Current Situation and Prognostic Evolution of Combined Heart-lung Transplantation in a European Union Country.

Background: This study aims to evaluate the entire experience in heart-lung transplantation (HLTx) in a country of the European Union with 47 million inhabitants according to the etiologies that motivated the procedure. Methods: A retrospective study on 1,751 consecutive transplants (HLTx: 78) was performed from 1990 to 2020 in two centers. Overall survival, adjusted for clinical profile and etiological subgroups, was compared. 7 subgroups were considered: 1) Cardiomyopathy with pulmonary hypertension (CM + PH). 2) Eisenmenger syndrome. 3) Congenital heart disease (CHD). 4) Idiopathic pulmonary arterial hypertension (IPAH). 5) Cystic fibrosis. 6) Chronic obstructive pulmonary disease (COPD)/Emphysema. 7) Diffuse interstitial lung disease (ILD). Results: Early mortality was 44% and that of the rest of the follow-up was 31%. There were differences between HTLx and HTx in survival, also comparing groups with a similar clinical profile with propensity score (p= 0.04). Median survival was low in CM + PH (18 days), ILD (29 days) and CHD (114 days), intermediate in Eisenmenger syndrome (600 days), and longer in IPAH, COPD/Emphysema and cystic fibrosis. Conclusion: HLTx has a high mortality. The etiological analysis is of the utmost interest to make the most of the organs and improve survival.

Molecular Alterations of Nucleocytoplasmic Transport in Patients on the Heart Transplantation Waiting List and Its Correlation With the Severity and Etiology of Heart Failure.

OBJECTIVES: To evaluate whether the levels of some molecules implicated in nucleocytoplasmic transport in human cardiomyocytes are related to the severity of heart failure (HF) in patients on the heart transplantation (HT) waiting list, and to determine whether there is a differential pattern of molecular alteration between ischemic cardiomyopathy (ICM) and non-ischemic dilated cardiomyopathy (DCM). METHODS: Sixty-three blood samples collected before HT were analyzed to identify the levels of IMPORTIN5 (IMP5); IMPORTINalpha2; ATPaseCaTransp (ATPCa); NUCLEOPORIN153kDa (Nup153); NUCLEOPORIN160kDa (Nup160); RANGTPaseAP1 (RanGAP1) and EXPORTIN4 (EXP4). These data were then compared between patients with advanced HF with or without the need for ventricular support with extracorporeal membrane oxygenation (ECMO) as a bridge for HT, as well as between patients with non-ischemic DCM and patients with ICM. RESULTS: Thirty-three patients had ICM, 26 had non-ischemic DCM, and 4 had heart disease. Seventeen patients required ventricular assistance as a bridge to HT. The levels of ATPCa, RanGAP1, and IMP5 were significantly higher in patients with ECMO, while EXP4 was significantly higher in patients without ECMO. Patients with DCM showed higher levels of IMP5, RanGAP1, and Nup153 than those with ICM. CONCLUSION: Patients with advanced HF in critical condition (with ECMO as a bridge for HT) presented with significantly higher levels of ATPCa, RanGAP1, and IMP5, while patients with DCM had significantly higher levels of RanGAP1, IMP5, and Nup153. It remains to be clarified whether the determination of these molecules would facilitate the early identification of this group or if their alteration occurs as consequence of circulatory support with ECMO.

Idarucizumab in High-risk Thoracic Surgery.

Direct oral anticoagulants have suggested a favorable profile compared with vitamin K antagonists. However, the lack of treatment to reverse the effect of direct oral anticoagulants has limited its use in some patients who require rapid reversal of anticoagulation, as those included in the transplant waiting list. Idarucizumab is a recently approved drug to reverse the anticoagulant effect of dabigatran. However, the clinical experience when using this drug is scarce. Herein, we present a clinical case on anticoagulation reversal with idarucizumab to perform heart and lung transplantation in a patient with Eisenmenger syndrome.

