Grado de consecución de los objetivos lipídicos a largo plazo en una cohorte de pacientes con síndrome coronario agudo en práctica clínica real / Achievement of long-term lipid targets in a cohort of patients with acute coronary syndrome in real-world clinical practice

Introduction and objectives According to the recent European epidemiological studies, the degree of lipid control in patients with very high vascular risk is suboptimal. This study analyzes the epidemiological characteristics, cardiovascular risk factors, lipid profile, recurrence, and degree of achievement of long-term lipid targets, according to the ESC/EAS Guidelines, in a cohort of patients with acute coronary syndrome (ACS) in a real-world clinical practice setting. Methods This work is a retrospective cohort study of patients diagnosed with ACS admitted to the Coronary Unit of a tertiary hospital from January 1, 2012 to December 31, 2015 and followed-up on until March 2022. Results A total of 826 patients were studied. During the follow-up period, greater prescribing of combined lipid-lowering therapy was observed, mainly high- and moderate-intensity statins and ezetimibe. At 24 months after the ACS, 33.6% of living patients had LDL levels <70 mg/dl and 9.3% had LDL levels <55 mg/dl. At the end of the follow-up (101 [88–111] months), the corresponding figures were 54.5% and 21.1%. Some 22.1% of patients had a recurrent coronary event and only 24.6% achieved an LDL level <55 mg/dl. Conclusions Achievement of the LDL targets recommended by the ESC/EAS guidelines is suboptimal in patients with ACS, both at two years and in the long-term (7–10 years), especially in patients with recurrent ACS (AU)

Introducción y objetivos Según los recientes estudios epidemiológicos europeos, el grado de control lipídico de los pacientes de muy alto riesgo vascular es subóptimo. En este estudio se han analizado las características epidemiológicas, los factores de riesgo cardiovascular, el perfil lipídico, la recurrencia y el grado de consecución de los objetivos lipídicos a largo plazo, según las Guías ESC/EAS, en una cohorte de pacientes con síndrome coronario agudo (SCA), en condiciones de práctica clínica real. Métodos Estudio de cohorte retrospectivo de los pacientes con diagnóstico de SCA ingresados en la unidad coronaria de un hospital de tercer nivel, entre el 1 de enero de 2012 y el 31 de diciembre de 2015, y seguidos hasta marzo de 2022. Resultados Se estudiaron 826 pacientes. Durante el periodo de seguimiento se observó una mayor prescripción de terapia hipolipemiante combinada, principalmente estatinas de alta y moderada intensidad y ezetimibe. A los 24 meses del SCA, un 33,6% de los pacientes vivos tenían un LDL < 70 mg/dl y en un 9,3% los niveles eran < 55 mg/dl. Al final del seguimiento (101 [88–111] meses), las correspondientes cifras eran del 54,5 y 21,1%. Un 22,1% de los pacientes presentaron un evento coronario recurrente, y solamente un 24,6% de ellos alcanzaron un nivel de LDL < 55 mg/dl. Conclusiones El cumplimiento de los objetivos recomendados por las Guías ESC/EAS en pacientes con SCA, es subóptimo, tanto a los 2 años como a largo plazo (7-10 años) desde el evento, y en especial en los pacientes con SCA recurrente (AU)

Achievement of long-term lipid targets in a cohort of patients with acute coronary syndrome in real-world clinical practice.

