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[Abstract] Introduction and objectives: Mitochondrial pyruvate carrier (MPC) mediates the entry of pyruvate into mitochondria, determining whether pyruvate is incorporated into the Krebs cycle or metabolized in the cytosol. In heart failure (HF), a large amount of pyruvate is metabolized to lactate in the cytosol rather than being oxidized inside the mitochondria. Thus, MPC activity or expression might play a key role in the fate of pyruvate during HF. The purpose of this work was to study the levels of the two subunits of this carrier, named MPC1 and MPC2, in human hearts with HF of different etiologies. Methods: Protein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA. Results: Significant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group. Conclusion: Decreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features.

[Abstract] The first-generation Molecular Microscope (MMDx) system for heart transplant endomyocardial biopsies used expression of rejection-associated transcripts (RATs) to diagnose not only T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) but also acute injury. However, the ideal system should detect rejection without being influenced by injury, to permit analysis of the relationship between rejection and parenchymal injury. To achieve this, we developed a new rejection classification in an expanded cohort of 3230 biopsies: 1641 from INTERHEART (ClinicalTrials.gov NCT02670408), plus 1589 service biopsies added to improve the power of the machine learning algorithms. The new system used 6 rejection classifiers instead of RATs and generated 7 rejection archetypes: No rejection, 48%; Minor, 24%; TCMR1, 2.3%; TCMR2, 2.7%; TCMR/mixed, 2.7%; early-stage ABMR, 3.9%; and fully developed ABMR, 16%. Using rejection classifiers eliminated cross-reactions with acute injury, permitting separate assessment of rejection and injury. TCMR was associated with severe-recent injury and late atrophy-fibrosis and rarely had normal parenchyma. ABMR was better tolerated, seldom producing severe injury, but in later biopsies was often associated with atrophy-fibrosis, indicating long-term risk. Graft survival and left ventricular ejection fraction were reduced not only in hearts with TCMR but also in hearts with severe-recent injury and atrophy-fibrosis, even without rejection.

[Resumen] Antecedentes y objetivo. La hiperpotasemia (HK) es una alteración electrolítica en la concentración de iones potasio (K+), cuyo riesgo aumenta en pacientes con enfermedad renal crónica (ERC) o insuficiencia cardiaca (IC) y/o en pacientes en tratamiento con inhibidores del sistema renina-angiotensina-aldosterona (iSRAA). Los nuevos quelantes orales de K+ ofrecen un tratamiento seguro y eficaz para mantener la normopotasemia en estos pacientes. El objetivo del análisis es estimar el coste-efectividad del ciclosilicato de sodio y zirconio (CSZ) para el tratamiento de la HK crónica en pacientes con ERC o IC vs. tratamiento estándar (poliestireno sulfonato cálcico y modificaciones del estilo de vida) desde la perspectiva del Sistema Nacional de Salud (SNS) español. Materiales y métodos. Se utilizaron dos modelos de microsimulación que reflejan la historia natural de la ERC y de la IC. En ambos modelos se realizó una simulación de forma individual de los niveles de K+. Con base en la eficacia (reducción de los niveles de K+), la calidad de vida de los pacientes (utilidades según estado de salud, y disutilidades de los eventos derivados de cada patología y los eventos adversos [EA] del tratamiento) y a los costes contemplados (coste del tratamiento para la HK, del tratamiento con iSRAA y su modificación, de los estados de salud, del manejo de los eventos derivados de cada patología, de los episodios de HK, y de los EA del tratamiento) (€, 2022), se obtuvieron resultados de beneficio clínico (años de vida ajustados por calidad [AVAC]) y costes. Se empleó un horizonte temporal de toda la vida del paciente y se aplicó una tasa de descuento del 3% para costes y resultados. Resultados. El CSZ resulta una opción más efectiva en ambas patologías, con una diferencia de AVAC de 0,476 en ERC, y de 0,978 en IC vs. tratamiento estándar, y supone un coste incremental de 3.616 € y 14.749 €, respectivamente, obteniéndose un ratio coste-utilidad incremental (RCUI) de 7.605 €/AVA, [Abstract] Background and objective. Hyperkalemia (HK) is an electrolyte disturbance in the concentration of potassium ions (K+), whose risk increases in patients with chronic kidney disease (CKD) or heart failure (HF) and/or in patients being treated with renin-angiotensin-aldosterone system inhibitors (RAASi). The new oral K+ chelators offer a safe and effective treatment to maintain normokalemia in these patients. The objective of the analysis is to estimate the cost-effectiveness of sodium zirconium cyclosilicate (SZC) for the treatment of chronic HK in patients with CKD or HF versus standard treatment (calcium polystyrene sulfonate and lifestyle modifications) from the perspective of the Spanish National Health System. Materials and methods. Two microsimulation models reflecting the natural history of CKD and HF were used. In both models, K+ levels were simulated individually. Based on efficacy (reduction of K+ levels), quality of life of patients (utilities according to health states, and disutilities of events derived from each pathology and adverse events [AEs] of treatment) and costs considered (cost of treatment for HK, of RAASi treatment and its modification, health states, management of events derived from each pathology, HK episodes, and AEs treatment) (€, 2022), clinical benefit (quality-adjusted life years [QALYs]) and cost results were obtained. A time horizon of the patient's lifetime was used and a discount rate of 3% was applied for costs and outcomes. Results. SZC is a more effective option in both pathologies, with a difference in QALYs of 0.476 in CKD and 0.978 in HF compared to standard treatment, and it represents an incremental cost of € 3,616 and € 14,749, respectively, obtaining an incremental cost-utility ratio of € 7,605 /QALY in CKD and € 15,078 /QALY in HF. Conclusions. SZC is a cost-effective alternative for the treatment of HK in patients with CKD or HF, taking into account the reference efficiency values commonly used in Spain.