Incidence of development of obesity after heart transplantation according to the calcineurin inhibitor.

BACKGROUND: Development of obesity after heart transplantation (HT) is a common complication, largely attributed to immunosuppressive therapy. The objective of this study is to compare the incidence of development of obesity after HT, according to the calcineurin inhibitor (CNI) used (cyclosporine [CsA] vs tacrolimus [Tac]). METHODS: We studied 101 consecutive HT patients from November 2006 to December 2010. A diagnosis of overweight-obesity was made by a body mass index of ≥25 kg/m(2), which was assessed before HT and at 1 year after HT. Patients were randomly assigned to the administration of CsA or Tac by a simple randomization method using a computer program (56% received CsA and 44% Tac). RESULTS: Of the 101 patients, 77% were men, and ischemic heart disease was the most common indication for HT. At baseline, there were no differences in weight between groups treated with CsA or Tac. The mean weight for each group was 71.5 ± 12 and 75 ± 14 kg, respectively (P = .2). The weight increase was greater among CsA patients: after HT, the weight gain was 6.9 ± 11 kg in the CsA group, whereas a minimal weight loss of 0.03 ± 14 kg (P = .008) was experienced in the group treated with Tac. The multivariate analysis showed that only CsA treatment was an independent predictor of development of obesity 1 year after HT (odds ratio, 3.84; 95% CI, 1.04-14.21; P = .01). CONCLUSION: Weight gain after HT may be related to the CNI used and CsA seems to be the CNI that produces the greatest increase.

Is age a limiting factor for access to transplantation?

As a result of increased life expectancy and quality of life, there is an increasing number of patients older than 65 years of age who require the possibility of heart transplantation (HTx). Traditionally, recipient age older than 65 years has been considered a contraindication for performing a HTx because these patients have more comorbidities, are more affected by the adverse effects of immunosuppressive drugs, and obtain a smaller benefit in the medium and long term. Therefore, given the shortage of donors, priority was given to younger recipients. In recent years, studies have been published demonstrating that HTx in this population segment is possible. These results indicate that despite suffering more infections and having longer hospital stays, these patients have fewer rejections, with an overall survival in the medium and long term similar to that of HTx in younger patients. These results have been achieved partly as a result of appropriate selection of recipients and emergence of new immunosuppressive agents that has allowed their use to be individualized to the characteristics and comorbidities of each patient. Despite the latest advances, longer-term multicenter studies are required to clarify the role of alternate lists and the impact of new ventricular assist devices in this population segment.

Pharmacogenetic study of ABCB1 and CYP3A5 genes during the first year following heart transplantation regarding tacrolimus or cyclosporine levels.

Pharmacogenetics explains part of the interindividual variability in drug responses. Many published works about the effects of single nucleotide polymorphisms (SNPs) on immunosuppressive drug blood levels present contradictory results. We evaluated the SNPs in ABCB1 (glycoprotein P) and CYP3A5 (metabolic enzyme) genes, seeking correlate them with tacrolimus or cyclosporine levels during the first year after heart transplantation. One blood sample was obtained from each of 41 patients: 26 treated with cyclosporine and 15 with tacrolimus. We characterize the SNPs rs1045642, 1128503, 2032582, 2235013, 2235033, 2229109, 3213619, 9282564 in ABCB1 and rs10264272, 776746 in CYP3A5 genes using the Sequenom platform. The genotype was correlated with the trough drug blood levels corrected by dose and body weight (C(0)/(dose/weight)). The CYP3A5 SNPs showed the expected behavior, where patients carrying the low expression variants displayed higher drug blood levels of more than 100% of the normal expression variant level even at 1 year posttransplantation. To correlate ABCB1 SNPs, the variants described to cause higher blood levels in rs1045642, 1128503, 2032582 (in linkage disequilibrium) showed this effect only until 4 months posttransplantation among patients treated with cyclosporine (more than 100% higher than the other variant). After 1 year, concentrations reached a stable phase with normal levels. The observation was not so evident among those treated with tacrolimus. Remarkably, at this point, patients treated with cyclosporine, showed a significant (P < .01) difference between the two variants of rs9282564 and even if it was not significant there was also a tendency among the intronic rs2235013 and 2235033. The results indicated that SNPs in ABCB1 gene seem to not be relevant for long-term dose adjustment in patients, but to show an effect during the first 4 months.