INTRODUCTION AND OBJECTIVES: According to the recent European epidemiological studies, the degree of lipid control in patients with very high vascular risk is suboptimal. This study analyzes the epidemiological characteristics, cardiovascular risk factors, lipid profile, recurrence, and degree of achievement of long-term lipid targets, according to the ESC/EAS Guidelines, in a cohort of patients with acute coronary syndrome (ACS) in a real-world clinical practice setting. METHODS: This work is a retrospective cohort study of patients diagnosed with ACS admitted to the Coronary Unit of a tertiary hospital from January 1, 2012 to December 31, 2015 and followed-up on until March 2022. RESULTS: A total of 826 patients were studied. During the follow-up period, greater prescribing of combined lipid-lowering therapy was observed, mainly high- and moderate-intensity statins and ezetimibe. At 24 months after the ACS, 33.6% of living patients had LDL levels <70 mg/dl and 9.3% had LDL levels <55 mg/dl. At the end of the follow-up (101 [88-111] months), the corresponding figures were 54.5% and 21.1%. Some 22.1% of patients had a recurrent coronary event and only 24.6% achieved an LDL level <55 mg/dl. CONCLUSIONS: Achievement of the LDL targets recommended by the ESC/EAS guidelines is suboptimal in patients with ACS, both at two years and in the long-term (7-10 years), especially in patients with recurrent ACS.

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)

Sensibilización durante la asistencia circulatoria de corta duración. Determinantes, tratamiento y pronóstico después del trasplante cardiaco / Sensitization during short-term mechanical circulatory support. Determinants, therapeutic management, and outcomes after heart transplant

Introducción y objetivos: El desarrollo de anticuerpos contra antígenos leucocitarios humanos es una complicación conocida de la asistencia ventricular de larga duración. El propósito del presente estudio es evaluar su incidencia durante el empleo de dispositivos de asistencia ventricular de corta duración (DAVC) (CentriMag), sus determinantes y su repercusión en los resultados del trasplante cardiaco. Métodos: Estudio retrospectivo con pacientes tratados con DAVC como puente al trasplante entre 2009 y 2019. Se consideró sensibilización un panel reactivo de anticuerpos calculado> 10%. Las variables de respuesta fueron supervivencia y supervivencia libre de rechazo agudo (RA). Resultados: Se trató con DAVC a 89 pacientes, con una mediana de edad de 56,0 [intervalo intercuartílico, 50,0-59,9] años y el 16,8% de mujeres, durante una mediana de 23,6 [16,6-35,0] días. El 12,4% se sensibilizó durante la asistencia. El único determinante independiente de la sensibilización fue el sexo femenino (OR=8,67; IC95%, 1,93-38,8; p=0,005). De los 89 pacientes, 21 fallecieron durante la asistencia y 68 se sometieron a trasplante. De los pacientes trasplantados, 8 (11,8%) fallecieron y 20 (29,4%) tuvieron algún episodio de RA tras un seguimiento promedio de 49,6 ±31,2 meses tras el trasplante. Tras ajuste multivariable, la sensibilización aumentó el riesgo de RA (HR=3,64; IC95%, 1,42-9,33; p=0,007), con una tendencia no significativa a mayor mortalidad (HR=4,07; IC95%, 0,96-17,3; p=0,057). Conclusiones: La sensibilización relacionada con los DAVC es posible, predomina en el sexo femenino y se asocia de manera significativa con el RA, con una tendencia no significativa a mayor mortalidad (AU)

Introduction and objectives: The development of human-leukocyte antigen antibodies is a well-known adverse effect of the use of long-term ventricular assist devices (VADs). The aim of this study was to determine the incidence of sensitization during short-term mechanical circulatory support with VAD (CentriMag), its determinants, and its impact on posttransplant outcomes. Methods: We performed a retrospective review of patients who were bridged to transplant with short-term VAD from 2009 to 2019. Sensitization was defined as a calculated panel-reactive antibody> 10%. The endpoints included overall survival and rejection-free survival. Results: A total of 89 patients (median age 56.0 [interquartile range, 50.0-59.9] years, 16.8% female) received a short-term VAD as a bridge to transplant. The median duration of support was 23.6 [interquartile range, 16.6-35.0] days. Eleven patients (12.4%) became sensitized during support. The only factor significantly associated with sensitization was female sex (OR, 8.67; 95%CI, 1.93–38.8; P=.005). Of the 89 patients, 21 patients died during support; 68 patients underwent heart transplant. After a mean follow-up of 49.6 ±31.2 months, 8 patients (11.8%) died and 20 (29.4%) had at least 1 rejection episode. On multivariate analysis, sensitization was an independent predictor of acute rejection (HR, 3.64; 95%CI, 1.42-9.33; P=.007), with a nonstatistically significant trend to higher mortality (HR, 4.07; 95%CI, 0.96-17.3; P=.057). Conclusions: Sensitization with short-term VADs can occur and is significantly associated with female sex and with rejection. Sensitization also showed a nonstatistically significant trend to higher mortality (AU)