[Resumen] Introducción. Una causa frecuente de hospitalización en pacientes con insuficiencia cardiaca es congestión refractaria a diuréticos orales y se trata con furosemida intravenosa. La administración de furosemida subcutánea puede ser una alternativa. Objetivo: analizar nuestra experiencia inicial con administración de furosemida subcutánea mediante infusor elastomérico de 7 días. Material y métodos. Estudio retrospectivo unicéntrico. Criterios inclusión: 1) congestión refractaria sin bajo gasto, 2) consentimiento informado. La indicación la realiza el cardiólogo. Dosis fija furosemida subcutánea: 120 mg/día, el infusor lo prepara el servicio de Farmacia y el implante, seguimiento y educación específica lo realiza la enfermera. El paciente controla diariamente diuresis y autocontrol habitual de insuficiencia cardiaca. Cada 48h, control analítico y telemático. Las variables cuantitativas fueron analizadas mediante test de Wilcoxon. Resultados. Desde abril de 2020 se realizaron 20 tratamientos en 15 pacientes. Tres pacientes, requirieron > 1 tratamiento. Tiempo mediano de tratamiento: 7 días (RIC 5-13). Hubo descenso significativo del peso (descenso mediano 2,9 Kg, RIC 0,45-4,45, p=0,002), sin deterioro renal (creatinina mediana inicial 1,46 vs creatinina final 1,58 mg/dL, p=0,233) ni hipopotasemia (potasio inicial mediano 4,3 vs potasio final 4 mEq/L, p=0,640). Tras seguimiento mediano de 171 días, el 73% se mantuvo libre de ingreso, tres pacientes fallecieron, uno fue trasplantado y dos tuvieron efectos adversos leves. Conclusión. En esta experiencia preliminar, furosemida subcutánea mediante infusor elastomérico de 7 días consigue mejoría clínica y de peso en situaciones de insuficiencia cardiaca avanzada con congestión refractaria, evitando hospitalizaciones en > del 70% de los episodios de un modo seguro., [Abstract] Introduction. A frequent cause of hospitalization in patients with heart failure is congestion refractory to oral diuretics and is treated with intravenous furosemide. Subcutaneous furosemide administration may be an alternative. Objective: To analyse our initial experience with the use of subcutaneous furosemide administration by elastomeric infuser for 7 days.Material and methods. Retrospective single-centre study. Inclusion criteria: 1) Refractory congestion without low output; and 2) informed consent. The indication is made by the cardiologist. Fixed dose subcutaneous furosemide (120 mg/day) was administered; the infuser was prepared by hospital pharmacy and the implantation, follow-up and specific education was carried out by the nurse. The patient controls daily diuresis, as well as routine self-control of HF. Every 48 hours, analytical and telematic control was performed. The quantitative variables were analysed using the Wilcoxon test.Results. Since April 2020, 20 treatments were performed in 15 patients. Three patients required >1 treatment. Median treatment time was: 7 days (IQR 5-13). There was a significant weight reduction (median weight loss 2.9 kg, IQR 0.45–4.45, p=0.002), without renal deterioration (basal median Cr 1.46 vs. final Cr 1.58 mg/dL; p=0.233) or hypokalaemia (basal median K+ 4.3 vs. final K+ 4 mEq/L; p=0.640). After a median follow-up of 171 days, 73% of patients remained free of admission, three patients died, one was transplanted, and two had mild adverse effects.Conclusion. In this preliminary experience, subcutaneous furosemide administration by elastomeric infuser for 7 days achieved clinical and weight improvement in advanced heart failure patients with refractory congestion, safely avoiding hospitalizations in >70% of episodes.

