Registro español de trasplante cardiaco. XXXIII informe oficial de la Asociación de Insuficiencia Cardiaca de la Sociedad Española de Cardiología / Spanish Heart Transplant Registry. 33rd official report of the Heart Failure Association of the Spanish Society of Cardiology

Introducción y objetivos Se actualizan los datos anuales de Registro español de trasplante cardiaco con los hallazgos de los procedimientos realizados en 2021. Métodos Se describen las principales características clínicas, del tratamiento recibido y de los resultados en términos de supervivencia del año 2021 y las tendencias en el periodo 2012-2020. Resultados En 2021 se han realizado 302 trasplantes cardiacos (un 8,6% más que el año anterior). En 2021 se ha confirmado la tendencia observada en años anteriores a una disminución de los trasplantes urgentes y a la realización de estos mayoritamente con dispositivos de asistencia ventricular. Las demás características y los resultados en términos de supervivencia muestran una clara tendencia a la estabilización en la última década. Respecto a 2019, en los años de la pandemia por SARS-CoV-2 (2020 y 2021) no se detecta un impacto relevante en los resultados en la fase aguda tras el trasplante y en la serie histórica. Conclusiones En 2021 se ha recuperado la actividad de trasplante hasta cifras previas a la pandemia por SARS-CoV-2, que no ha tenido un impacto global significativo en los resultados. Las características del procedimiento y los resultados muestran una clara tendencia a la estabilización en la última década (AU)

Introduction and objectives This report updates the annual data of the Spanish heart transplant registry with the procedures performed in 2021. Methods We describe the clinical profile, therapeutic characteristics and outcomes in terms of survival of the procedures performed in 2021. Their temporal trends are updated for the 2012 to 2020 period. Results In 2021, 302 heart transplants were performed (8.6% increase versus 2020). The tendency in 2021 confirmed that of prior years, with fewer urgent transplants and a preference for the use of ventricular assist devices. The remaining characteristics and survival showed a clear trend toward stability in the last decade. Compared with 2019, the SARS-CoV-2 pandemic (2020 and 2021) did not affect short- or long-term survival. Conclusions In 2021, transplant activity returned to prepandemic levels. The SARS-CoV-2 pandemic did not significantly affect transplant outcomes. The main transplant features and outcomes have clearly stabilized in the last decade (AU)

Consenso sobre el manejo de la hiperpotasemia en pacientes con insuficiencia cardíaca: recomendaciones de la SEC-SEMI / Consensus on the management of hyperkalemia in patients with heart failure: recommendations from the SEC-SEMI

n los pacientes con insuficiencia cardíaca (IC) y fracción de eyección reducida, el uso de los inhibidores del sistema renina-angiotensina-aldosterona (iSRAA) se asocia con una mejoría funcional, incremento de la calidad de vida percibida, reducción de la probabilidad de muerte cardiovascular y disminución del número de hospitalizaciones. Algunos de esos fármacos también resultan eficaces en pacientes con enfermedad renal crónica y albuminuria, así como en pacientes con hipertensión arterial resistente. A pesar de sus numerosos beneficios, los iSRAA se asocian a un incremento de la incidencia de hiperpotasemia, sobre todo en pacientes con insuficiencia renal crónica concomitante. La hiperpotasemia es un trastorno iónico frecuente que se define como la elevación de las concentraciones plasmáticas de potasio por encima de 5 mEq/L, y se ha relacionado con la presencia de rehospitalizaciones, arritmias cardíacas malignas y aumento de la mortalidad. Por otro lado, un tratamiento optimizado con iSRAA requiere de incrementos progresivos de las dosis que pueden suponer a su vez una mayor probabilidad de hiperpotasemia. Por todo ello, es necesario establecer unas directrices para el manejo y tratamiento de estos pacientes. Con este objetivo surge este documento de consenso, cuyas recomendaciones han sido elaboradas por un grupo de 10 expertos y revisado por un panel de otros 10 especialistas en el tratamiento de pacientes con IC (en total 10 cardiólogos y 10 internistas). El documento ha sido avalado por la Sociedad Española de Cardiología (SEC) y la Sociedad Española de Medicina Interna (SEMI) (AU)