Impacto de la variabilidad intrapaciente en la concentración sanguínea de anticalcineurínicos en los resultados del trasplante cardiaco / Impact of intrapatient blood level variability of calcineurin inhibitors on heart transplant outcomes

Introducción y objetivos: El objetivo es estudiar el impacto clínico de la variabilidad intrapaciente (VIP) de la concentración sanguínea de los anticalcineurínicos en el trasplante cardiaco, pues la información actual es escasa. Métodos: Se analizó retrospectivamente a pacientes de edad≥18 años con un trasplante cardiaco realizado entre 2000 y 2014 y con supervivencia≥1 año. La VIP se valoró mediante el coeficiente de variación de concentraciones entre los meses 4 a 12 postrasplante. El compuesto de rechazo, mortalidad o pérdida del injerto y la mortalidad o pérdida del injerto 1-5 años tras el trasplante se analizaron mediante regresión de Cox. Resultados: Se estudió a 1.581 receptores (edad, 56 años; mujeres, 21%), tratados con ciclosporina (790 pacientes) o tacrolimus (791 pacientes). En el análisis multivariable, un coeficiente de variación> 27,8% tendió a asociarse con el compuesto de rechazo/mortalidad (HR=1,298; IC95%, 0,993-1,695; p=0,056) y con la mortalidad (HR=1,387; IC95%, 0,979-1,963; p=0,065) a los 5 años. La asociación con el rechazo fue significativa al analizar a la población sin rechazos durante el primer año del trasplante (HR=1,609; IC95%, 1,129-2,295; p=0,011). El tacrolimus tuvo menos VIP que la ciclosporina, junto con unos mejores resultados por la menor influencia de la VIP. Conclusiones: La VIP de los anticalcineurínicos, especialmente con la inmunosupresión basada en el tacrolimus, se asocia solo marginalmente con los resultados a medio plazo del trasplante cardiaco, aunque puede tener influencia en los pacientes más estables durante el primer año tras el trasplante (AU)

Introduction and objectives: Intrapatient blood level variability (IPV) of calcineurin inhibitors has been associated with poor outcomes in solid-organ transplant, but data for heart transplant are scarce. Our purpose was to ascertain the clinical impact of IPV in a multi-institutional cohort of heart transplant recipients. Methods: We retrospectively studied patients aged ≥18 years, with a first heart transplant performed between 2000 and 2014 and surviving≥ 1 year. IPV was assessed by the coefficient of variation of trough levels from posttransplant months 4 to 12. A composite of rejection or mortality/graft loss or rejection and all-cause mortality/graft loss between years 1 to 5 posttransplant were analyzed by Cox regression analysis. Results: The study group consisted of 1581 recipients (median age, 56 years; women, 21%). Cyclosporine immediate-release tacrolimus and prolonged-release tacrolimus were used in 790, 527 and 264 patients, respectively. On multivariable analysis, coefficient of variation> 27.8% showed a nonsignificant trend to association with 5-year rejection-free survival (HR, 1.298; 95%CI, 0.993-1.695; P=.056) and with 5-year mortality (HR, 1.387; 95%CI, 0.979-1.963; P=.065). Association with rejection became significant on analysis of only those patients without rejection episodes during the first year posttransplant (HR, 1.609; 95%CI, 1.129-2.295; P=.011). The tacrolimus-based formulation had less IPV than cyclosporine and better results with less influence of IPV. Conclusions: IPV of calcineurin inhibitors is only marginally associated with mid-term outcomes after heart transplant, particularly with the tacrolimus-based immunosuppression, although it could play a role in the most stable recipients (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)

Cancer Incidence in Heart Transplant Recipients With Previous Neoplasia History.

