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Background: This observational cohort study compared the likelihood of maintained (stabilized/up-titrated) renin-angiotensin-aldosterone system inhibitor (RAASi) therapy at 6 months following hyperkalaemia in patients with chronic kidney disease (CKD) and/or heart failure (HF) from the USA, Japan and Spain who received sodium zirconium cyclosilicate (SZC) for at least 120 days, relative to those with no prescription for a potassium (K + ) binder., Methods: Using health registers and hospital medical records, patients with CKD and/or HF receiving RAASi therapy who experienced a hyperkalaemia episode were identified. Propensity score (PS) matching (1:4) was applied to balance the SZC cohort to the no K + binder cohort on baseline characteristics. Logistic regression analysis was performed to compare the odds of maintained RAASi therapy at 6 months in the SZC versus no K + binder cohorts., Results: The PS-matched SZC cohort included 565 (USA), 776 (Japan) and 56 (Spain) patients; the no K + binder cohort included 2068, 2629 and 203 patients, respectively. At 6 months, 68.9% (USA), 79.9% (Japan) and 69.6% (Spain) in the SZC cohorts versus 53.1% (USA), 56.0% (Japan) and 48.3% (Spain) in the no K + binder cohorts had maintained RAASi therapy. Meta-analysed across countries, the odds ratio of maintained RAASi therapy in the SZC cohort versus no K + binder cohort was 2.56 (95% confidence interval 1.92-3.41; P  < .0001)., Conclusions: In routine clinical practice across three countries, patients treated with SZC were substantially more likely to maintain guideline-concordant RAASi therapy at 6 months following hyperkalaemia relative to patients with no K + binder treatment., Competing Interests: A.R. has received research grants and consulting fees from AstraZeneca. C.V.P. Jr has received consultancy fees from AstraZeneca. I.J.S.L. is an employee of Hospital Universitari i Politècnic La Fe and has served on the speakers bureaus of AstraZeneca and Novartis. E.L. is an employee and stockholder of AstraZeneca. M.A. is an employee of AstraZeneca. S.F. is an employee and stockholder of AstraZeneca. A.A. is an employee and stockholder of AstraZeneca. I.H. is an employee of Atrys Health, a service company for AstraZeneca. T.M. has received honoraria for lectures from AstraZeneca. E.K. reports no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.) more...

Disturbances in sphingolipid metabolism lead to biological function dysregulation in many diseases, but it has not been described in heart failure (HF). Sphingosine-1-phosphate (S1P) levels have not ever been measured in the myocardium. Therefore, we analyze the gene dysregulation of human cardiac tissue by mRNA-seq ( n = 36) and ncRNA-seq ( n = 50). We observed most major changes in the expression of genes belonging to de novo and salvage pathways, and the tight gene regulation by their miRNAs is largely dysregulated in HF. We verified using ELISA ( n = 41) that ceramide and S1P accumulate in HF cardiac tissue, with an increase in the ceramide/S1P ratio of 57% in HF. Additionally, changes in left ventricular mass and diameters are directly related to CERS1 expression and inversely related to S1P levels. Altogether, we define changes in the main components of the sphingolipid metabolism pathways in HF, mainly de novo and salvage, which lead to an increase in ceramide and S1P in cardiac tissue, as well as an increase in the ceramide/S1P ratio in HF patients. Therapeutic gene modulation focused on restoring ceramide levels or reversing the ceramide/S1P ratio could be a potential therapy to be explored for HF patients. more...

Arrhythmogenic left ventricular cardiomyopathy (ALVC) is a rare heritable heart-muscle disorder characterized by a progressive loss of left ventricular myocardium and its replacement by fibrofatty tissue. Myocarditis is an inflammatory disease of the heart that may occur secondary to infections, immune system activation or exposure to drugs. Hot phases of ALVC present with chest pain and troponin rise, mimicking acute viral myocarditis and indicate a progression of the disease. Recently, myocarditis has also been described as an infrequent complication of coronavirus disease 2019 (Covid-19) mRNA vaccines. We herein report for the first time a case of probable myocarditis induced by Covid-19 vaccine in a patient with previous medical history of ALVC. We aim to highlight the common characteristics of ALVC and Covid-19 vaccine myocarditis and work through the differential diagnosis of these two entities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Alania-Torres, Morillas-Climent, García-Escrivá, Vinueza-Buitrón, Poquet-Catalá, Zorio, Sánchez-Lázaro, Galcerá-Jornet and Valle-Muñoz.) more...

