Impacto pronóstico de la enfermedad pulmonar obstructiva crónica y el asma bronquial en pacientes con insuficiencia cardiaca / Prognostic impact of chronic obstructive pulmonary disease and bronchial asthma in patients with heart failure

Propósito Analizar el impacto de la enfermedad pulmonar obstructiva crónica (EPOC) y el asma bronquial sobre el manejo terapéutico y el pronóstico de los pacientes con insuficiencia cardiaca (IC). Métodos Análisis de la información contenida en un registro clínico de pacientes remitidos a una unidad especializada de IC entre enero de 2010 y junio de 2022. Se compararon su perfil clínico, el tratamiento y el pronóstico en base a la presencia de EPOC o asma bronquial. El análisis de supervivencia se realizó mediante los métodos de Kaplan-Meier y Cox. La mediana de seguimiento fue de 1.493 días. Resultados Se estudiaron 2.577 pacientes, de los cuales 251 (9,7%) presentaban EPOC y 96 (3,7%), asma bronquial. Observamos diferencias significativas entre los tres grupos con respecto a la prescripción de betabloqueantes (EPOC=89,6%; asma=87,5%; no broncopatía=94,1%; p=0,002) e inhibidores del cotransportador de sodio-glucosa tipo2 (EPOC=35,1%; asma=50%; no broncopatía=38,3%; p=0,036). Además, los pacientes con patología bronquial recibieron con menor frecuencia un desfibrilador (EPOC=20,3%; asma=20,8%; no broncopatía=29%; p=0,004). La presencia de EPOC se asoció de forma independiente con mayor riesgo de muerte por cualquier causa (HR=1,64; IC95%: 1,33-2,02), muerte u hospitalización por IC (HR=1,47; IC95%: 1,22-1,76) y muerte cardiovascular o trasplante cardiaco (HR=1,39; IC95%: 1,08-1,79) en comparación con la ausencia de broncopatía. La presencia de asma bronquial no se asoció a un impacto significativo sobre los desenlaces analizados. Conclusiones La EPOC, pero no el asma bronquial, es un factor pronóstico adverso e independiente en pacientes con IC. (AU)

Purpose To analyze the impact of chronic obstructive pulmonary disease (COPD) and bronchial asthma on therapeutic management and prognosis of patients with heart failure (HF). Methods Analysis of the information collected in a clinical registry of patients referred to a specialized HF unit from January-2010 to June-2012. Clinical profile, treatment and prognosis of patients was evaluated, according to the presence of COPD or asthma. Survival analyses were conducted by means of Kaplan-Meier and Cox's methods. Median follow-up was 1493 days. Results We studied 2577 patients, of which 251 (9.7%) presented COPD and 96 (3.7%) bronchial asthma. Significant differences among study groups were observed regarding to the prescription of beta-blockers (COPD=89.6%; asthma=87.5%; no bronchopathy=94.1%; P=.002) and SGLT2 inhibitors (COPD=35.1%; asthma=50%; no bronchopathy=38.3%; P=.036). Also, patients with bronchial disease received less frequently a defibrillator (COPD=20.3%; asthma=20.8%; no broncopathy=29%; P=.004). COPD was independently associated with increased risk of all-cause mortality (HR=1.64; 95%CI: 1.33-2.02), all-cause death or HF admission (HR=1.47; 95%CI: 1.22-1.76) and cardiovascular death or heart transplantation (HR=1.39; 95%CI: 1.08-1.79) as compared with patients with no bronchopathy. Bronchial asthma was not significantly associated with increased risk of adverse outcomes. Conclusions COPD, but not asthma, is an adverse independent prognostic factor in patients with HF. (AU)

Prognostic impact of chronic obstructive pulmonary disease and bronchial asthma in patients with heart failure.

PURPOSE: To analyze the impact of chronic obstructive pulmonary disease (COPD) and bronchial asthma on therapeutic management and prognosis of patients with heart failure (HF). METHODS: Analysis of the information collected in a clinical registry of patients referred to a specialized HF unit from January-2010 to June-2012. Clinical profile, treatment and prognosis of patients was evaluated, according to the presence of COPD or asthma. Survival analyses were conducted by means of Kaplan-Meier and Cox's methods. Median follow-up was 1493 days. RESULTS: We studied 2577 patients, of which 251 (9.7%) presented COPD and 96 (3.7%) bronchial asthma. Significant differences among study groups were observed regarding to the prescription of beta-blockers (COPD=89.6%; asthma=87.5%; no bronchopathy=94.1%; p=0.002) and SGLT2 inhibitors (COPD=35.1%; asthma=50%; no bronchopathy=38.3%; p=0.036). Also, patients with bronchial disease received less frequently a defibrillator (COPD=20.3%; asthma=20.8%; no broncopathy=29%; p=0.004). COPD was independently associated with increased risk of all-cause mortality (HR=1.64; 95% CI 1.33-2.02), all-cause death or HF admission (HR=1.47; 95% CI 1.22-1.76) and cardiovascular death or heart transplantation (HR=1.39; 95% CI 1.08-1.79) as compared with patients with no bronchopathy. Bronchial asthma was not significantly associated with increased risk of adverse outcomes. CONCLUSIONS: COPD, but not asthma, is an adverse independent prognostic factor in patients with HF.