Relationship between functional capacity and quality of life in heart transplant patients.

The goal of heart transplantation (HT) is not only to prolong the life of patients with end-stage heart failure, but also to offer them the sort of health they enjoyed before the disease. It is widely known that patients' functional capacity improves after HT but what about their quality of life (QoL)? Do functional capacity and QoL improve simultaneously? In the present study, we compared the progression of effort capacity and QoL in the first 2 years after HT. A prospective longitudinal study was performed in 58 heart transplant recipients (43 males, 15 females, age 51.6 ± 10 years) able to complete an effort test 2, 6, 12, and 24 months after transplantation. The studied variables included the five dimensions of the Euroqol-5D questionnaire (EQ-5D) test: mobility, self-care, daily activities, pain/discomfort, anxiety, and depression; a visual analog scale from 0 to 100; and the results (metabolic equivalent units [METs] and time of exercise) of the effort test at 2, 6, 12, and 24 months after transplantation. Analysis of variance was used to compare these variables at each point. Significance was set at P < .05. Functional capacity, measured by both METs and time of exercise, improved progressively (METs: 2 months: 5.2 ± 1.8, 6 months: 6.6 ± 2.1, 12 months: 7.5 ± 2.2, and 24 months: 8.5 ± 2.3, P < .001). As well, the result of EQ-5D questionare improved in parallel to exercise capacity. However, visual analog scale score did not change significatively during the follow-up (2 months: 78.9.3 ± 16.1, 6 months: 83.8 ± 11.3, 12 months: 83.3 ± 11.1, 24 months: 85.2 ± 14.9; P = .192), reaching a plateau at 6 to 24 months. In conclusion, the improvement in functional capacity shown by heart transplant recipients in the first 2 years after transplantation was not parallel to the feelings of well-being measured by the analog scale of the EQ-5D. Possibly long after transplantation patients will compare themselves to healthy people rather than to their state before HT, resulting in improvements the visual analog scale.

Long-term prognostic implications of metabolic syndrome in heart transplant recipients.

BACKGROUND: Metabolic syndrome (MS) increases the risk of cardiovascular events due to endothelial dysfunction. There are few studies evaluating the impact of MS on the survival of heart transplantation (HTx) patients. AIM: The aim of this study was to study the impact of MS in the early period and on the long-term survival after HTx. MATERIALS AND METHODS: We studied 196 HTx patients with a minimum survival of 1 year post-HTx. A diagnosis of MS was made at 3 months after HTx, if at least 3 of the following criteria were met: triglyceride levels ≥150 mg/dL (or drug treatment for hypertriglyceridemia); high-density lipoprotein cholesterol (HDL-C) <40 mg/dL in men and <50 mg/dL in women (or drug treatment to raise HDL-C levels); diabetes mellitus on drug treatment or fasting glucose levels ≥100 mg/dL; blood pressure ≥130/85 mm Hg (or on antihypertensive drug treatment); and body mass index (BMI) ≥30. We used the Kaplan-Meier method (log-rank test) to calculate long-term survival and Student t and chi-square tests for comparisons. RESULTS: Among 196 patients, 96 developed MS. There were no differences between the groups with versus without MS in recipient gender, underlying etiology, smoking, pre-HTx diabetes, or immunosuppressive regimen. However, differences were observed between groups in age (MS: 53 ± 9 vs non-MS: 50 ± 12 years; P = .001); pre-HTx creatinine (MS: 1.2 ± 0.3 vs non-MS: 1.0 ± 0.4 mg/dL; P = .001); BMI (MS: 27.3 ± 4 vs non-MS: 24.6 ± 4; P = .001); pre-HTx hypertension (MS: 48% vs non-MS: 17%; P < .001); and dyslipidemia (MS: 53% vs non-MS: 37%; P = .023). Long-term survival was better among the non-MS group, but the difference did not reach significance (MS: 2381 ± 110 vs non-MS: 2900 ± 110 days; P = .34). CONCLUSIONS: The development of MS early after HTx is a common complication that affects nearly 50% of HTx patients. The prognostic implication of this syndrome on overall survival might occur in the long term.