Imaging techniques play a main role in heart failure (HF) diagnosis, assessment of aetiology and treatment guidance. Echocardiography is the method of choice for its availability, cost and it provides most of the information required for the management and follow up of HF patients. Other non-invasive cardiac imaging modalities, such as cardiovascular magnetic resonance (CMR), nuclear imaging-positron emission tomography (PET) and single-photon emission computed tomography (SPECT) and computed tomography (CT) could provide additional aetiological, prognostic and therapeutic information, especially in selected populations. This article reviews current indications and possible future applications of imaging modalities to improve the management of HF patients., Competing Interests: Disclosure: The authors have no conflicts of interest to declare. more...

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., (Copyright © 2015 Elsevier Inc. All rights reserved.) more...

Aims: The objectives of this study were to analyse the effect of heart failure (HF) on several proteins of nuclear pore complex (NPC) and their relationship with the human ventricular function., Methods and Results: A total of 88 human heart samples from ischemic (ICM, n = 52) and dilated (DCM, n = 36) patients undergoing heart transplant and control donors (CNT, n = 9) were analyzed by Western blot. Subcellular distribution of nucleoporins was analysed by fluorescence and immunocytochemistry. When we compared protein levels according to etiology, ICM showed significant higher levels of NDC1 (65%, p<0.0001), Nup160 (88%, p<0.0001) and Nup153 (137%, p = 0.004) than those of the CNT levels. Furthermore, DCM group showed significant differences for NDC1 (41%, p<0.0001), Nup160 (65%, p<0.0001), Nup153 (155%, p = 0.006) and Nup93 (88%, p<0.0001) compared with CNT. However, Nup155 and translocated promoter region (TPR) did not show significant differences in their levels in any etiology. Regarding the distribution of these proteins in cell nucleus, only NDC1 showed differences in HF. In addition, in the pathological group we obtained good relationship between the ventricular function parameters (LVEDD and LVESD) and Nup160 (r = -0382, p = 0.004; r = -0.290, p = 0.033; respectively)., Conclusions: This study shows alterations in specific proteins (NDC1, Nup160, Nup153 and Nup93) that compose NPC in ischaemic and dilated human heart. These changes, related to ventricular function, could be accompanied by alterations in the nucleocytoplasmic transport. Therefore, our findings may be the basis for a new approach to HF management. more...

Background: An alteration of the autonomic nervous system has been described in heart failure (HF). The aim of this study was to assess, compare and relate the impairment of both arms of the autonomic nervous systems, the sympathetic and parasympathetic (SNS and PNS) in a same group of patients., Methods: We analyzed 23 patients with advanced HF (NYHA III-IV/IV and IV/IV) and EF<35% who were on the waiting list for heart transplantation. We assessed the SNS by determining cardiac uptake of (123)I metaiodobenzylguanidine, and analyzed the heart mediastinum rate (HMR) and the myocardial washout rate (WR). The PNS was assessed by 24-hour Holter ECG recording and subsequent analyses of heart rate turbulence (HRT) in which turbulence onset (TO) and turbulence slope (TS) were determined., Results: In the study of the SNS, HMR values were 1.32 ± 0.12, and WR 0.36 ± 0.1. Higher creatinine levels were associated with a lower WR (r=-0.604; p=0.02). In the study of the SNP, TO was higher the lower the LVEF (r=-0.410; p=0.052), and age was associated with a lower TS (r=-0.4; p=0.059). In the study of the relationships between the SNS and PNS, HMR was correlated in a nearly significant manner with TO (r=-0.399; p=0.059) and WR with TS (r=-0.447; p=0.033)., Conclusions: In stable patients with advanced HF (NYHA III-IV and IV/IV), a significant and parallel impairment occurs in both arms of the autonomic nervous system. This could have prognostic implications and would help to prioritize patients on the waiting list for heart transplantation., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.) more...

Background: Cyclosporine (CsA) and tacrolimus (Tac) in heart transplantation (HTx) have been compared but with certain drawbacks. We compared both drugs in a prospective analysis with medium-term follow-up., Methods: Hundred and six patients were randomized to receive CsA or Tac (53 per group). Target levels of CsA were 200-300 ng/mL in the first six months and 100-200 ng/mL thereafter. Tac levels were 10-15 and 5-10 ng/mL, respectively. We also used daclizumab as induction and mycophenolate mofetil (MMF) and steroids as maintenance therapy., Results: Baseline characteristics were similar. Survival (CsA 88.7% vs. Tac 81.1%; p = 0.493) was similar. There was a tendency for longer time to first rejection with CsA (93 ± 110 vs. 55 ± 81 d; p = 0.122). There were more rejection-free patients with Tac (39 vs. 28%; p = 0.233). CsA patients suffered more viral infections (0.41 ± 0.58 vs. 0.11 ± 0.31; p = 0.003). CsA patients developed hypertension often (64 vs. 43%; p = 0.032). Tac patients suffered more gastrointestinal complications (16 vs. 6%; p = 0.042). Renal function and the development of diabetes, dyslipidemia, or neurological complications was similar., Conclusions: Tac patients showed a tendency for longer time to first rejection, and there were more rejection-free patients with Tac and suffered fewer viral infections. Tac patients developed less hypertension and needed less drugs for its control. Renal function was similar in both groups., (© 2010 John Wiley & Sons A/S.) more...