Use of renin-angiotensin-aldosterone system inhibitors (RAASi) in patients with heart failure (HF) and reduced ejection fraction is associated with functional improvement, an increase in perceived quality of life, a reduction in the probability of cardiovascular death, and a decrease in the number of hospitalizations. Some of these drugs are also efficacious in patients with chronic kidney disease and albuminuria as well as in patients with resistant hypertension. Despite their numerous benefits, RAASi are associated with an increase in incidence of hyperkalemia, especially in patients with concomitant chronic kidney disease. Hyperkalemia is a common electrolyte disorder that is defined as an elevation in plasma concentrations of potassium above 5 mEq/L. It has been related to rehospitalizations, malignant arrhythmias, and an increase in mortality. On the other hand, optimized treatment with RAASi requires progressive dose increases which can in turn entail a greater probability of hyperkalemia. For all of these reasons, it is necessary to establish management and treatment guidelines for these patients. This consensus document arises from this objective. Its recommendations have been developed by a group of ten experts and reviewed by a panel of another ten specialists in the treatment of patients with HF (ten cardiologists and ten internists in total). This document has been endorsed by the Spanish Society of Cardiology (SEC, for its initials in Spanish) and the Spanish Society of Internal Medicine (SEMI, for its initials in Spanish) (AU)

Complicaciones infecciosas relacionadas con la asistencia circulatoria mecánica de corta duración en candidatos a trasplante cardiaco urgente / Infectious complications associated with short-term mechanical circulatory support in urgent heart transplant candidates

Introducción y objetivos: El uso de dispositivos de asistencia circulatoria mecánica de corta duración como puente a trasplante es frecuente en España. Se desconocen la epidemiología y la repercusión de las complicaciones infecciosas en estos pacientes. Métodos: Descripción sistemática de la epidemiología y análisis de la repercusión pronóstica de las complicaciones infecciosas en un registro multicéntrico retrospectivo de pacientes tratados con dispositivos de asistencia circulatoria mecánica de corta duración como puente a trasplante cardiaco urgente entre 2010 y 2015 en 16 hospitales españoles. Resultados: Se estudió a 249 pacientes; 87 (34,9%) de ellos tuvieron un total de 102 infecciones. La vía respiratoria fue la localización más frecuente (n=47; 46,1%). En 78 casos (76,5%) se obtuvo confirmación microbiológica; se aislaron en total 100 gérmenes causales, con predominio de bacterias gramnegativas (n=58, 58%). Los pacientes con complicaciones infecciosas presentaron mayor mortalidad durante el periodo de asistencia circulatoria mecánica (el 25,3 frente al 12,3%; p=0,009) y menor probabilidad de recibir un trasplante (el 73,6 frente al 85,2%; p=0,025) que los pacientes sin infección. La mortalidad posoperatoria tras el trasplante fue similar en ambos grupos (con infección, el 28,3%; sin infección, el 23,4%; p=0,471). Conclusiones: Los pacientes tratados con dispositivos de asistencia circulatoria mecánica de corta duración como puente al trasplante cardiaco están expuestos a un alto riesgo de complicaciones infecciosas, las cuales se asocian con una mayor mortalidad en espera del órgano (AU)

Introduction and objectives: Short-term mechanical circulatory support is frequently used as a bridge to heart transplant in Spain. The epidemiology and prognostic impact of infectious complications in these patients are unknown. Methods: Systematic description of the epidemiology of infectious complications and analysis of their prognostic impact in a multicenter, retrospective registry of patients treated with short-term mechanical devices as a bridge to urgent heart transplant from 2010 to 2015 in 16 Spanish hospitals. Results: We studied 249 patients, of which 87 (34.9%) had a total of 102 infections. The most frequent site was the respiratory tract (n=47; 46.1%). Microbiological confirmation was obtained in 78 (76.5%) episodes, with a total of 100 causative agents, showing a predominance of gram-negative bacteria (n=58, 58%). Compared with patients without infection, those with infectious complications showed higher mortality during the support period (25.3% vs 12.3%, P=.009) and a lower probability of receiving a transplant (73.6% vs 85.2%, P=.025). In-hospital posttransplant mortality was similar in the 2 groups (with infection: 28.3%; without infection: 23.4%; P=.471). Conclusions: Patients supported with temporary devices as a bridge to heart transplant are exposed to a high risk of infectious complications, which are associated with higher mortality during the organ waiting period (AU)

Resultados del retrasplante cardiaco: subanálisis del Registro Español de Trasplante Cardiaco / Results of heart retransplantation: subanalysis of the Spanish Heart Transplant Registry