[Abstract] Aims: To evaluate the effect of long-term tafamidis treatment on health-related quality of life (HRQoL) in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) enrolled in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and long-term extension (LTE) study. Methods and results: We examined change from baseline in Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS) and clinical summary (KCCQ-CS) scores in patients who received tafamidis meglumine 80 mg for 30 months in ATTR-ACT and tafamidis (meglumine 80 mg or bioequivalent free acid 61 mg) for 30 months in the LTE study, and in patients who received placebo for 30 months in ATTR-ACT and tafamidis for 30 months in the LTE study. In ATTR-ACT, 176 and 177 patients were randomized to tafamidis 80 mg and placebo, respectively. Patients who continuously received tafamidis had a 6- to 7-point reduction in least squares (LS) mean (standard error) KCCQ-OS and KCCQ-CS scores at month 30 (-6.25 [1.53] and -7.48 [1.39]), with little or no further decline over the next 30 months (-5.92 [1.77] and -9.21 [1.88] at month 60). Patients who received placebo in ATTR-ACT had a 20-point reduction in LS mean KCCQ-OS and KCCQ-CS scores at month 30 (-19.60 [1.94] and -19.90 [2.01]), but the decline slowed after initiating tafamidis (-24.70 [3.04] and -25.30 [3.36] at month 60). Conclusion: Tafamidis reduced HRQoL decline in patients with ATTR-CM. Patients continuously treated with tafamidis for 60 months demonstrated stabilized HRQoL. In patients who initially received placebo in ATTR-ACT, tafamidis reduced the decline in HRQoL during the LTE study.

Introduction. The clinical follow up of heart transplant patients is complex and requires the nurse to transmit knowledge according to needs to promote self-care and therapeutic adherence. The objective was to evaluate the nurse educational intervention in transplanted patients.Methodology. An observational-descriptive-transversal study was performed of patients who received heart transplants in 2019 and 2020 (n=41) at the Advanced Heart Failure Unit of the University Hospital of A Coruña using knowledge, assessment, and adherence questionnaires (BAASIS).Results. Forty-one patients participated with a mean age of 60.5 (±6.9), 80.5% were male. According to priority, 53.7% were elective. The 15 knowledge questions were answered correctly by 36.8%. The questions with more failures were those related to rejection symptoms.All patients considered the information received to be useful and 92.7% reported that it helped them improve their anxiety and fear.Three immunosuppressive drugs were taken by 87.2%: Tacrolimus 100%, of which 84.6% in a single morning dose, prednisone 97.4%, mycophenolate mofetil 79.5%, and everolimus 10.3%. No patient fully stopped taking immunosuppressants in the last year. During the last month, two patients forgot or changed the prescribed dose once.The maximum score was achieved by 69.2% of patients for their behavior regarding taking immunosuppressive drugs.Conclusions. The results obtained show that during the first year after heart transplantation, patients maintain an acceptable level of knowledge, good adherence to immunosuppressants, and consider the nurse educational intervention useful., Introducción. El seguimiento clínico de pacientes trasplantados de corazón es complejo y requiere que la enfermera trasmita conocimientos según necesidades para fomentar el autocuidado y adherencia terapéutica. El objetivo fue evaluar la intervención educativa enfermera en pacientes trasplantados.Metodología. Se realizó un estudio observacional-descriptivo-transversal de los pacientes trasplantados de corazón en 2019 y 2020 (n=41) en la Unidad de Insuficiencia Cardiaca Avanzada del Hospital Universitario de A Coruña, a través de cuestionarios de conocimientos, evaluación y adherencia BAASIS©.Resultados. Participaron 41 pacientes con una edad media de 60,5 (±6,9), hombres el 80,5%. Según prioridad fueron 53,7% electivo. Respondieron correctamente a las 15 preguntas de conocimientos el 36,8%. Las preguntas con más errores fueron las relativas a los síntomas del rechazo.Todos los pacientes consideraron la información recibida útil y un 92,7% refirieron que les ayudó a mejorar la ansiedad y el miedo.El 87,2% tomaron tres fármacos inmunosupresores: tacrolimus 100%, de los cuales el 84,6% en una sola toma por la mañana, prednisona 97,4%, micofenolato de mofetilo 79,5% y everolimus 10,3%. Ningún paciente dejó de tomar los inmunosupresores por completo en el último año. Durante el último mes olvidaron o modificaron una vez la dosis pautada dos pacientes.El 69,2% de los pacientes puntuaron con el máximo su conducta sobre la toma de medicamentos inmunosupresores. Conclusiones. Los resultados obtenidos muestran que los pacientes mantienen, durante el primer año del trasplante de corazón, un nivel de conocimientos aceptable, buena adherencia a los inmunosupresores y consideran útil la intervención educativa-enfermera.