Sympathetic reinnervation 1 year after heart transplantation, assessed using iodine-123 metaiodobenzylguanidine imaging.

Complete allograft denervation occurs during heart transplantation (HT). Partial ventricular sympathetic reinnervation that may develop after transplantation can be measured using iodine-123 meta iodobenzylguanidine (MIBG) uptake. Previous studies have suggested that reinnervation is likely to be a slow process, only occurring after 1 year posttransplantation. However, the reinnervation prevalence at 1 year after HT remains unknown. This study sought to determine sympathetic reinnervation measured by MIBG at 12 months after surgery. We performed serial cardiac MIBG imaging in 45 cardiac transplant recipients, including 32 males and 13 females, early (2 months) and late (12 months) after the operation. The intensity of myocardial MIBG uptaken was quantified by heart-to-mediastinum ratios (HMR). Reinnervation was considered when the HMR was >1.3. HMR was significantly higher at 12 months: 1.16 ± 0.10 at 2 vs 1.30 ± 0.15 at 12 months (P < .001). Eighteen (40%) of 45 subjects developed visible cardiac MIBG uptake at 1 year after transplantation with HMR >1.3. In conclusion, partial sympathetic reinnervation increases with time after HT; it was seen in 40% of patients at 1 year after the operation.

Proliferation signal inhibitors in heart transplantation: a 5-year experience.

INTRODUCTION: Calcineurin inhibitors (CNI) are associated with multiple complications, especially renal dysfunction and tumor development. Proliferation signal inhibitors (PSI) show renal protection and an antineoplastic effects, and may retard allograft vasculopathy. The objective of the current study was to present our initial experience center with PSI therapy. MATERIALS AND METHODS: We analyzed all heart transplants (HT) performed in our center who received a PSI at any time. We assessed the clinical profiles, indications for and strategies of PSI introduction, complications, causes of discontinuation, and renal functional evolutions. RESULTS: Among 604 HT performed in our center, 82 patients (13.5%) received a PSI: sirolimus (n=2) or everolimus (n=80). Their mean age was 53±12 years and 90% were men. PSI introduction occurred at 75±53 months posttransplantation. The strategy was CNI minimization in 17% of cases, and total conversion from CNI in 83%. The PSI indication was renal dysfunction (40%), tumors (38%), allograft vasculopathy (17%), and other reasons (5%). After PSI introduction, 15.8% of patients suffered a rejection episode and 20%, a significant infection. The PSI discontinuation rate was 8.5%: due to infection (2.4%), edema (1.2%), inadequate cicatrization (1.2%), and other reasons (3.7%). Creatinine was 1.68±0.64 mg/dL the year before and 1.72±0.79 mg/dL at and 1.82±1.61 mg/dL 1 year after PSI conversion. CONCLUSION: PSIs showed few complications with a low withdrawal rate, and maintained renal function. The main indications for their use were renal dysfunction, tumors, or development of allograft vasculopathy.

Timing, etiology, and location of first infection in first year after heart transplantation.