Introducción y objetivos: El retrasplante cardiaco (ReTC) representa un tema controvertido actualmente. Nuestro objetivo es describir y analizar los resultados del ReTC en España. Métodos: Análisis retrospectivo del Registro Español de Trasplante Cardiaco de 1984 a 2018. Se recogieron datos sobre donante, receptor, cirugía, inmunosupresión y supervivencia. La mortalidad por todas las causas o la necesidad de ReTC postrasplante fueron el objetivo principal. Se estudiaron diferencias en supervivencia según indicación, tiempo entre trasplantes y época del ReTC. Resultados: Se estudiaron en total 7.592 trasplantes cardiacos (TxC) y 173 (2,3%) ReTC (mediana de edad, 52,0 y 55,0 años respectivamente). La enfermedad vascular del injerto fue la indicación de ReTC más frecuente (42,2%) y 59 pacientes (80,8%) recibieron el ReTC más de 5 años después del trasplante inicial. El rechazo agudo y el fallo primario del injerto disminuyeron como indicaciones durante el periodo estudiado. La insuficiencia renal, la hipertensión, la necesidad de ventilación mecánica o balón intraaórtico y la mayor duración de la isquemia fría fueron más frecuentes en el ReTC. La mediana de seguimiento del ReTC fue 5,8 años. El ReTC tuvo peor supervivencia que el TxC (HR ponderado=1,43; IC95%, 1,17-1,44; p<0,001). El rechazo agudo (HR=2,49; IC95%, 1,45-4,27; p<0,001) se relacionó con el peor resultado. El ReTC más allá de 5 años del trasplante inicial presagia resultados similares a los del TxC primario (HR ponderado=1,14; IC95%, 0,86-1,50; p<0,001). Conclusiones: El ReTC se asoció con mayor mortalidad que el TxC, especialmente por rechazo agudo. El pronóstico del ReTC realizado más de 5 años después es similar al del TxC primario (AU)

Introduction and objectives: Heart retransplantation (ReHT) is controversial in the current era. The aim of this study was to describe and analyze the results of ReHT in Spain. Methods: We performed a retrospective cohort analysis from the Spanish Heart Transplant Registry from 1984 to 2018. Data were collected on donors, recipients, surgical procedure characteristics, immunosuppression, and survival. The main outcome was posttransplant all-cause mortality or need for ReHT. We studied differences in survival according to indication for ReHT, the time interval between transplants and era of ReHT. Results: A total of 7592 heart transplants (HT) and 173 (2.3%) ReHT were studied (median age, 52.0 and 55.0 years, respectively). Cardiac allograft vasculopathy was the most frequent indication for ReHT (42.2%) and 59 patients (80.8%) received ReHT >5 years after the initial transplant. Acute rejection and primary graft failure decreased as indications over the study period. Renal dysfunction, hypertension, need for mechanical ventilation or intra-aortic balloon pump and longer cold ischemia time were more frequent in ReHT. Median follow-up for ReHT was 5.8 years. ReHT had worse survival than HT (weighted HR, 1.43; 95%CI, 1.17-1.44; P<.001). The indication of acute rejection (HR, 2.49; 95%CI, 1.45-4.27; P<.001) was related to the worst outcome. ReHT beyond 5 years after initial HT portended similar results as primary HT (weighted HR, 1.14; 95%CI, 0.86-1.50; P<.001). Conclusions: ReHT was associated with higher mortality than HT, especially when indicated for acute rejection. ReHT beyond 5 years had a similar prognosis to primary HT (AU)

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.

Consensus on the management of hyperkalemia in patients with heart failure: Recommendations from the SEC-SEMI.

Use of renin-angiotensin-aldosterone system inhibitors (RAASi) in patients with heart failure (HF) and reduced ejection fraction is associated with functional improvement, an increase in perceived quality of life, a reduction in the probability of cardiovascular death, and a decrease in the number of hospitalizations. Some of these drugs are also efficacious in patients with chronic kidney disease and albuminuria as well as in patients with resistant hypertension. Despite their numerous benefits, RAASi are associated with an increase in incidence of hyperkalemia, especially in patients with concomitant chronic kidney disease. Hyperkalemia is a common electrolyte disorder that is defined as an elevation in plasma concentrations of potassium above 5 mEq/L. It has been related to rehospitalizations, malignant arrhythmias, and an increase in mortality. On the other hand, optimized treatment with RAASi requires progressive dose increases which can in turn entail a greater probability of hyperkalemia. For all of these reasons, it is necessary to establish management and treatment guidelines for these patients. This consensus document arises from this objective. Its recommendations have been developed by a group of ten experts and reviewed by a panel of another ten specialists in the treatment of patients with HF (ten cardiologists and ten internists in total). This document has been endorsed by the Spanish Society of Cardiology (SEC, for its initials in Spanish) and the Spanish Society of Internal Medicine (SEMI, for its initials in Spanish).