[Abstract] This clinical consensus statement reviews the use of inotropic support in patients with advanced heart failure. The current guidelines only support use of inotropes in the setting of acute decompensated heart failure with evidence of organ malperfusion or shock. However, inotropic support may be reasonable in other patients with advanced heart failure without acute severe decompensation. The clinical evidence supporting use of inotropes in these situations is reviewed. Particularly, patients with persistent congestion, systemic hypoperfusion, or advanced heart failure with need for palliation, and specific situations relevant to implantation of left ventricular assist devices or heart transplantation are discussed. Traditional and novel drugs with inotropic effects are discussed and use of guideline-directed therapy during inotropic support is reviewed. Finally, home inotropic therapy is described, and palliative care and end-of-life aspects are reviewed in relation to management of ongoing inotropic support (including guidance for maintenance and weaning of chronic inotropic therapy support).

[Abstract] Aims: Heart failure outcomes remain poor despite advances in therapy. The European Society of Cardiology Heart Failure III Registry (ESC HF III Registry) aims to characterize HF clinical features and outcomes and to assess implementation of guideline-recommended therapy in Europe and other ESC affiliated countries. Methods: Between 1 November 2018 and 31 December 2020, 10 162 patients with chronic or acute/worsening HF with reduced, mildly reduced, or preserved ejection fraction were enrolled from 220 centres in 41 European or ESC affiliated countries. The ESC HF III Registry collected data on baseline characteristics (hospital or clinic presentation), hospital course, diagnostic and therapeutic decisions in hospital and at the clinic visit; and on outcomes at 12-month follow-up. These data include demographics, medical history, physical examination, biomarkers and imaging, quality of life, treatments, and interventions - including drug doses and reasons for non-use, and cause-specific outcomes. Conclusion: The ESC HF III Registry will provide comprehensive and unique insight into contemporary HF characteristics, treatment implementation, and outcomes, and may impact implementation strategies, clinical discovery, trial design, and public policy.

[Abstract] Aims: Atrial fibrillation (AF) worsens the prognosis of patients with heart failure (HF). Successful treatments are still very scarce for those with permanent AF and preserved (HFpEF) or mildly reduced (HFmrEF) ejection fraction. In this study, the long-term benefits and safety profile of heart rate regularization through left-bundle branch pacing (LBBP) and atrioventricular node ablation (AVNA) will be explored in comparison with pharmacological rate-control strategy. Methods and results: The PACE-FIB trial is a multicentre, prospective, open-label, randomized (1:1) clinical study that will take place between March 2022 and February 2027. A total of 334 patients with HFpEF/HFmrEF and permanent AF will receive either LBBP followed by AVNA (intervention arm) or optimal pharmacological treatment for heart rate control according to European guideline recommendations (control arm). All patients will be followed up for a minimum of 36 months. The primary outcome measure will be the composite of all-cause mortality, HF hospitalization, and worsening HF at 36 months. Other secondary efficacy and safety outcome measures such as echocardiographic parameters, functional status, and treatment-related adverse events, among others, will be analysed too. Conclusion: LBBP is a promising stimulation mode that may foster the clinical benefit of heart rate regularization through AV node ablation compared with pharmacological rate control. This is the first randomized trial specifically addressing the long-term efficacy and safety of this pace-and-ablate strategy in patients with HFpEF/HFmrEF and permanent AF.

