day in 95% of cases. When ezetimibe was added we observed differences in total cholesterol values (total cholesterol at baseline: 279 +/- 74, total cholesterol with ezetimibe: 198 +/- 47 mg/dL; P = .0001) and LDL-cholesterol values (LDL-cholesterol at baseline: 171 +/- 69, LDL-cholesterol with ezetimibe: 109 +/- 41 mg/dL; P = .001). The remaining variables did not show significant differences. CONCLUSION: The addition of ezetimibe to statin therapy among heart transplant patients was effective to control dyslipidemia and showed an excellent safety profile.
Abstract: INTRODUCTION: Graft vessel disease (GVD) is one of the main long-term complications in heart transplant (HT) patients. At present, the diagnosis of this complication requires invasive procedures. Multislice CT is an emerging technique that allows visualization of the coronary anatomy, including the vascular lumen and wall thickness. Our objective was to establish the value of 16-detector multislice CT in the detection of GVD, compared with angiography and intravascular ultrasound (IVUS). PATIENTS AND METHODS: We studied 32 HT patients, who had a mean follow-up of 2016 days. CT was performed 24 hours prior to angiography, associated with IVUS if the latter proved normal. Comparisons were subsequently made using contingency tables to establish the sensitivity, specificity, and predictive values of the CT. RESULTS: Angiography was not performed on two patients, and eight were excluded from CT assessment due to serum creatinine values >1.5 mg/dL. Comparison of the CT findings with the invasive techniques yielded a sensitivity of 50%, a specificity of 81%, a negative predictive value of 81%, a positive predictive value of 50%, and a precision of 72%. CONCLUSIONS: Our results suggested good performance of the technique in screening for GVD because a high negative predictive value was recorded. We plan to increase the number of patients and use the 64-detector CT system to ensure greater time and spatial resolution.
Abstract: BACKGROUND: Cardiac allograft vasculopathy (CAV) is the leading cause of heart transplant failure after the first year. The etiological factors involved are currently a controversial matter. Intravascular ultrasound (IVUS) is considered the diagnostic procedure of choice. We assessed the relationship of cardiovascular risk factors with CAV. MATERIALS: We analyzed prospectively 22 patients. We conducted a first study with coronary angiography and IVUS at 36 +/- 3 days and a second at 598 +/- 49 days. We performed an average of 5.6 clinical revisions per patient, assessing the effect of the classic cardiovascular risk factors, the cause of heart failure, and the age of the patient and donor. The statistics used were chi(2), Fisher exact test, and Student t test. RESULTS: CAV was found in 10 subjects (45.5%). Univariate analysis showed statistically significant differences in the assessment of the presence of diabetes and dyslipidemia posttransplantation, but not pretransplantation. Among the patients with CAV there was a higher percentage of diabetics (32.8% vs 12%, P < .01). The patients with CAV also had higher levels of total cholesterol (211 +/- 40 mg/dL vs 195 +/- 35 mg/dL, P = .02), triglycerides (172 +/- 108 mg/dL vs 136 +/- 66 mg/dL, P = .03), low-density lipoprotein (133 +/- 35 mg/dL vs 117 +/- 30 mg/dL, P = .01), and lower high-density lipoprotein levels (46 +/- 15 mg/dL vs 52 +/- 12 mg/dL, P = .03). CONCLUSIONS: Only the diabetes and dyslipidemia present in the posttransplantation period were associated with CAV, which highlights the fact that it is a condition that both shares and has different features with atherosclerosis and probably requires a different diagnostic-therapeutic approach.