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)

Clinical profile and causes of death according to ejection fraction in patients with heart failure cared for in a specialized Cardiology unit.

BACKGROUND AND OBJECTIVE: Patients with heart failure are classified into three phenotypes based on left ventricular ejection fraction. This work aimed to compare the clinical profile, treatment, prognosis, and causes of death of patients with heart failure and reduced (<40%, HF-rEF), preserved (≥50%, HF-pEF), or mid-range (40-49%, HF-mrEF) left ventricular ejection fraction. METHODS: An analysis was conducted on the clinical data included in a prospective registry of patients with heart failure who were referred to a specific Cardiology unit from 2010 to 2019. RESULTS: A total of 1404 patients with HF-rEF, 239 patients with HF-mrEF, and 266 patients with HF-pEF were analyzed. Significant differences were observed among the groups in regard to several clinical characteristics and the frequency of prescription of neurohormonal blocking drugs. A multivariate Cox regression revealed an increased risk of all-cause mortality in patients with HF-pEF (hazard ratio 1.36; 95% confidence interval 1.03-1.80; p = 0.028) and patients with HF-mrEF (hazard ratio 1.36; 95% confidence interval 1.03-1.78; p = 0.029) as compared to patients with HF-rEF. Heart failure was the most frequent cause of death in the three subgroups. A higher relative weight of sudden death as a cause of death was observed among patients with HF-rEF while the relative weight of non-cardiovascular causes of death was higher among patients with HF-pEF and HF-mrEF. CONCLUSIONS: This study confirms the existence of significant differences among patients with HF-rEF, HF-mrEF, and HF-pEF with regard to their clinical profile, therapeutic management, prognosis, and causes of death.

Perfil clínico y causas de muerte de los pacientes con insuficiencia cardíaca atendidos en una unidad especializada de Cardiología según su fracción de eyección / Clinical profile and causes of death according to ejection fraction in patients with heart failure cared for in a specialized Cardiology unit

Antecedente y objetivo: Los pacientes con insuficiencia cardíaca se caracterizan en 3 fenotipos en función de su fracción de eyección ventricular izquierda. El propósito de este estudio fue comparar el perfil clínico, el tratamiento, el pronóstico y las causas de muerte de los pacientes con insuficiencia cardíaca y fracción de eyección ventricular izquierda reducida (<40%, IC-FEr), preservada (≥50%, IC-FEp) o en rango medio (40-49%, IC-FErm). Metodología: Análisis de la información clínica recogida en un registro prospectivo de pacientes con insuficiencia cardíaca remitidos a una consulta monográfica de Cardiología entre 2010 y 2019. Resultados: Se estudiaron 1.404 pacientes con IC-FEr, 239 pacientes con IC-FErm y 266 pacientes con IC-FEp. Se observaron diferencias significativas entre los 3 grupos en relación con diversas características clínicas, y en cuanto a la tasa de prescripción de fármacos moduladores de la respuesta neurohormonal. La regresión de Cox multivariante reveló un incremento del riesgo de muerte por cualquier causa en los pacientes con IC-FEp (hazard-ratio 1,36; intervalo de confianza al 95% 1,03-1,80; p=0,028) e IC-FErm (hazard-ratio 1,36; intervalo de confianza al 95% 1,03-1,78; p=0,029) en comparación con los pacientes con IC-FEr. La insuficiencia cardíaca fue la causa más frecuente de muerte en los 3 grupos; se observó un mayor peso relativo de la muerte súbita en los pacientes con IC-FEr, mientras que las causas no cardiovasculares de muerte tuvieron un peso relativo mayor en los pacientes con IC-FEp e IC-FErm. Conclusiones: El estudio confirma la existencia de diferencias significativas en el perfil clínico, manejo terapéutico, pronóstico y causas de muerte de los pacientes con IC-FEr, IC-FErm e IC-FEp (AU)