[Abstract] Background: We explored the changes in gene expression correlating with dysfunction and graft failure in endomyocardial biopsies. Methods: Genome-wide microarrays (19,462 genes) were used to define mRNA changes correlating with dysfunction (left ventricular ejection fraction [LVEF] ≤ 55) and risk of graft loss within 3 years postbiopsy. LVEF data was available for 1,013 biopsies and survival data for 779 patients (74 losses). Molecular classifiers were built for predicting dysfunction (LVEF ≤ 55) and postbiopsy 3-year survival. Results: Dysfunction is correlated with dedifferentiation-decreased expression of normal heart transcripts, for example, solute carriers, along with increased expression of inflammation genes. Many genes with reduced expression in dysfunction were matrix genes such as fibulin 1 and decorin. Gene ontology (GO) categories suggested matrix remodeling and inflammation, not rejection. Genes associated with the risk of failure postbiopsy overlapped dysfunction genes but also included genes affecting microcirculation, for example, arginase 2, which reduces NO production, and endothelin 1. GO terms also reflected increased glycolysis and response to hypoxia, but decreased VEGF and angiogenesis pathways. T cell-mediated rejection was associated with reduced survival and antibody-mediated rejection with relatively good survival, but the main determinants of survival were features of parenchymal injury. Both dysfunction and graft loss were correlated with increased biopsy expression of BNP (gene NPPB). Survival probability classifiers divided hearts into risk quintiles, with actuarial 3-year postbiopsy survival >95% for the highest versus 50% for the lowest. Conclusions: Dysfunction in transplanted hearts reflects dedifferentiation, decreased matrix genes, injury, and inflammation. The risk of short-term loss includes these changes but is also associated with microcirculation abnormalities, glycolysis, and response to hypoxia.

[Resumen] Introducción. El seguimiento clínico de pacientes trasplantados de corazón es complejo y requiere que la enfermera trasmita conocimientos según necesidades para fomentar el autocuidado y adherencia terapéutica. El objetivo fue evaluar la intervención educativa enfermera en pacientes trasplantados.Metodología. Se realizó un estudio observacional-descriptivo-transversal de los pacientes trasplantados de corazón en 2019 y 2020 (n=41) en la Unidad de Insuficiencia Cardiaca Avanzada del Hospital Universitario de A Coruña, a través de cuestionarios de conocimientos, evaluación y adherencia BAASIS©.Resultados. Participaron 41 pacientes con una edad media de 60,5 (±6,9), hombres el 80,5%. Según prioridad fueron 53,7% electivo. Respondieron correctamente a las 15 preguntas de conocimientos el 36,8%. Las preguntas con más errores fueron las relativas a los síntomas del rechazo.Todos los pacientes consideraron la información recibida útil y un 92,7% refirieron que les ayudó a mejorar la ansiedad y el miedo.El 87,2% tomaron tres fármacos inmunosupresores: tacrolimus 100%, de los cuales el 84,6% en una sola toma por la mañana, prednisona 97,4%, micofenolato de mofetilo 79,5% y everolimus 10,3%. Ningún paciente dejó de tomar los inmunosupresores por completo en el último año. Durante el último mes olvidaron o modificaron una vez la dosis pautada dos pacientes.El 69,2% de los pacientes puntuaron con el máximo su conducta sobre la toma de medicamentos inmunosupresores. Conclusiones. Los resultados obtenidos muestran que los pacientes mantienen, durante el primer año del trasplante de corazón, un nivel de conocimientos aceptable, buena adherencia a los inmunosupresores y consideran útil la intervención educativa-enfermera., [Abstract] Introduction. The clinical follow up of heart transplant patients is complex and requires the nurse to transmit knowledge according to needs to promote self-care and therapeutic adherence. The objective was to evaluate the nurse educational intervention in transplanted patients.Methodology. An observational-descriptive-transversal study was performed of patients who received heart transplants in 2019 and 2020 (n=41) at the Advanced Heart Failure Unit of the University Hospital of A Coruña using knowledge, assessment, and adherence questionnaires (BAASIS).Results. Forty-one patients participated with a mean age of 60.5 (±6.9), 80.5% were male. According to priority, 53.7% were elective. The 15 knowledge questions were answered correctly by 36.8%. The questions with more failures were those related to rejection symptoms.All patients considered the information received to be useful and 92.7% reported that it helped them improve their anxiety and fear.Three immunosuppressive drugs were taken by 87.2%: Tacrolimus 100%, of which 84.6% in a single morning dose, prednisone 97.4%, mycophenolate mofetil 79.5%, and everolimus 10.3%. No patient fully stopped taking immunosuppressants in the last year. During the last month, two patients forgot or changed the prescribed dose once.The maximum score was achieved by 69.2% of patients for their behavior regarding taking immunosuppressive drugs.Conclusions. The results obtained show that during the first year after heart transplantation, patients maintain an acceptable level of knowledge, good adherence to immunosuppressants, and consider the nurse educational intervention useful.