Molecular dynamics and protein frustration analysis of human fused in Sarcoma protein variants in Amyotrophic Lateral Sclerosis type 6: An In Silico approach.

Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disorder. The disease is characterized by degeneration of upper and lower motor neurons, leading to death usually within five years after the onset of symptoms. While most cases are sporadic, 5%-10% of cases can be associated with familial inheritance, including ALS type 6, which is associated with mutations in the Fused in Sarcoma (FUS) gene. This work aimed to evaluate how the most frequent ALS-related mutations in FUS, R521C, R521H, and P525L affect the protein structure and function. We used prediction algorithms to analyze the effects of the non-synonymous single nucleotide polymorphisms and performed evolutionary conservation analysis, protein frustration analysis, and molecular dynamics simulations. Most of the prediction algorithms classified the three mutations as deleterious. All three mutations were predicted to reduce protein stability, especially the mutation R521C, which was also predicted to increase chaperone binding tendency. The protein frustration analysis showed an increase in frustration in the interactions involving the mutated residue 521C. Evolutionary conservation analysis showed that residues 521 and 525 of human FUS are highly conserved sites. The molecular dynamics results indicate that protein stability could be compromised in all three mutations. They also affected the exposed surface area and protein compactness. The analyzed mutations also displayed high flexibility in most residues in all variants, most notably in the interaction site with the nuclear import protein of FUS.

Linking a European cohort of children born with congenital anomalies to vital statistics and mortality records: A EUROlinkCAT study.

EUROCAT is a European network of population-based congenital anomaly (CA) registries. Twenty-one registries agreed to participate in the EUROlinkCAT study to determine if reliable information on the survival of children born with a major CA between 1995 and 2014 can be obtained through linkage to national vital statistics or mortality records. Live birth children with a CA could be linked using personal identifiers to either their national vital statistics (including birth records, death records, hospital records) or to mortality records only, depending on the data available within each region. In total, 18 of 21 registries with data on 192,862 children born with congenital anomalies participated in the study. One registry was unable to get ethical approval to participate and linkage was not possible for two registries due to local reasons. Eleven registries linked to vital statistics and seven registries linked to mortality records only; one of the latter only had identification numbers for 78% of cases, hence it was excluded from further analysis. For registries linking to vital statistics: six linked over 95% of their cases for all years and five were unable to link at least 85% of all live born CA children in the earlier years of the study. No estimate of linkage success could be calculated for registries linking to mortality records. Irrespective of linkage method, deaths that occurred during the first week of life were over three times less likely to be linked compared to deaths occurring after the first week of life. Linkage to vital statistics can provide accurate estimates of survival of children with CAs in some European countries. Bias arises when linkage is not successful, as early neonatal deaths were less likely to be linked. Linkage to mortality records only cannot be recommended, as linkage quality, and hence bias, cannot be assessed.

[Traumatic aneurysm of the middle meningeal artery associated with an epidural hematoma]. / Aneurisma traumatico de la arteria meningea media en el contexto de un hematoma epidural.

TITLE: Aneurisma traumatico de la arteria meningea media en el contexto de un hematoma epidural.

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.

The falling incidence of hematologic cancer after heart transplantation.

BACKGROUND: A number of changes in the management of heart transplantation (HT) patients have each tended to reduce the risk of post-HT hematologic cancer, but little information is available concerning the overall effect on incidence in the HT population. METHODS: Comparison of data from the Spanish Post-Heart-Transplantation Tumour Registry for the periods 1991-2000 and 2001-2010. RESULTS: The incidence among patients who underwent HT in the latter period was about half that observed in the former, with a particularly marked improvement in regard to incidence more than five yr post-HT. CONCLUSIONS: Changes in HT patient management have jointly reduced the risk of hematologic cancer in the Spanish HT population. Long-term risk appears to have benefited more than short-term risk.

Steroid withdrawal during 5 years following heart transplantation, and the relationship between steroid dosage at 1-year follow-up and complications during the next 2 years: results from the RESTCO study.