BACKGROUND: Infections are the leading cause of death in the first year after heart transplantation (HTx) after the postoperative period. OBJECTIVE: To describe the timing, etiology, and location of the first infection occurring in the first year after HTx. PATIENTS AND METHODS: The study included 604 HTx procedures performed at our center from November 1987 to September 2009. Infections were classified as those requiring hospital admission or that prolonged hospital stay. Infection was established on the basis of clinical findings and supplementary test results. Etiologic diagnosis was established at microbiological culture. Infections were categorized as bacterial, viral, fungal, protozoal, or of unknown origin, and were grouped according to microorganism family. Time to occurrence of infection is given as mean (interquartile range). Locations considered were systemic, pulmonary, genitourinary, cutaneous, oropharyngeal, mediastinal, sternal, gastrointestinal, and other. RESULTS: Mean (SD) patient age was 51 (12) years, and 83.8% of patients were men. Almost half of all patients (42.9%) experienced some type of infection in the first year after HTx. The most frequently occurring infections were bacterial (49.6%) and viral (38.7%), with fewer fungal (6.3%), protozoal (1.2%), and of unknown origin (4.3%). Staphylococci were the most commonly isolated organisms (10.5%) in bacterial infections, cytomegalovirus (21.1%) in viral infections, and Candida (2.3%) and Aspergillus (2.3%) in fungal infections. Early-onset infections (n=2; 1-7 days) were caused by Candida spp, and late-onset infections (n=110; 14-182 days) by a mixed group of bacteria. The sternum was the site of early-onset infections (n=9; 6-14 days), and the genitourinary tract was the site of late-onset infections (n=110; 28-180 days). CONCLUSIONS: Nearly half of HTx recipients experience a significant infection during the first year posttransplantation. Early-onset infections occur in critical care units, are caused by nosocomial organisms, and involve the sternum or mediastinum, whereas late- onset infections have a more varied etiology and preferentially affect the skin and genitourinary tract.

Mycophenolate acid vs mycophenolate mofetil therapy.

BACKGROUND: Mycophenolate mofetil (MMF) is included in the basic immunosuppression regimen in heart transplantation (HTx). Classically, the mycophenolic acid (MPA) concentration has not been considered to provide clinical information. OBJECTIVE: To perform a comparative analysis of MMF dosage and MPA concentration and their effect on post-HTx renal function. PATIENTS AND METHODS: Sixty patients underwent HTx between January 2007 and April 2009, and were followed up at 4 scheduled visits in 6 months. The standard MMF dose was 1000 mg/12 h, with adjustment according to clinical criteria. The MPA concentration was determined using an enzyme-multiplied immunoassay (EMIT 2000; Siemens Healthcare Diagnostics Inc, Deerfield, Illinois), without change in dosage. The correlation between mean MMF dosage and MPA concentrations at all visits vs renal function values was analyzed using serum creatinine concentration, creatinine clearance (CrCl; Modification of Diet in Renal Disease), and glomerular filtration rate (GFR; Cockcroft-Gault formula). RESULTS: Mean (SD) patient age was 50 (13) years, and 45 of 60 (75.4%) were men. Pre-HTx values were as follows: creatinine concentration, 1.13 (0.47) mg/dL; CrCl, 81.59 (36.84) mL/min/1.73 m2; and GFR, 77.46 (30.60) mL/min. In the first 6 months post-HTx, significant negative correlations were observed between mean MPA concentration and creatinine concentration (r=.42; P=.001), CrCl (r=-.36; P=.01), and GFR (r=-.45; P=.001). No correlation was observed with mean MMF dosage. CONCLUSION: There are important differences in the relationship of MPA concentration vs MMF dosage and post-HTx renal function. Although studies with a larger number of patients are needed, treatment guided by MPA concentration seems reliable for evaluation of renal function.

Can we accept donors who have suffered a resuscitated cardiac arrest?