Neoplasm history increases morbidity and mortality after solid organ transplantation and has disqualified patients from transplantation. Studies are needed to identify factors to be considered when deciding on the suitability of a patient with previous tumor for heart transplantation. A retrospective epidemiological study was conducted in heart transplant (HT) recipients (Spanish Post-Heart Transplant Tumor Registry) comparing the epidemiological data, immu-nosuppressive treatments and incidence of post-HT tumors between patients with previous malignant noncardiac tumor and with no previous tumor (NPT). The impact of previous tumor (PT) on overall survival (OS) was also assessed. A total of 4561 patients, 77 PT and 4484 NPT, were evaluated. The NPT group had a higher proportion of men than the PT group (p < 0.001). The incidence of post-HT tumors was 1.8 times greater in the PT group (95% confidence interval [CI] 1.2-2.6; p < 0.001), mainly due to the increased risk in patients with a previous hematologic tumor (rate ratio 2.3, 95% CI 1.3-4.0, p < 0.004). OS during the 10-year posttransplant period was significantly lower in the PT than the NPT group (p = 0.048) but similar when the analysis was conducted after a first post-HT tumor was diagnosed. In conclusion, a history of PT increases the incidence of post-HT tumors and should be taken into account when considering a patient for HT.

Health-related quality of life, social support, and caregiver burden between six and 120 months after heart transplantation: a Spanish multicenter cross-sectional study.

A multicenter cross-sectional study was conducted to determine the current heart transplant (HTx) outcomes in Spain. Clinical and functional status, health-related quality of life (HRQoL), social support, and caregiver burden were analyzed in 303 adult transplant recipients (77.9% males) living with one functioning graft. Mean age at time of HTx (SD) was 56.4 (11.4) years, and the reason for transplantation in all patients was congestive heart failure. All patients had received a first heart transplant 6 (± 1), 12 (± 2), 36 (± 6), 60 (± 10), or 120 (± 20) months previously. Participants completed the Kansas City Cardiomyopathy Questionnaire (KCCQ), the EQ-5D, the Duke-UNC Functional Social Support Questionnaire, and the Zarit Caregiver Burden Scale. Reasonable HRQoL, social support, and caregiver burden levels were found at all time points, although a slight decrease in HRQoL was recorded at 120 months (p ≤ 0.033). Multivariate regression analyses showed that complications, comorbidities, and hospitalizations were associated with HRQoL (EQ-5D: 48.4% of explained variance, F4,164 = 38.46, p < 0.001; KCCQ overall summary score: 45.0%, F3,198 = 54.073, p < 0.001). Patient functional capabilities and complications affected caregiver burden (p < 0.05). In conclusion, HTx patients reported reasonable levels of HRQoL with low caregiver burden. Clinical variables related to these outcomes included functional status, complications, and number of admissions.

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.

Chronic renal dysfunction in maintenance heart transplant patients: the ICEBERG study.

Chronic renal dysfunction (CRD) is a major complication after heart transplantation. We sought to describe the renal function over time, to assess the risk factors associated with CRD development, and to evaluate the clinical attitudes on diagnosis and treatment of CRD. A retrospective, cross-sectional, multicenter study was conducted in 13 outpatient clinics in Spain. A total of 244 heart recipients who survived more than 2 years after transplantation were included. Post-transplantation follow-up was 7.7 years (range: 2-22 years). CRD was diagnosed in 32.4% of patients at a mean of 3.3 years after transplantation. Serum creatinine increased 0.1 ± 0.2 mg/dL per year in CRD group compared with 0.0 ± 0.2 mg/dL per year in non-CRD group (P = .003) and glomerular filtration rate decreased -1.5 ± 4.3 mL/min/1.73 m(2) per year in CRD group versus -0.1 ± 4.8 mL/min/1.73 m(2) per year in non-CRD group (P = .027). After CRD diagnosis, major changes in immunosuppression based on calcineurin inhibitors reduction were instituted in 46.8% of patients. Multivariate model identified recipient age (P < .0001), female sex (P = .0398), and time since transplant (P < .0001) as predictors of CRD. In conclusion, the prevalence of CRD in long-term heart recipient survivors was quite high. CRD was associated with nonmodifiable factors (age, gender, and time since transplant).