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., (Copyright © 2011 Elsevier Inc. All rights reserved.) more...

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., (Copyright © 2011 Elsevier Inc. All rights reserved.) more...

Daclizumab is an interleukin-2 receptor antagonist which is used for induction therapy in heart transplant patients. It has few side effects and is associated with a low infection rate. Postoperative renal failure after heart transplantation is common and potentially fatal. The administration of calcineurin inhibitors in the postoperative period can aggravate the situation. We report the cases of six patients who underwent heart transplantation and developed acute renal failure in the immediate postoperative period. All were administered daclizumab weekly to avoid the introduction of calcineurin inhibitors and to facilitate recovery of renal function. Calcineurin inhibitors were introduced only once renal function had improved. Renal function recovered in all cases and there was a low complication rate. The administration of repeated doses of daclizumab to patients who experience acute postoperative renal failure after heart transplantation may provide an alternative therapeutic approach that enables calcineurin inhibitors to be avoided and, consequently, renal function to recover., (Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.) more...

This study aimed to determine if there are differences in inflammatory markers in the acute phase between systolic heart failure and heart failure with preserved systolic function. One hundred and thirty-one patients with acute heart failure were recruited consecutively. At admission, plasma fibrinogen, C-reactive protein, sialic acid, von Willebrand factor, vascular endothelial growth factor, interleukin-6 and NTproBNP were all evaluated. If the ejection fraction was 45% or over patients were included in the HF-PSF group; the remaining patients were included in the SHF group. The HF-PSF patients were older (72±10 vs 63±12 years, P<0.001), presented a higher rate of atrial fibrillation (56.1 vs 21.3%, P<0.001), and had a lower rate of hemoglobin (12.2±2 vs 13.3±2.1 g/dL, P<0.01). No significant differences were observed in the inflammation markers analyzed among SHF and HF-PSF groups. In the acute phase of heart failure there is a marked elevation of inflammatory markers but there are no differences in the inflammatory markers analyzed between the two different types of heart failure. more...

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., (Copyright © 2010 Elsevier Inc. All rights reserved.) more...

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., (Copyright © 2010 Elsevier Inc. All rights reserved.) more...

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., (Copyright © 2010 Elsevier Inc. All rights reserved.) more...

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., (Copyright © 2010 Elsevier Inc. All rights reserved.) more...

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., (Copyright © 2010 Elsevier Inc. All rights reserved.) more...

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., (Copyright © 2010 Elsevier Inc. All rights reserved.) more...

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., (Copyright © 2010 Elsevier Inc. All rights reserved.) more...

Background: This study was performed to determine the factors that cause arterial hypertension after heart transplantation (HT) and the drugs used in its management., Materials and Methods: We studied 247 consecutive patients who had undergone HT between 2000 and 2006 and who survived for at least 6 months. We excluded patients who received combination transplants, those who underwent repeat transplantation, and pediatric patients who had received transplants. Hypertension was defined as the need to use drugs for its control. Renal dysfunction was defined as serum creatinine concentration greater than 1.4 mg/dL, and diabetes as the need for an antidiabetes drug for its control. Statistical analyses were performed using the t test, the chi(2) test, and Cox regression., Results: Mean (SD) patient age was 52 (10) years, and 87.4% of the patients were men. Follow-up was 72 (42) months. Hypertension was present in 33.3% of patients before HT and in 71.1% at some time after HT. The number of drugs used to control hypertension was 1.3 (0.5); one drug was used in 72.9% of patients. The most often used single class of drugs were calcium channel blockers (63.2%), followed by angiotensin-converting enzyme inhibitors (20%), and angiotensin receptor blockers (15.8%). Only pre-HT hypertension was significantly associated with greater use of antihypertensive drugs post-HT (mean [SD], 1.48 [0.65] vs 1.22 [0.41]; P = .005). At univariate analysis, only pre-HT hypertension was associated with the presence of post-HT hypertension (80.5% vs 65.5%; P = .02). At Cox regression analysis, recipient age (P = .02) and pre-HT hypertension (P = .004) were associated with post-HT hypertension., Conclusions: Hypertension is common after HT; however, in most patients, it can be controlled with a single antihypertensive agent. The most important factors in the development of hypertension are the presence of pre-HT hypertension and advanced age. more...