Abstract: INTRODUCTION AND OBJECTIVES. At present, there is some controversy about the impact of diabetes mellitus on heart transplant patients. The effect of the disease on mortality and on other complications, such as infection or rejection, is unclear. The objective of this study was to investigate these factors in our heart transplant patients. METHODS. We studied 365 consecutive patients who underwent heart transplantation between November 1987 and May 2003. We divided them in three groups according to whether they had pretransplantation diabetes (group 1), de novo diabetes (group 2), or no diabetes (group 3). Baseline variables and the development of complications were recorded, and findings were analyzed using Student's t test, chi squared test, and Kaplan-Meier survival analysis. RESULTS. There was no difference in the 1-year or 5-year survival rate between the groups (P=.24 and P=.32, respectively). Patients with pretransplantation and de novo diabetes were older (54.6 years vs 54.9 years vs 50.6 years, P=.04), had a higher prevalence of hypertension (48% vs 36% vs 23%, P=.001), and had more frequently been treated with tacrolimus (10% vs 12% vs 4%, P=.04) or steroids (92% vs 86% vs 70%, P=.001). The incidence of rejection during follow-up was greater in these two groups (64% vs 70% vs 45%, P=.001). CONCLUSIONS. Neither pretransplantation diabetes nor de novo diabetes had a negative impact on survival in our heart transplant patients. The disease's presence was associated with treatment with steroids and tacrolimus. In these patients it would be preferable to individualize immunosuppressive therapy.
Abstract: OBJECTIVE: To evaluate the frequency of infection according to the immunosuppressive regimens used in our center. MATERIALS AND METHODS: From 259 consecutive heart transplants we excluded pediatric cases, retransplants, combined transplants (lung and kidney) and immunosuppressive regimens with fewer than 10 cases. The six groups analyzed were: (1) OKT3 (7 days) + cyclosporine (CsA) + mycophenolate mofetil (MMF) + steroids (S); (2) OKT3 (7 days) + CsA + azathioprine (AZA) + S; (3) OKT3 (10 days) + CsA + MMF + S; (4) OKT3 (10 days) + CsA + AZA + S; (5) interleukin-2 (IL-2) antagonists + CsA + MMF + S; (6) IL-2 antagonists + tacrolimus + MMF + S. Infection was considered significant when it causal hospital admission or prolonged hospitalization. RESULTS: With a total mean follow-up of 54 +/- 43 months, the total percentage of infection-free patients at the end of follow-up was 45.5%. Infection-free survival was lower among patients administered induction with OKT3 antibodies for 10 days, combined with cyclosporine, either with MMF (10%, group 3) or with azathioprine (27%, group 4), compared to those given IL-2 antagonists (particularly in combination with tacrolimus and MMF-69.2%, group 6). CONCLUSIONS: The results of this study showed that infection was frequent in heart transplantation. Furthermore, induction therapy with OKT3 monoclonal antibodies was associated with an important number of infections (particularly viral infections). Comparison of the treatment groups showed that the regimen associated with fever infections included an IL-2 receptor antagonist with tacrolimus, MMF, and S.
Abstract: Patients with a heart transplant (HT) may require changes in their immunosuppressive maintenance medication. The basic treatment regimen in our patients consisted of an anticalcineurin agent, an antimetabolite, and a steroid. OBJECTIVE: We undertook a descriptive study to quantify the incidence and causes of these changes and determine how they occur. MATERIALS AND METHODS: We included the 432 HT performed at our center from November 1987 to October 2005. The baseline treatment was considered to be the treatment given following HT, and the maintenance treatment was that taken at the time of data collection. Kaplan-Meier survival curves were constructed for the analysis. RESULTS: The most significant change was the switch from azathioprine to mycophenolate mofetil. The survival rate after 17 years was 66%. CONCLUSIONS: As in the international registries, there has been an evident reduction in the use of cyclosporine and more particularly of azathioprine, in favor of tacrolimus and mycophenolate mofetil, respectively. No changes in the use of steroids have been observed. These data reflect an increasingly greater use of immunosuppressive agents with reduced side effect profiles.