Use of mTOR inhibitors in chronic heart transplant recipients with renal failure: calcineurin-inhibitors conversion or minimization?

BACKGROUND: In the last decade, mTOR inhibitors (mTOR-is) have become the cornerstone of the calcineurin inhibitor (CNI)-reduced/free regimens aimed to the preservation of post-transplant renal function. We compared utility and safety of the total replacement of calcineurin inhibitors with a mTOR-i with a strategy based on calcineurin inhibitor minimization and concomitant use of m-TOR-i. METHODS: In a retrospective multi-center cohort of 394 maintenance cardiac recipients with renal failure (GFR<60 mL/min/1.73 m(2)), we compared 235 patients in whom CNI was replaced with a mTOR-i (sirolimus or everolimus) with 159 patients in whom mTOR-is were used to minimize CNIs. A propensity score analysis was carried out to balance between group differences. RESULTS: Overall, after a median time of 2 years from mTOR-i initiation, between group differences for the evolution of renal function were not observed. In a multivariate adjusted model, improvement of renal function was limited to patients with mTOR-i usage within 5years after transplantation, particularly with the conversion strategy, and in those patients who could maintain mTOR-i therapy. Significant differences between strategies were not found for mortality, infection and mTOR-i withdrawal due to drug-related adverse events. However, conversion group tended to have a higher acute rejection incidence than the minimization group (p=0.07). CONCLUSION: In terms of renal benefits, our results support an earlier use of mTOR-is, irrespective of the strategy. The selection of either a conversion or a CNI minimization protocol should be based on the clinical characteristics of the patients, particularly their rejection 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.

Lung cancer after heart transplantation: results from a large multicenter registry.

In this study we analyzed Spanish Post-Heart-Transplant Tumour Registry data for adult heart transplantation (HT) patients since 1984. Median post-HT follow-up of 4357 patients was 6.7 years. Lung cancer (mainly squamous cell or adenocarcinoma) was diagnosed in 102 (14.0% of patients developing cancers) a mean 6.4 years post-HT. Incidence increased with age at HT from 149 per 100 000 person-years among under-45s to 542 among over-64s; was 4.6 times greater among men than women; and was four times greater among pre-HT smokers (2169 patients) than nonsmokers (2188). The incidence rates in age-at-diagnosis groups with more than one case were significantly greater than GLOBOCAN 2002 estimates for the general Spanish population, and comparison with published data on smoking and lung cancer in the general population suggests that this increase was not due to a greater prevalence of smokers or former smokers among HT patients. Curative surgery, performed in 21 of the 28 operable cases, increased Kaplan-Meier 2-year survival to 70% versus 16% among inoperable patients.

Temporal trends in the use of proliferation signal inhibitors in maintenance heart transplantation: a Spanish multicenter study.

Proliferation signal inhibitors (PSI; sirolimus, everolimus) are being increasingly used in heart transplantation. We performed an observational, retrospective, multicenter study in 9 Spanish centers seeking to describe the clinical context in which a PSI was used among maintenance heart recipients and its evolution over time. We collected a cohort of 548 patients in whom a PSI was prescribed from October 2001 to March 2009. The group was divided into 3 time periods. The use of PSI steeply increased in the 2005-2006 period, remaining stable thereafter. There were no significant differences over time with regard to age, gender, or time from transplantation to the introduction of the PSI. Everolimus usage overtook sirolimus from 2005 on; currently, >90% of the subjects with PSI indications are prescribed everolimus. Compared with earlier periods, patients in the more recent period (October 2006-March 2009) showed less vascular graft disease and better basal renal function, irrespective of the primary indication for the PSI prescription. Also, skin cancer overtook solid cancer as the main type of neoplasm in patients for whom malignancy was the primary indication for the use of the PSI. The actuarial incidence of PSI withdrawal owing to adverse effects did not change significantly over time.