[Abstract] Aims: Aims were to evaluate (1) reclassification of patients from heart failure with mildly reduced (HFmrEF) to reduced (HFrEF) ejection fraction when an EF = 40% was considered as HFrEF, (2) role of EF digit bias, ie, EF reporting favouring 5% increments; (3) outcomes in relation to missing and biased EF reports, in a large multinational HF registry. Methods and results: Of 25,154 patients in the European Society of Cardiology (ESC) HF Long-Term registry, 17% had missing EF and of those with available EF, 24% had HFpEF (EF≥50%), 21% HFmrEF (40%-49%) and 55% HFrEF (<40%) according to the 2016 ESC guidelines´ classification. EF was "exactly" 40% in 7%, leading to reclassifying 34% of the HFmrEF population defined as EF = 40% to 49% to HFrEF when applying the 2021 ESC Guidelines classification (14% had HFmrEF as EF = 41% to 49% and 62% had HFrEF as EF≤40%). EF was reported as a value ending with 0 or 5 in ∼37% of the population. Such potential digit bias was associated with more missing values for other characteristics and higher risk of all-cause death and HF hospitalization. Patients with missing EF had higher risk of all-cause and CV mortality, and HF hospitalization compared to those with recorded EF. Conclusions: Many patients had reported EF = 40%. This led to substantial reclassification of EF from old HFmrEF (40%-49%) to new HFrEF (≤40%). There was considerable digit bias in EF reporting and missing EF reporting, which appeared to occur not at random and may reflect less rigorous overall care and worse outcomes.