Abstract: Since their introduction onto the market, interleukin-2 antagonists have been increasingly used by a growing number of transplant units. Their benefits versus OKT3 appear evident, although the optimal dose remains to be established. Our objective was to establish possible differences related to the use of two versus five doses of daclizumab. MATERIALS AND METHODS: This study evaluated 81 consecutive patients treated with two bolus doses of daclizumab (1 mg/kg) on days 1 and 14 posttransplantation. We excluded retransplantations, pediatric transplantations, and combined transplantations. We compared our series to a previous trial involving the administration of a single bolus dose every 14 days (five boluses in total). Study variables included the number of graft rejections, the number of infections, and the mortality. Statistical analysis was performed using the chi square and Student's t tests. Significance was set at P < .05. RESULTS: There were no differences between groups in the baseline characteristics of the patients. The number of rejection episodes during the first year was significantly lower among the patients in our series treated with two bolus doses of daclizumab than in the series of patients treated with five bolus doses: 24 (30%) vs 17 (61%) episodes (P = .003). No significant differences were observed for mortality: the group receiving two boluses registered 10 deaths (12%) versus two (7%) in the group receiving five boluses (P = .4), or infection rate: 11 patients (40%) in the group receiving five bolus versus 31 patients (38%) in the group given two bolus doses (P = .9). CONCLUSIONS: Our results suggested that induction therapy with two doses of daclizumab was at least as effective in preventing rejection as five doses, with no negative effects on patient survival.
Abstract: OBJECTIVE: To perform an analysis comparing long-term survival in heart transplant (HT) patients depending on the immunosuppressive regimen. MATERIALS AND METHODS: The study included 317 consecutive HT patients. We excluded pediatric cases, retransplants, combined transplants (lung and kidney), and immunosuppressive regimens with fewer than 10 cases. The six groups analyzed were: (1) OKT3 7 days + cyclosporine (CsA) + mycophenolate mofetil (MMF) + steroids (S); (2) OKT3 7 days + CsA + azathioprine (AZA) + S; (3) OKT3 10 days + CsA + MMF + S; (4) OKT3 10 days + CsA + AZA + S; (5) interleukin-2 (IL-2) antagonists + CsA + MMF + S; and (6) IL-2 antagonists + tacrolimus + MMF + S. Probability of survival was analyzed by Kaplan-Meier and log-rank methods. RESULTS: The groups were heterogeneous regarding the number of patients and follow-up. The baseline characteristics were similar, although there were differences in surgery times. The survivals by groups at the end of the follow-up period were: group 1: 75.8%; group 2: 51.2%; group 3: 63.6%; group 4: 25.3%; group 5: 91.2%; and group 6: 84.6%. A major reduction in survival was observed in the groups that were given induction with OKT3 monoclonal antibodies (groups 1, 2, 3, and 4), particularly when AZA was combined in the maintenance phase (groups 2 and 4) and when the induction dose was high (10-day therapy in groups 3 and 4). CONCLUSIONS: Our study suggested an association between the immunosuppressive regimen and the long-term survival of HT patients. The best results were obtained with an induction regimen based on IL-2 antagonists. On the basis of the survivals observed in this study, the maintenance combination we regard as "optimal" at this time is based on a combination of CsA, MMF, and steroids.
Abstract: The use of amiodarone before transplantation has been linked to an increased number of complications, acute graft failures, and early mortality after a heart graft. We undertook a retrospective, descriptive, case-controlled study involving early mortality and acute graft failure. The 396 consecutive patients included 25 subjects who had been prescribed amiodarone for at least 30 days before transplantation. We excluded retransplantations, pediatric transplantations, and combined transplantations. The endpoints were early mortality and acute graft failure. No significant differences were observed in early mortality and acute graft failures. The multivariate analysis did not reveal any variable that correlated with early mortality. Our study did not support the idea that amiodarone constituted a negative predictor of early survival or acute graft failure.