Unlabelled: The application of clinical trials (CTs) to daily practice is based on the assumption that the patients included in these trials are similar to those seen on a daily basis. We performed a retrospective study to evaluate patient survival depending on whether they were included in a CT. We studied 217 patients who underwent heart transplantation (HT) between January 2000 and September 2006. We excluded patients who received combination transplants, those who underwent repeat HT, and pediatric patients who underwent HT. In total, 54 patients were included in a CT and 163 were not (NCT). The statistical tests included the t test, the chi(2) test and the Kaplan-Meier method., Results: Patients in the NCT group were in worse condition at HT, with a greater percentage of inotropic treatments pre-HT (36% vs 17%; P = .005), emergency transplants procedures (30% vs 13%; P = .01), and worse functional status pre-HT (P = .03). The NCT group exhibited lower survival (80.37% vs 87.04%; P = 0.13, log-rank test). There were no significant differences in the other analyzed variables., Conclusions: Patients included in CTs tend to have better long-term survival rates, for several reasons: patients in the CT group were more stable at HT (selection bias), and the close follow-up of patients in CTs makes it more likely that any complication will be detected and treated early (follow-up bias). more...

Background: Patients undergoing urgent heart transplantation (HT) have a poorer prognosis and more long-term complications. The objective of this study was to compare the preoperative course in patients undergoing urgent HT according to the need for preoperative intra-aortic balloon counterpulsation (IABP)., Materials and Methods: We studied 102 consecutive patients including 23 patients with IABP who underwent urgent HT between January 2000 and September 2006. We excluded patients who received combination transplants, those who underwent repeat HT, and pediatric patients who underwent HT. The statistical methods used were the t test for quantitative variables and the chi(2) test for qualitative variables. A logistic regression model was constructed to assess the possible relationship between IABP and other variables on premature death within 30 days after HT., Results: Mean (SD) patient-age was 50 (10) years. No significant differences were observed in baseline characteristics between the IABP and the non-IAPB groups. The IABP patient group had higher rates of acute graft failure (45.5% vs 35.4%; P = .46) and premature death (18.8% vs 14.8%; P = .67) and shorter long-term survival (40.6 [34.9] vs 54.5 [43.7] mo; P = .30). Multivariate analysis demonstrated no association between the need for IABP and increased frequency of premature death., Conclusions: Use of IABP is not associated with premature or late death. We recommend use of IABP in patients with acute decompensated heart failure to stabilize them before HT. more...

Background: Renal dysfunction is a serious problem after heart transplantation (HT). The objective of this study was to determine the cardiovascular risk factors associated with medium- to long-term dysfunction after HT., Materials and Methods: We studied 247 consecutive patients who underwent HT between January 2000 and September 2006 who survived for at least 6 months. We excluded patients receiving combination transplants, those undergoing repeat HT, and pediatric patients undergoing HT. Mean (SD) follow-up was 72 (42) months. We defined renal dysfunction as serum creatinine concentration greater than 1.4 mg/dL during follow-up. Patients were considered to be smokers if they had smoked during the six months before HT, to have hypertension if they required drugs for blood pressure control, and to have diabetes if they required insulin therapy. Statistical tests included the t test and the chi(2) tests. We performed Cox regression analysis using significant or nearly significant values in the univariate analysis., Results: Mean (SD) age of the patients who underwent HT was 52 (10) years, and 217 (87.9%) were men. Renal dysfunction was detected during follow-up in 135 (54.5%) patients. The significant variables at univariate analysis were smoking (61.4% vs. 43.2%; P = .01) and previous renal dysfunction (94.1% vs 52.7%; P = .001). Nearly significant variables were the presence of hypertension before HT (63.8% vs 51.1%; P = .09) and after HT (58.2% vs 44.8%; P = .082). At multivariate analysis, pre-HT smoking and previous renal dysfunction were significant correlates (P = .04 and P = .01, respectively)., Conclusions: Renal dysfunction is common after HT. In our analysis, the best predictors were pre-HT dysfunction and smoking. Less important factors were advanced age and post-HT hypertension. more...