BACKGROUND: Little information is available regarding the controversial issue of steroid withdrawal following heart transplantation (HT), or instead in the incidence of adverse steroid effects at dosages typically employed in Spain. METHODS: We analyzed the 5-year follow-up records of 1209 patients (82.5% men, aged ≥ 18 years) who underwent HT between 2000 and 2005 and survived at least 1 month in 13 Spanish centers. The incidences of first steroid withdrawal before 1, 3, and 5 years post-HT were expressed as Kaplan-Meier probability estimates. Three patient groups defined in accordance with steroid dosage at 1-year follow-up (0, ≤ 5, and >5 mg/d; groups A, B, and C, respectively) were compared with regard to the incidence of de novo hypertension, diabetes, and bone fractures over the following 2 years. RESULTS: The 5-year incidence of withdrawal was 28%, 21% of whom required reintroduction of steroids. Kaplan-Meier probabilities of withdrawal before 1, 3, and 5 years post-HT were 8.8% (95% confidence interval ([CI] 7.3%-10.7%), 27.8% (CI 25.2%-30.6%), and 30.2% (CI 27.5%-33.2%), respectively. At 1-year follow-up, 9.9% of patients were steroid-free, 28.9% were taking ≤ 5 mg/d, and 61.3% >5 mg/d. The 2-year incidence of de novo hypertension increased significantly (P = .012) from 13.5% to 29.6% to 35.3% in groups A, B, and C respectively. These groups did not differ significantly in regard to the 2-year incidence of diabetes or bone fractures. CONCLUSIONS: Reintroduction of steroids was required by 21% of the 28% of Spanish HT patients who has been weaned from steroids within 5 years of HT. The incidence of de novo hypertension between 1 and 3 years post-HT increased with steroid dosage at 1-year follow-up. De novo diabetes and bone fractures showed no similar significant association.

Influence of steroid dosage, withdrawal, and reinstatement on survival after heart transplantation: results from the RESTCO study.

BACKGROUND: Little information is available regarding the consequences of steroid withdrawal following heart transplantation (HT) in Spain. METHODS: We analyzed the records of 1068 patients (81.6% men) who underwent HT between 2000 and 2005 in 13 Spanish centers who were aged ≥ 18 years and who survived at least 1 year. Death rates and Kaplan-Meier survival curves for 1 to 5 years post-HT were compared among four groups: groups A and B, patients on steroids throughout the first 5 years post-HT at dosages of ≤ 5 mg/d between 1-year and 5-year follow-up (group A; n = 148), or >5 mg/d for some part of this period (group B; n = 578). Groups C and D were patients from whom steroids were at some point withdrawn including group D (n = 73) with and group C (n = 269) without subsequent reintroduction into the maintenance regimen. RESULTS: Steroids were withdrawn at 1.6 ± 0.9 years post-HT in group C, and 1.7 ± 1.2 years post-HT in group D. The death rate between 1- and 5-year follow-up (deaths per 1000 person-years) was 44.3% (95% confidence interval 26.2-62.5) in group A, 42.6% (33.7-51.4) in group B, 30.5% (19.6-41.4) in group C, and 47.8% (21.8-73.7) in group D. There was no significant difference among them or among Kaplan-Meier survival curves of the four groups (P = .34 in both cases). Comparison of combined groups C + D with groups A + B showed no evidence of a greater mortality among combined groups C + D. CONCLUSIONS: The late withdrawal of steroids following HT was not associated with increased mortality.

High-Bandpass Filters in Electrocardiography: Source of Error in the Interpretation of the ST Segment.

Introduction. Artifactual variations in the ST segment may lead to confusion with acute coronary syndromes. Objective. To evaluate how the technical characteristics of the recording mode may distort the ST segment. Material and Method. We made a series of electrocardiograms using different filter configurations in 45 asymptomatic patients. A spectral analysis of the electrocardiograms was made by discrete Fourier transforms, and an accurate recomposition of the ECG signal was obtained from the addition of successive harmonics. Digital high-pass filters of 0.05 and 0.5 Hz were used, and the resulting shapes were compared with the originals. Results. In 42 patients (93%) clinically significant alterations in ST segment level were detected. These changes were only seen in "real time mode" with high-pass filter of 0.5 Hz. Conclusions. Interpretation of the ST segment in "real time mode" should only be carried out using high-pass filters of 0.05 Hz.

[Multidisciplinary approach to the endolymphatic sac tumour]. / Abordaje multidisciplinar al tumor de saco endolinfático.