[Resumen] Objetivos: En los últimos años han surgido publicaciones que sugieren que la insuficiencia cardiaca (IC) podría ser un factor de riesgo independiente de cáncer. No obstante, la evidencia publicada es por el momento débil. El objetivo principal de este estudio es analizar en pacientes con IC la incidencia de nueva neoplasia en el seguimiento, conocer los principales factores de riesgo asociados al desarrollo de nuevo cáncer y determinar su mortalidad y pronóstico, comparando estos resultados con los de la población general. Como objetivo secundario, analizamos asimismo el pronóstico de la IC en el paciente con antecedente de neoplasia previa. Métodos: Se trata de un estudio observacional y unicéntrico, basado en una cohorte histórica prospectiva de pacientes con IC remitidos a la Unidad de IC avanzada del Servicio de Cardiología del Complejo Hospitalario Universitario de A Coruña, en España, desde su creación en 2010 hasta 2019. El cáncer de piel no-melanoma fue excluido específicamente de la definición de nueva neoplasia, para poder comparar nuestros resultados con aquellos estimados para la población general española por el Observatorio Global de Cáncer. Resultados: Tras una mediana de seguimiento de 4,07 años de 1909 pacientes consecutivos con IC, se diagnosticaron 165 nuevos casos de neoplasia maligna. Las tasas de incidencia estandarizadas por edad por 100.000 personas-años observadas en el grupo de IC fueron de 861 casos [intervalo de confianza (ICo) 95% 618,4–2.159,4] en hombres y 728,5 casos (ICo 95% 451,1–4.308,7) en mujeres; mientras que las tasas de incidencia estandarizadas por edad por 100.000 personas-años para la población española fueron 479,4 casos en hombres (riesgo relativo = 1,80) y 295,5 casos en mujeres (riesgo relativo = 2,46). Tanto el desarrollo de neoplasia en el seguimiento como el antecedente de cáncer, se asociaron con una menor supervivencia. Las tasas de mortalidad relacionada con cáncer estandarizadas por edad por 100.000 per, [Resumo] Obxectivos: Nos últimos anos xurdiron publicacións que suxiren que a insuficiencia cardíaca (IC) podería ser un factor de risco independente de cancro. Non obstante, a evidencia publicada é polo momento feble. O obxectivo principal deste estudo é analizar en pacientes con IC a incidencia de nova neoplasia no seguimento, coñecer os principais factores de risco asociados ó desenvolvemento de cancro e determinar o seu prognóstico, comparando estes resultados cos da poboación xeral. Como obxectivo secundario, analizamos o prognóstico da IC no paciente con antecedente de neoplasia. Métodos: Tratase dun estudo observacional unicéntrico, baseado nunha cohorte histórica prospectiva de pacientes con IC remitidos á Unidade de IC Avanzada do Servizo de Cardioloxía do Complexo Hospitalario Universitario da Coruña, en España, desde a súa creación en 2010 ata 2019. O cancro de pel non-melanoma foi especificamente excluído da definición de malignidade, para poder comparar os nosos resultados cos estimados para a poboación xeral española polo Observatorio Global do Cancro. Resultados: Despois dunha mediana de seguimento de 4,07 anos de 1.909 pacientes consecutivos con IC, diagnosticáronse 165 novos casos de malignidade. As taxas de incidencia estandarizadas por idade por 100.000 persoas-anos foron de 861 casos [intervalo de confianza (ICo) 95% 618,4–2.159,4] en homes e 728,5 casos (ICo 95% 451,1–4.308,7) en mulleres no grupo de IC; mentres que as taxas de incidencia estandarizadas por idade por 100.000 persoas-anos para a poboación española foron 479,4 casos en homes (risco relativo = 1,80) e 295,5 casos en mulleres (risco relativo = 2,46). Tanto o antecedente de neoplasia como o diagnóstico dunha nova neoplasia no seguimento, foron asociadas cunha menor supervivencia. As taxas de mortalidade relacionada co cancro estandarizadas por idade por 100.000 persoas-anos foron 344,1 mortes (ICo 95% 202,1–1675) en homes e 217 mortes (ICo 95% 32,8–3949,3) en mulleres no grupo de IC, [Abstract] Objectives: During the last years publications have emerged suggesting heart failure (HF) might be an independent risk factor of cancer. Nevertheless, evidence published is for the time being weak. Therefore, the main endpoint of this study is to assess in patients with HF the incidence of the new diagnosis of malignancy, to analyse the major risk factors associated to the development of neoplasms, and to determinate its mortality and prognosis, comparing these outcomes with those related to the general population. As secondary endpoint, we analyse in addition the prognosis of HF in patients with a previous history of malignancy. Methods: We conducted an observational and single-center study based in a prospective cohort of patients with HF referred to the Advanced Heart Failure Unit of the Cardiology Service of A Coruña Universitary Hospital Complex, in Spain, since its creation in 2010 until 2019. Non-melanoma skin cancer was specifically excluded from the definition of newly diagnosed malignancies, with the purpose to compare our results with those estimated for the general Spanish population according to the Global Cancer Observatory. [Results] During follow-up of 1909 consecutive patients with HF over a median time of 4.07 years, 165 new cases of malignancy were diagnosed. Observed age-standardized incidence rates of cancer per 100,000 persons-years were 861 cases (95% Confidence Interval (CI) 618.4–2,159.4) in men and 728.5 cases (95% CI 451.1–4,308.7) in women in the HF group; while age-standardized incidence rates of cancer expected for the general Spanish population per 100,000 persons-years were 479.4 cases in men (risk ratio = 1.80) and 295.5 cases in women (risk ratio = 2.46). Both a history of pre-existing malignancy at baseline and the development of new malignancies during follow-up were associated with reduced survival. Observed age-standardized cancer-related mortality rates per 100,000 persons-years were 344.1 deaths (95% CI 202.1–1675)

[Abstract] Background The reported prevalence of donor-transmitted coronary artery disease (TCAD) in heart transplantation (HT) is variable, and its prognostic impact remains unclear. Objectives The goal of this study was to characterize TCAD in a contemporary multicentric cohort and to study its prognostic relevance. Methods This was a retrospective study of consecutive patients >18 years old who underwent HT in 11 Spanish centers from 2008 to 2018. Only patients with a coronary angiography (c-angio) within the first 3 months after HT were studied. Significant TCAD (s-TCAD) was defined as any stenosis ≥50% in epicardial coronary arteries, and nonsignificant TCAD (ns-TCAD) as stenosis <50%. Clinical outcomes were assessed by means of Cox regression and competing risks regression. Patients were followed-up for a median period of 6.3 years after c-angio. Results From a cohort of 1,918 patients, 937 underwent c-angio. TCAD was found in 172 patients (18.3%): s-TCAD in 65 (6.9%) and ns-TCAD in 107 (11.4%). Multivariable Cox regression analysis did not show a statistically significant association between s-TCAD and all-cause mortality (adjusted HR: 1.44; 95% CI: 0.89-2.35; P = 0.141); however, it was an independent predictor of cardiovascular mortality (adjusted HR: 2.25; 95% CI: 1.20-4.19; P = 0.011) and the combined event cardiovascular death or nonfatal MACE (adjusted HR: 2.42; 95% CI: 1.52-3.85; P < 0.001). No statistically significant impact of ns-TCAD on clinical outcomes was detected. The results were similar when reassessed by means of competing risks regression. Conclusions TCAD was not associated with reduced survival in patients alive and well enough to undergo post-HT angiography within the first 3 months; however, s-TCAD patients showed increased risk of cardiovascular death and MACE.