The prognosis of noncutaneous, nonlymphomatous malignancy after heart transplantation: data from the Spanish Post-Heart Transplant Tumour Registry.

INTRODUCTION: Malignancy is a major complication in the management of solid organ transplant patients. Skin cancers show a better prognosis than other neoplasms, but not all others are equal: Ideally, patient management must take into account the natural history of each type of cancer in relation to the transplanted organs. We sought to determine the prognosis of various groups of noncutaneous nonlymphomatous (NCNL) cancers after heart transplantation (HT). METHODS: We retrospectively analyzed the records of the Spanish Post-Heart-Transplant Tumour Registry, which collects data on posttransplant tumors in all patients who have undergone HT in Spain since 1984. Data were included in the study up to December 2008. We considered only the first NCNL post-HT tumors. RESULTS: Of 4359 patients, 375 developed an NCNL cancer. The most frequent were cancers of the lung (n=97; 25.9%); gastrointestinal tract (n=52; 13.9%); prostate gland (n=47; 12.5%; 14.0% of men), bladder (n=32; 8.5%), liver (n=14; 3.7%), and pharynx (n=14; 3.7%), as well as Kaposi's sarcoma (n=11; 2.9%). The corresponding Kaplan-Meier survival curves differed significantly (P<.0001; log-rank test), with respective survival rates of 47%, 72%, 91%, 73%, 36%, 64%, and 73% at 1 year versus 26%, 62%, 89%, 56%, 21%, 64%, and 73% at 2 years; and 15%, 51%, 77%, 42%, 21%, 64%, and 52% at 5 years post-diagnosis, respectively. CONCLUSION: Mortality among HT patients with post-HT NCNL solid organ cancers was highest for cancers of the liver or lung (79%-85% at 5 years), and lowest for prostate cancer (23%).

Steroid use in heart transplant patients in Spain in the current era: a multicenter survey.

OBJECTIVE: Steroid withdrawal (SW) from maintenance therapy in heart transplant patients is still a controversial subject. We designed a questionnaire to ascertain the attitudes and procedures of a number of Spanish heart transplant units (16) regarding the use/withdrawal of steroids as part of the immunosuppressive maintenance therapy. MATERIALS AND METHODS: We sent an 11-item questionnaire to the clinical director in charge of each unit. The questionnaire was completed and returned by 14 units. RESULTS: In 21.5% of the centers SW was performed in all patients, while 78.5% of the centers only performed SW in selected patients. In 57% of units SW was performed at 12 months posttransplantation and between 6 and 12 months in the rest. Fewer than 20% of patients were steroid-free in 46% of units while in 23% of units this proportion was >50%. In 11 units, the minimum prednisone dose administered was

Outcomes of heart transplantation for cardiac amyloidosis: subanalysis of the spanish registry for heart transplantation.

Amyloidosis (Am), a systemic disease, has poor prognosis because of organ damage produced by protein deposition in the extracellular space. Although heart transplantation (HTx) is possible, donor availability concerns and high mortality make this approach controversial. The Spanish Registry for Heart Transplantation includes 25 Am patients (54 +/- 9 years): 13 with AL type, 2 with AA and 10 with TTR mutation. Fifteen patients (60%) died during follow-up (4.9 +/- 1.3 years): 9 AL-Am patients, both AA-Am patients and 4 with TTR-Am. HTx survival for Am patients was similar to patients without Am at 1 month but significantly worse at 5 years: 46% versus 78% (p < 0.02). Of 10 AL-Am patients undergoing successful HTx, 4 died of systemic Am. Stem cell transplantation was performed in 3 (1 died of acute rejection). Five of 10 patients with TTR-Am underwent liver transplant; 4 remained alive at the last follow-up. Findings include poor outcome for AL-Am patients despite HTx and better survival for TTR-Am patients if HTx is associated with liver transplantation. Given the shortage of donors and poor outcome for Am patients, we would recommend that HTx be reserved for patients without or with mild systemic Am and be supplemented by additional therapies as indicated.