Introduction: Up to 95% of the patients with heart transplantation (HT) suffer from arterial hypertension (AHT). The development of de novo AHT after HT has not been greatly studied., Aim: To identify the predictor variables for the development of de novo AHT after HT., Materials and Methods: We retrospectively studied 253 patients with HT and who did not previously have AHT. We excluded cases of early mortality, re-transplants and combined transplants. We considered AHT as the constant need to take anti-hypertensive drugs to maintain blood pressure < 140/90 mmHg. We studied all the variables relating to recipient, donor, surgical procedure, immunosuppression and follow-up. The statistics used were the Student's t-test, chi-square statistic and a logistic regression analysis., Results: Of the 253 patients, 109 (43%) developed AHT. The variables associated with more prevalent AHT were male recipient/donor, idiopathic dilated cardiomyopathy (IDCM) as cause of HT, having been a smoker as well as renal deterioration (RD) and hypercholesterolemia after HT. The multivariate analysis found smoking prior to the HT and hypercholesterolemia during follow-up as independent risk factors and urgent HT as a protective variable., Conclusions: AHT after HT is frequent. The variables associated in our population were smoking before HT, male recipient/donor, IDCM prior to HT and hypercholesterolemia and RD after HT. more...

Background: Cardiac allograft vasculopathy (CAV) is the leading cause of death heart transplant (HT) recipients after the first year. We assessed the influence of cardiovascular risk factors (CVRFs) in HT recipients on the development of CAV after 1 year of follow-up., Materials and Methods: From 2001 to 2005, we studied 72 patients who received a HT and survived for at least 1 years. All patients underwent coronary arteriography and intravascular ultrasonography at 1 year after HT. Cardiac allograft vasculopathy was defined as intimal proliferation of 0.5 mm or more. The analyzed CVRFs were age, sex, body mass index, diabetes mellitus, hypertension, dyslipidemia, and smoking. We also considered the heart disease that was the reason for HT. The statistical tests used in the univariate analysis were the t and chi(2) tests. Logistic regression was performed with the variables obtained at univariate analysis., Results: Mean (SD) recipient age at HT was 51 (9) years. Eighty patients (90.5%) were men. Dyslipidemia was significantly associated with a greater incidence of CAV at 1 year (68.3% vs 41.9%; P = .03). Ischemia, as opposed to all other causes, was also significantly associated with CAV (69.4% vs 44.4%; P = .03). Older age, hypertension, smoking history, and high body mass index were associated with a higher incidence of CAV, albeit without statistical significance. At multivariate analysis, dyslipidemia was the most significant CVRF (P = .045) for the development of CAV., Conclusions: Recipient dyslipidemia is a risk factor for the development of CAV in HT. The remaining traditional CVRFs are more weakly associated with CAV. After HT close monitoring of recipients with pretransplantation CVRFs is essential for early detection of CAV. more...

Introduction and Objectives: While it appears to be clear that an inflammatory process occurs in heart failure (HF), it is still to be defined whether inflammation depends to a greater extent on HF etiology, functional class (FC), or the extent of depression of ejection fraction (EF). Our objectives were to analyze differences in inflammatory marker levels as compared to a healthy population, to assess differences depending on HF etiology, and to relate values with FC and EF., Patients and Methods: Fifty-nine consecutive outpatients with stable HF (57 + or - 9 years, 89% males) and 59 controls (55 + or - 8 years, 85% males) were enrolled into the study. Causes of HF included ischemic heart disease (n=24), idiopathic dilated cardiomyopathy (n=24), and miscellaneous conditions (n=11). Patients with decompensation in the past 6 months were excluded from the study. Protein fibrinogen, sialic acid, C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-alpha) were measured. Echocardiography was performed in all study patients. FC was assessed using the NYHA classification., Results: A comparison of inflammatory marker levels between the HF and control groups showed significant differences in all markers, except for TNF-alpha. Protein fibrinogen in controls: 253 + or - 54 mg/dl, protein fibrinogen in HF: 294 + or - 67 mg/dl; p<0.05. Sialic acid in controls: 53 + or - 1 mg/dl, sialic acid in HF: 61 + or - 12 mg/dl; p<0.05. CRP in controls: 1.3 + or - 0.7 mg/dl, CRP in HF: 7.8 + or - 1.2 mg/dl; p<0.05. TNF-alpha in controls: 183 + or - 51 ng/ml, TNF-alpha in HF: 203 + or - 13 ng/ml; p=0.2. No differences were found between the different etiologies of HF. A positive association was seen between FC and protein fibrinogen and TNF-alpha (p<0.05), but not with EF., Conclusions: Increased inflammatory marker levels related to FC of the patient, but not to EF, are found in chronic HF. more...

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. more...

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. more...