INTRODUCTION AND AIMS: The shortage of donor organs has prompted increased acceptance of hearts from donors with more comorbidities. With increasing frequency, hearts are being offered from patients who have undergone a resuscitated cardiac arrest (RCA). Our aim was to compare the rate of complications in the postoperative and follow-up periods, depending on whether the transplanted organ came from a donor who had undergone an RCA. MATERIALS AND METHODS: We included all 604 heart transplantations (HTs) performed in our center from 1987 to 2009, including 25 recipients who received an organ from a donor who had undergone RCA. We considered RCA to be an in-hospital cardiac arrest that was resuscitated from the onset, with a duration of <30 minutes, and with total recovery of cardiac and hemodynamic function. We analyzed ischemia time, incidence of acute graft failure (AGF), intubation period, recovery room stay, and long-term survival. The statistical methods were Student t and chi-square tests. RESULTS: There were no differences in baseline characteristics, except that patients in the RCA group were younger (47±13 vs 51±11 years; P=.50). There were also no differences between the RCA group and the other patients in ischemia time (151±50 vs 154±53 minutes; P=.826), incidence of AGF (33% vs 24.7%; P=.311), hours of intubation (76±204 vs 72±249; P=.926), days of recovery room stay (6±7 vs 8±6; P=.453), or survival after HT (53±54 vs 53±52 months; P=.982). CONCLUSIONS: Patients receiving a heart from a patient with an in-hospital RCA and subsequent hemodynamic stability have a similar outcomes to other HT patients.

Clinical predictors of immunotolerance in heart transplantation.

BACKGROUND AND AIM: The drugs routinely administered to prevent rejection often cause lethal side effects. Tolerant patients, therefore, should be identified to minimize these problems. The aim of this analysis was to identify clinical variables that may be associated with tolerance. METHODS: We recruited 522 heart transplants (HT), excluding combined procedures, retransplantations, pediatric recipients, and subjects who died in the first year to obtain a cohort of 375 patients. Two groups were distinguished by the presence of echocardiographic, clinical, or pathological evidence of rejection in the first year (15 echocardiograms and 10 protocol biopsies per patient); 99 tolerant patients were compared with 276 nontolerant patients. We analyzed clinical variables related to morbidity and mortality. RESULTS: The univariate analysis showed few differences between the groups. The multivariate analysis showed that only major histocompatibility complex (MHC)-A and MHC-DR matched recipients were significantly associated with tolerance. Thus, the likelihood of tolerance was increased by 1.7- and 2.8-fold if 1 or 2 MHC-I matches were present and by 3.4- and 3.7-fold if 1 or 2 MHC-DR matches were present, respectively survival curves showed significant differences (P=.034). Most deaths in both groups were related to immunosuppressive drugs; among tolerant subjects, deaths were due to infection and neoplasms and among nontolerant patients, deaths were due to chronic rejection, neoplasms, and infection. CONCLUSIONS: The only clinical parameter that can determined whether a HT recipient was tolerant was MHC-A and MHC-DR matching. If there is matching, a reduced immunosuppressive load should be prescribed to prevent drug toxicity.

Normalization of the heart rate response to exercise 6 months after cardiac transplantation.

INTRODUCTION: Heart transplant recipients show an abnormal heart rate (HR) response to exercise due to complete cardiac denervation after surgery. They present elevated resting HR, minimal increase in HR during exercise, with maximal HR reached during the recovery period. The objective of this study was to study the frequency of normalization of the abnormal HR in the first 6 months after transplantation. MATERIALS AND METHODS: We prospectively studied 27 heart transplant recipients who underwent treadmill exercise tests at 2 and 6 months after heart transplantation (HT). HR responses to exercise were classified as normal or abnormal, depending on achieving all of the following criteria: (1) increased HR for each minute of exercise, (2) highest HR at the peak exercise intensity, and (3) decreased HR for each minute of the recovery period. The HR response at 2 months was compared with the results at 6 months post-HT. RESULTS: At 2 months post-HT, 96.3% of the patients showed abnormal HR responses to exercise. Four months later, 11 patients (40.7%) had normalized HR responses (P<.001), which also involved a significant decrease in the time to achieve the highest HR after exercise (124.4±63.8 seconds in the first test and 55.6±44.6 seconds in the second). A significant improvement in exercise capacity and chronotropic competence was also shown in tests performed at 6 months after surgery. CONCLUSIONS: We observed important improvements in HR responses to exercise at 6 months after HT, which may represent early functional cardiac reinnervation.