Gastrointestinal complications in heart transplant patients: MITOS study.

INTRODUCTION: The most frequent immunosuppressive treatment complications in solid organ transplant recipients are gastrointestinal (GI) disorders. MATERIALS AND METHODS: An observational, cross-sectional study to evaluate the prevalence and management of GI complications in transplanted patients was conducted via a written questionnaire given to doctors at their practice. RESULTS: This study included 1788 patients; 181 corresponded to heart transplant recipients. The mean age for the heart transplant patients was 58.7 +/- 11.8 years. The mean time from the transplantation was 5.2 +/- 4.4 years. GI complications were seen in 38.7% of cases. Regarding the clinical management, in 72.9% of cases patients with GI complications received pharmacologic treatment, 86.3% with gastric protectors, 32.8% reduced the dose of some drug, 8.1% interrupted the drug temporarily, and 10.9% discontinued the drug permanently. The drug that was always discontinued was mycophenolate mofetil (MMF), and in 85.7% of cases in which the dose of an immunosuppressive drug was reduced, the reduced drug was also MMF. CONCLUSIONS: Almost 40% of heart transplant recipients suffered GI complications which affected daily activities in most cases. The most used strategy to manage these complications was based on a treatment with gastric protectors together with dose reduction and/or partial or definitive MMF discontinuation.

Sirolimus as an alternative to anticalcineurin therapy in heart transplantation: experience of a single center.

We report a series of 26 heart transplant recipients with renal impairment in which sirolimus was used as the basic immunosuppresive drug (without associated calcineurin inhibitors) to avoid further nephrotoxicity. Sirolimus (trough levels 10 to 12 ng/mL, average daily dose 3 mg) was used in two settings: de novo in 7 patients with significant preexistent renal impairment and as a chronic conversion in 19 stable patients with established renal failure (creatinine level >2 mg/dL). In all de novo patients (n = 7), the renal function significantly improved. Creatinine fell from 2.95 +/- 0.9 mg/dL to 1.41 +/- 0.4 mg/dL at follow-up (P = .0017). One patient died suddenly of a massive pulmonary embolism. Only one patient experienced histologic but reversible rejection. In one patient, anemia and diarrhea prompted sirolimus withdrawal. Five patients had infectious episodes: three bacterial pneumonias, one mediastinitis, and two CMV infections. In the chronic conversion group (n = 19), the improvement was mostly limited to patients with moderate renal failure (creatinine < or =2.5 mg/dL) in which creatinine fell from 2.24 +/- 0.2 to 1.9 +/- 0.27 mg/dL, P = .009). When basal creatinine was over 2.5 mg/dL, only one third of the patients improved after conversion. Two patients died: terminal renal failure and cerebrovascular accident. There were no clinical episodes of rejection. Secondary effects prompted the discontinuation of sirolimus in five patients: two definite and one possible interstitial pneumonitis and two cases of anemia). The symptoms resolved after sirolimus withdrawal. Six patients had infection: four pneumonias, one sepsis, and one cutaneous abscess. Sirolimus is an interesting alternative to calcineurin inhibitors in selected patients with renal impairment. It prevents renal failure in de novo recipients at high risk of catastrophic renal damage and ameliorates renal dysfunction in chronic patients with moderate renal dysfunction. Given the high incidence of secondary effects, the adequate dosage and the secondary effects profile needs further study.