Abstract: INTRODUCTION: It is known that there is a high incidence of diabetes mellitus (DM) among heart transplant (HT) patients, which may be up to 30% at 5 years. The presence of DM has been associated with increased morbidity (infections, renal dysfunction, or graft vascular disease), and its development has been related primarily to immunosuppressive therapy. The objective of this study was to determine, in our experience, the presence of predictive variables for the development of DM following HT. METHODS: We studied 315 consecutive non-DM patients (88.6% men, mean age 51.5 years) who underwent HT in our hospital from November 1987 to May 2003, analyzing all variables that could be related to the development of DM during follow-up. Student t-test and chi(2) test were used for univariate statistical analysis and logistic regression for multivariate analysis. RESULTS: Of the 315 patients, 64 developed DM (20.3%) during a mean follow-up of 3.3 years. The univariate analysis showed that patients developing DM are older (54.9 +/- 8.7 versus 50.7 +/- 11.8 years, P = .008), have a higher body mass index (BMI) (27.3 +/- 3.8 versus 25.7 +/- 3.7, P = .003), a higher prevalence of HT (37.5% versus 23.5%, P = .023), a lower frequency of urgent HT (9.4% versus 26.2%, P = .004), are more often treated with steroids (85.9% versus 70.1%, P = .011) and tacrolimus (12.5% versus 4.4%, P = .015), and have a higher frequency of rejection episodes (71.2% versus 44.6%, P = .001). Multivariate analysis identified the following as predictive factors for the development of DM: age (OR = 1.04, P = .013), urgent HT (OR = 0.36, P = .031), treatment with tacrolimus (OR = 3.89, P = .012), and number of rejections (OR = 2.34, P = .002). CONCLUSION: In our population, age, urgent HT (which had a protective effect), treatment with tacrolimus, and number of rejections were independent predictive variables for the development of DM during follow-up.
Abstract: BACKGROUND AND AIMS: Immunosuppressive therapy has undergone great changes in recent years as a result of the introduction of new drugs, presumed a prior to be more effective and better tolerated. The greatest advance seems to have been the introduction of interleukin-2 (IL-2) receptor antagonists. The objective of this study was to determine whether the use of IL-2 receptor antagonists in induction therapy has implications for the development of rejection and survival. MATERIALS AND METHODS: Three hundred sixty-five consecutive cardiac transplant patients who received induction therapy were included. Heart-lung and transplants in children under 10 years were excluded. Three groups were compared according to the induction therapy (OKT3, 10 days; OKT3, 7 days; and IL-2R antagonists). Each treatment corresponded to a time period: OKT3 10 days from June 1989 to April 1994; OKT3 7 days from May 1994 to October 2002; and IL-2R antagonists from November 2002 to May 2004. Baseline characteristics of recipient and donor, surgical times, postsurgical complications, maintenance immunosuppression, number of rejections, time (days) to first rejection, and probability of survival at 1 year were recorded. We used analysis of variance, chi(2) test, Kaplan-Meier curves, and log-rank test as appropriate. A P-value < .05 was considered significant. RESULTS: There were significant differences in the characteristics of the transplanted patients in the various time periods. Thus, recipients in the OKT3 10 day group had worse status but better donors, whereas recipients in the IL-2R antagonists group had better status but older donors with longer duration of ischemia. The incidence of acute graft failure was similar in the three groups. The number of rejection episodes in the first year was higher among the OKT3 groups (OKT3 10 days, 1.7 +/- 1.3; OKT3 7 days, 1.2 +/- 1.2; IL-2R antagonists, 1.0 +/- 1.2; P = .02) and the probability of survival at 1 year was also lower (OKT3 10 days, 74%; OKT3 7 days, 77%; IL-2R antagonists, 94%; P = .0007). CONCLUSIONS: Induction therapy with IL-2 antagonists offers important advantages over treatment with OKT3 in terms of survival, with absolute and relative risk reductions of 20% and 27%. Furthermore, it did not increase the number of rejections, although this may have been due to the greater use of MMF versus azathioprine.