Background and objective: Patients with heart failure are classified into three phenotypes based on left ventricular ejection fraction. This work aimed to compare the clinical profile, treatment, prognosis, and causes of death of patients with heart failure and reduced (<40%, HF-rEF), preserved (≥50%, HF-pEF), or mid-range (40–49%, HF-mrEF) left ventricular ejection fraction. Methods: An analysis was conducted on the clinical data included in a prospective registry of patients with heart failure who were referred to a specific Cardiology unit from 2010 to 2019. Results: A total of 1,404 patients with HF-rEF, 239 patients with HF-mrEF, and 266 patients with HF-pEF were analyzed. Significant differences were observed among the groups in regard to several clinical characteristics and the frequency of prescription of neurohormonal blocking drugs. A multivariate Cox regression revealed an increased risk of all-cause mortality in patients with HF-pEF (hazard ratio 1.36; 95% confidence interval 1.03-1.80; p=0.028) and patients with HF-mrEF (hazard ratio 1.36; 95% confidence interval 1.03–1.78; p=0.029) as compared to patients with HF-rEF. Heart failure was the most frequent cause of death in the three subgroups. A higher relative weight of sudden death as a cause of death was observed among patients with HF-rEF while the relative weight of non-cardiovascular causes of death was higher among patients with HF-pEF and HF-mrEF. Conclusions: This study confirms the existence of significant differences among patients with HF-rEF, HF-mrEF, and HF-pEF with regard to their clinical profile, therapeutic management, prognosis, and causes of death (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)

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)

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.

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.

Clinical characteristics and long-term outcomes of patients undergoing combined heart-kidney transplantation: a single-center experience.

BACKGROUND: The purpose of the study was to describe clinical characteristics and long-term survival of patients undergoing combined heart-kidney transplant in a single center. METHODS: We conducted a retrospective analysis of 22 consecutive patients who underwent combined heart-kidney transplant at our institution between 1995 and 2013. Long-term outcomes were analyzed by means of the Kaplan-Meier method. RESULTS: Four patients underwent re-do transplant (2 cardiac re-transplants, 1 kidney re-transplant, and 1 combined heart-kidney re-transplant). Most frequent underlying cardiac conditions were coronary artery disease (54%), dilated cardiomyopathy (23%), and chronic rejection of a previous heart graft (18%). Known causes of chronic renal dysfunction were nephroangioesclerosis (23%), drug-related toxicity (14%), and Wegener granulomatosis (5%). Non-specified chronic renal dysfunction was present in 50% patients. In-hospital postoperative mortality rate was 5 of 22 (23%). Causes of early death were directly related to kidney transplant surgery in 4 of 5 (80%) patients. Among the remaining 17 patients who surmounted the postoperative period, long-term survival rates 1 year, 5 years, and 10 years after HKT were 88%, 82%, and 65%, respectively. Over a mean follow-up of 6.7 ± 6.4 years, cumulative incidences of cytomegalovirus infection, coronary allograft vasculopathy, malignancy, and acute cardiac graft rejection were 41%, 6%, 24%, and 41%, respectively. There was no episode of acute renal graft rejection. At the end of follow-up, all survivors (n = 11) were in functional New York Heart Association class I. Mean creatinine serum level was 1.68 mg/dL. CONCLUSIONS: In our experience, combined heart-kidney transplant is a feasible therapeutic option that yielded favorable long-term outcomes, with a low cumulative incidence of cardiac graft dysfunction. These results were obtained at the expense of a significant risk of early postoperative mortality, which was mainly related to complications of kidney transplant surgery.

Sirolimus conversion after heart transplant: risk factors for acute rejection and predictors of renal function response.

In a randomized, comparative study of cardiac transplant patients with mild-to-moderate renal insufficiency, conversion from calcineurin inhibitors (CNIs) to sirolimus improved renal function at 1 year versus continuing CNIs, with an attendant risk of biopsy-confirmed acute rejection (BCAR). Post hoc analyses were conducted to identify predictors of BCAR and GFR improvement associated with conversion. Patients with proteinuria >500 mg/day were excluded. Univariate and multivariate regression analyses tested 13 parameters for BCAR and six for GFR improvement. In 57 sirolimus-treated patients, mean daily mycophenolate mofetil (MMF) dose was lower in those with versus without BCAR (1000 vs. 1420 mg; p = 0.014). Receiver operating characteristic analysis identified MMF dose ≤1000 mg/day as the optimal cutoff to predict BCAR. Multivariate analysis confirmed low MMF dose (odds ratio: 9.94; p = 0.007) and non-white race (odds ratio: 15.3; p = 0.06) were independently associated with BCAR. GFR improvement was evaluated in intent-to-treat patients (n = 116). Significant interaction was detected between treatment effect and preexisting diabetes status (univariate p = 0.077; multivariate p = 0.022), indicating greater beneficial effect of sirolimus in those without preexisting diabetes. These findings suggest that sirolimus is more effective in improving GFR in patients without preexisting diabetes, and adequate MMF doses are needed for sirolimus conversion.

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.