Mortality from renal dysfunction in heart transplant patients: creatinine versus glomerular filtration rate.

INTRODUCTION: One of the most common, significant problems after heart transplantation (HT) is the development of renal dysfunction. In recent years, the glomerular filtration rate (GFR) has replaced the serum creatinine as the standard parameter for its determination. Our objective was to analyze which renal function parameter (creatinine or GFR) at 1 year after HT better classified patients who will die during follow-up. PATIENTS AND METHODS: The study included 316 consecutive HT patients surviving at least 1 year after transplantation. Creatinine and GFR were determined by the Modification of Diet in Renal Disease Study (MDRD4) equation. Mortality during the follow-up was analyzed to compare both parameters using receiver operating characteristic curves. RESULTS: Over a mean follow-up of 6±3 years, 97 patients died (30.7%). At 1 year after HT, the patients who succumbed displayed a significantly higher mean creatinine value (1.63±0.65 vs 1.41±0.64 mg/dL; P=.004) and a more decreased GFR (53.8 vs 60.8 mL/min/1.73 m2; P=.006). Both groups had the same area under the curve, 0.61 (95% confidence interval: 0.54-0.68; P=.002). CONCLUSION: Among our population, GFR calculated by the abbreviated MDRD4 equation did not provide any additional prognostic value to serum creatinine at 1 year after HT to predict long-term mortality.

Post-heart transplant tumors: chronology and impact on survival.

INTRODUCTION AND AIMS: Tumors are the second leading cause of death beyond the first year heart transplantation (HT). The aim of our study was to establish a chronology for the occurrence and the impact on overall survival of de novo neoplasms after HT. MATERIALS AND METHODS: We included 597 patients undergoing HT from January 1987 to December 2008. De novo tumors were classified into groups: Kaposi's sarcoma, melanoma, epidermoid skin carcinoma, other skin tumors, lung neoplasms, bladder tumors, prostate adenocarcinoma, digestive tumors, lymphomas, and other tumors. We based the study on the median value and interquartile range of the tumors to estimate their occurrence. Survival rates were calculated using Kaplan-Meier curves and the log-rank tests. We included only patients with survivals beyond 1 year after HT. RESULTS: A total of 109 tumors developed during the follow-up. There were no differences in the survival of patients who lived more than 1 year regarding the development or not of a tumor (155±8 vs 179±6 months; P=.177). CONCLUSIONS: The incidence of tumor occurrence after HT was high (18.25%). There were several periods in which the occurrence of certain tumors was more frequent, while other periods appeared to be tumor-free. As most tumors were skin cancers, their impact on overall survival was low.

Preliminary results of a prospective randomized study of cyclosporine versus tacrolimus in the development of cardiac allograft vasculopathy at 1 year after heart transplantation.

INTRODUCTION AND AIMS: Cardiac allograft vasculopathy (CAV) is the leading cause of death after the first year post-heart transplantation (HT). Numerous factors have been implicated in the development of CAV. The aim of this prospective randomized study was to assess the impact of cyclosporine (CsA) and tacrolimus (Tac) on the development of CAV. MATERIALS AND METHODS: From November 2006 to October 2008, 49 HT patients in our center were randomized to receive CsA or Tac. The additional treatment for all patients consisted of daclizumab induction and maintenance treatment with mycophenolate mofetil (1 g/12 hours) and steroids (withdrawal was not attempted). Thirteen patients died before coronary arteriography plus intravascular ultrasound of the left anterior descending artery was performed at 1 year after HT. Hence, the final number of patients included was 36 (18 per group). We considered significant CAV to be the presence of intimal proliferation>1 mm and/or>0.5 mm in 180°. The statistical methods were Student t and chi-square tests. RESULTS: There were no differences in baseline characteristics between the two groups. Nor were there significant differences in maximum intimal proliferation between the groups (CsA 0.65±0.29 vs Tac 0.82±0.51 mm; P=.292) or in the development of significant CAV when both criteria were combined (CsA 31.6% vs Tac 38.9%; P=.642). CONCLUSIONS: One year after HT, no differences were detected in the development of significant CAV according to the type of calcineurin inhibitor used when combined with daclizumab induction and maintenance treatment with mycophenolate mofetil and steroids.