INTRODUCTION: Papilar adenocarcinoma of endolymphatic sac is related with Von Hippel Lindau disease at 15% of cases, has a slow growing with a high local aggressiveness, and doesn't metastasize. It causes symptoms of Meniere's syndrome due to the compression that produces at endolymphatic duct. When it presents with hearing loss is usually sudden and irreversible manner. The diagnostic is made with image tests and analysis of its structure with immunohistochemical tests. The elective treatment is surgical remove, and its main complication the perioperative bleeding it can be avoided with preoperative embolization or stereotactic radiation. CASE REPORT: A case of endolymphatic sac tumour is presented, in a 17-years-old male with unilateral deafness and crisis of rotate vertigo, with family history of Von Hippel-Lindau disease. Perceptive deafness and right vestibular arreflexia are detected at technical exploration. In a petrous bone computer tomography appears a mass at vestibular aqueduct. We performed a petrosectomy with presigmoidal approach and saving of inner ear. Pathological analysis revealed an endolymphatic sac tumour. DISCUSSION: In patients with a family history of Von Hippel Lindau disease and clinical symptoms of vertigo and normal hearing or with slight hearing loss we should suspect the presence of endolymphatic sac tumor. The clinical presentation of hearing loss can be sudden and irreversible even with negative or inconclusive images. Therefore, a quick action is important for the preservation of this function.

Abordaje multidisciplinar al tumor de saco endolinfático / Multidisciplinary approach to the endolymphatic sac tumour

Introducción. El adenocarcinoma papilar de saco endolinfático se asocia a la enfermedad de Von Hippel Lindau en el 15% de los casos, tiene un crecimiento lento pero elevada agresividad local, y no metastatiza. Clínicamente produce un Síndrome de Menière derivado de la compresión que provoca en el conducto endolinfático. Cuando debuta con pérdida de audición suele ser de forma brusca e irreversible. Se diagnostica con técnicas de imagen y el análisis de su estructura con inmunohistoquímica. Su tratamiento electivo es la exéresis quirúrgica, y su principal complicación el sangrado perioperatorio, que se puede evitar con embolización o radiación estereotáctica preoperatorio.Caso clínico. Presentamos un caso de un tumor de saco endolinfático en un paciente de 17 años aquejado de sordera unilateral y crisis de vértigo rotatorio, con antecedentes familiares de enfermedad de Von Hippel Lindau. Las pruebas complementarias mostraron una hipoacusia neurosensorial y una arreflexia vestibular derechas. En tomografía computarizada de peñascos se apreciaba una lesión en el acueducto vestibular. Se sometió al paciente a una petrosectomía con abordaje presigmoideo y preservación de laberinto, realizándose una exéresis total de la lesión. Se diagnosticó de tumor del saco endolinfático en el análisis anatomopatológico.Discusión. Ante un paciente con antecedentes familiares de enfermedad de Von Hippel Lindau y un cuadro clí-nico de vértigo incluso sin hipoacusia, o siendo esta leve, habría que pensar en la presencia de un tumor del saco endolinfático. La presentación clínica de sordera puede ser brusca e irreversible, incluso con imágenes negativas o poco concluyentes, por lo que una rápida actuación es importante para la preservación de esta función (AU)

Introduction. Papilar adenocarcinoma of endolymphatic sac is related with Von Hippel Lindau disease at 15% of cases, has a slow growing with a high local aggressiveness, and doesn’t metastasize. It causes symptoms of Meniere’s syndrome due to the compression that produces at endolymphatic duct. When it presents with hearing loss is usually sudden and irreversible manner. The diagnostic is made with image tests and analysis of its structure with immunohistochemical tests. The elective treatment is surgical remove, and its main complication the perioperative bleeding it can be avoided with preoperative embolization or stereotactic radiation.Case report. A case of endolymphatic sac tumour is presented, in a 17-years-old male with unilateral deafness and crisis of rotate vertigo, with family history of Von Hippel-Lindau disease. Perceptive deafness and right vestibular arreflexia are detected at technical exploration. In a petrous bone computer tomography appears a mass at vestibular aqueduct. We performed a petrosectomy with presigmoidal approach and saving of inner ear. Pathological analysis revealed an endolymphatic sac tumour.Discussion. In patients with a family history of Von Hippel Lindau disease and clinical symptoms of vertigo and normal hearing or with slight hearing loss we should suspect the presence of endolymphatic sac tumor. The clinical presentation of hearing loss can be sudden and irreversible even with negative or inconclusive images. Therefore, a quick action is important for the preservation of this function (AU)

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.