Mitochondrial DNA haplogroup H as a risk factor for idiopathic dilated cardiomyopathy in Spanish population.

Idiopathic dilated cardiomyopathy (IDC) is a structural heart disease with strong genetic background. The different single nucleotide polymorphisms (SNPs) that constitute mitochondrial haplogroups could play an important role in IDC progression. The aim of this study was to test frequencies of mitochondrial haplogroups in healthy controls (n=422) and IDC patients (n=304) of a Caucasian Spanish population. To achieve this, ten major European haplogroups were identified. Frequencies and Odds Ratios for the association between IDC and haplogroups were calculated in both groups. We found that compared to healthy controls, the prevalence of haplogroup H was significantly higher in IDC patients (40.0% vs 50.7%, p-value=0.040).

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.

Indoleamine, 2-3 dioxygenase activity could be an early marker of graft rejection in heart transplantation.

BACKGROUND: The indoleamine, 2-3 dioxygenase (IDO) is an inducible intracellular enzyme with immunosuppressive effects mainly on lymphocyte populations. It has been postulated that indirect determination of IDO serum activity may be a marker of renal graft rejection, but its potential usefulness in heart transplantation (HT) is unknown. METHODS: This longitudinal study included 98 HT patients (83% males) who survived ≥1 year. Mean age was 54.14 ± 11.57 years. Serum IDO activity was analyzed one month after HT by means of high performance liquid chromatography and correlated with the cumulative incidence of acute rejection (AR) during one-year follow-up. AR was defined as biopsy-proven ≥ ISHLT grade 2R rejection or empirically treated non-biopsy-proven rejection. The study sample was divided into two groups: AR group (n = 51), including patients who experienced at least one AR episode during the first year after HT; No-AR group (N = 47), including the remaining patients. RESULTS: Mean serum IDO activity one month after HT was significantly higher (P = .021) in the AR group (3.32 ± 1.56) than in the no-AR group (2.62 ± 1.35). No significant association between serum IDO activity and gender (male: 3.1 ± 1.56, women: 2.43 ± 0.99, P = .092), recipient age (r = -.07, P = .943) or donor age (r = 0.108, P = 0.293) was observed. By means of binary logistic regression, an odds ratio of 1.4 [CI 95%: 1.033-1.876, P = .03] per unit increase of act-IDO was estimated, with no significant modification upon forced adjustment for age and sex. Mean glomerular filtration rate 1 month after HT was 67.01 ± 28.51 mL/min/m(2). No significant correlation between this parameter and serum IDO activity was observed (r = .160, P = .117). CONCLUSIONS: Our study suggests that serum IDO activity one month after HT might be associated with a higher risk of AR during one-year follow-up. This association seems to be independent of recipient gender, age or renal function.

Percutaneous coronary interventions and bypass surgery in patients with cardiac allograft vasculopathy: a single-center experience.

INTRODUCTION: Cardiac allograft vasculopathy (CAV) remains a major impediment to long-term survival after heart transplantation (HT). Limited data exist regarding the impact of coronary revascularization in these patients. OBJECTIVE: To evaluate the outcomes of revascularization procedures in patients with CAV compared with patients who did not undergo revascularization. METHODS: Retrospective analysis of 249 patients who underwent HT at our center between June 1998 and December 2009 and who were examined by coronary angiography after HT. We included patients with moderate or severe CAV according to the International Society for Heart and Lung Transplantation (ISHLT) nomenclature to evaluated outcomes after revascularization or diagnostic angiography. Major adverse cardiovascular events (MACE) comprised death, acute coronary syndrome, coronary revascularization, admission because of heart failure not due to an acute rejection episode, and cardiac retransplantation. RESULTS: Moderate or severe CAV was detected in 43 patients. Twelve (27.9%) underwent coronary revascularization: eight percutaneous interventions and four bypass surgeries. Indications for revascularization were symptomatic ischemia or noninvasive evidence of ischemia (n = 6, 14.0%) or high-risk asymptomatic CAV (n = 6; 14.0%), namely, lesions located in the left main or proximal anterior descending arteries or multivessel disease with left ventricular dysfunction. The remaining 31 (72.1%), who did not undergo revascularization showed an absence of ischemia during exercise echocardiography (n = 11; 25.6%) or diffuse disease not amenable to revascularization (n = 20; 46.5%). During a mean follow-up of 3.0 ± 2.4 years, MACE occurred in three revascularized patients (25.0%), in one with absence of stress-induced ischemia (9.1%) and in 13 with nonrevascularizable disease (65%; P = .012). CONCLUSIONS: Revascularization procedures were effective in HT patients with evidence of ischemia or high-risk CAV. Patients with absence of stress-induced ischemia have a good prognosis without revascularization. On the other hand, diffuse nonrevascularizable CAV is associated with a poor prognosis.