Lymphomas in heart transplant recipients: do antivirals protect against the neoplastic effect of anti-CD3 monoclonal antibody?

INTRODUCTION AND AIM: After cardiac allograft vasculopathy, tumors are the second leading cause of death among heart transplantation (HT) patients after the first year. Lymphomas are tumors of lymphocytic origin whose development has been associated with the use of anti-CD3 monoclonal antibody (OKT3). Some studies suggest that the use of acyclovir could counteract this effect. Our aim was to investigate the impact of gancyclovir on OKT3 and lymphoma development after HT. MATERIALS AND METHODS: We included all 239 HTs performed in our center from 1989 to 2002. We divided patients into those who received gancyclovir treatment (prophylaxis, pre-emptive therapy, or for cytomegalovirus infection) versus those who did not receive this agent at any time during follow-up (88 vs 151 patients). The statistical methods were Student's t and chi-square tests. RESULTS: There were no differences in the baseline characteristics of the patients--gender, recipient age, etiology leading to HT, diabetes, and dyslipidemia--except for a higher rate of hypertension among the group who did not receive gancyclovir (73.7 vs 60.2%; P=.03). None of the 7 patients who developed lymphomas during the follow-up received gancyclovir (0 vs 4.6%; P=.040). CONCLUSIONS: Antivirals may have a relevant role to neutralize potential neoplastic effects (especially lymphomas) associated with the use of OKT3 induction therapy.

Exercise tolerance after beta blockade in recent cardiac transplant recipients.

OBJECTIVE: Exercise capacity has been shown to be reduced among cardiac transplant recipients. This observation is directly connected to both the transplanted heart's dependence on circulating catecholamines and the abnormal sympathoadrenal response to exercise in these patients. Taking into account this background, there is reluctance to use beta-blockers after heart transplantation. Nevertheless, this point remains controversial. Our aim was to examine exercise tolerance after an oral dose of atenolol early after cardiac transplantation. MATERIALS AND METHODS: Eighteen nonrejecting, otherwise health, cardiac transplant recipients were included in this study at a mean of 61.9 +/- 25.6 days after surgery; 13 were men. Patients performed controlled exercise to a symptom-limited maximum before and 2 hours after taking an oral dose of atenolol. Heart rate, blood pressure, exercise time, and metabolic equivalent units (METS) were recorded at rest as well as during and after exercise. We compared results depending on taking atenolol. RESULTS: Resting (101.7 +/- 14.5 vs 84 +/- 12.4 bpm; P = .001) and peak heart rates (128.5 +/- 12.9 vs 100.7 +/- 16 bpm; P = .001) were significantly higher before than after beta blockade. Resting systolic blood pressure was slightly higher before compared with after beta blockade (129.3 +/- 23.6 vs 122.2 +/- 20.3 mm Hg; P = .103). However, there was neither a significant difference in the length of exercise (3.17 +/- 1.96 vs 3.40 +/- 2.48 minutes; P = .918) nor in the estimated oxygen consumption (METS; 5.07 +/- 1.8 vs 5.31 +/- 2.2; P = .229). Furthermore, no patient reported a greater degree of tiredness after beta blockade. CONCLUSIONS: This study showed little adverse effect on exercise tolerance by beta blockade in recently transplanted patients. Atenolol seemed to be safe in this context.