[Abstract] Purpose To describe the evolution of the serum levels of soluble HLA-G (s-HLA-G) during the first 12 months after heart transplantation (HT) and to correlate it with clinical outcomes. Methods Observational study based in a single-center cohort of 59 patients who underwent HT between December-2003 and March-2010. Soluble HLA-G levels were measured from serum samples extracted before HT, and 1, 3, 6 and 12 months after HT. The cumulative burden of s-HLA-G expression during the first post-transplant year was assessed by means of the area under the curve (AUC) of s-HLA-G levels over time and correlated with the acute rejection burden –as assessed by a rejection score–, the presence of coronary allograft vasculopathy (CAV) grade ≥ 1 and infections during the first post-transplant year; as well as with long-term patient and graft survival. Mean follow-up was 12.4 years. Results Soluble HLA-G levels decreased over the first post-transplant year (p = 0.020). The AUC of s-HLA-G levels during the first post-transplant year was higher among patients with infections vs. those without infections (p = 0.006). No association was found between the AUC of s-HLA-G levels and the burden of acute rejection or the development of CAV. Overall long-term survival, long-term survival free of late graft failure and cancer-free survival were not significantly different in patients with an AUC of s-HLA-G levels higher or lower than the median of the study population. Conclusions Soluble HLA-G levels decreased over the first year after HT. Higher HLA-G expression was associated with a higher frequency of infections, but not with the burden of acute rejection or the development of CAV, neither with long-term patient or graft survival.

[Abstract] Background: Women with heart failure with reduced ejection fraction (HFrEF) receive less guideline-recommended therapy and experience worse quality of life than men. Objectives: The authors sought to assess differences in baseline characteristics, outcomes, efficacy, and safety of omecamtiv mecarbil between men and women enrolled in the GALACTIC-HF (Registrational Study With Omecamtiv Mecarbil [AMG 423] to Treat Chronic Heart Failure With Reduced Ejection Fraction) study. Methods: In GALACTIC-HF, patients with symptomatic heart failure with EF of 35% or less, recent heart failure event, and elevated natriuretic peptides were randomized to omecamtiv mecarbil or placebo. The current analysis investigated differences in baseline characteristics, clinical outcomes, and efficacy and safety of omecamtiv mecarbil between men and women. Results: Of 8,232 patients analyzed, 21.2% were women. Women more likely self-identified as being Black, had worse symptoms (lower Kansas City Cardiomyopathy Questionnaire Total Symptom Score [KCCQ-TSS]), and were less likely to be treated with angiotensin receptor/neprilysin inhibitor and devices at baseline. Compared with men, women had lower rates of the primary endpoint (adjusted HR: 0.80, 95% CI: 0.73-0.88). Sex did not significantly modify omecamtiv mecarbil's treatment effect (P interaction = 0.68). Women also had 20% less risk of cardiovascular death, heart failure event, and all-cause death. Women participants had lower rates of serious adverse events. Conclusions: Women participants of the GALACTIC-HF trial had worse quality of life and were less likely to be treated with guideline-based therapies at baseline. Despite KCCQ-TSS being predictive of poor outcomes in this population, women had a 20% lower risk of an HF event or cardiovascular death compared with men. The beneficial effect of omecamtiv mecarbil did not significantly differ by sex. (Registrational Study With Omecamtiv Mecarbil [AMG 423] to Treat Chronic Heart

[Abstract] Background: Variants in RBM20 are reported in 2% to 6% of familial cases of dilated cardiomyopathy and may be associated with fatal ventricular arrhythmia and rapid heart failure progression. We sought to determine the risk of adverse events in RBM20 variant carriers and the impact of sex on outcomes. Methods: Consecutive probands and relatives carrying RBM20 variants were retrospectively recruited from 12 cardiomyopathy units. The primary end point was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF end points were also analyzed separately and men and women compared. Left ventricular ejection fraction (LVEF) contemporary to MVA was examined. RBM20 variant carriers with left ventricular systolic dysfunction (RBM20LVSD) were compared with variant-elusive patients with idiopathic left ventricular systolic dysfunction. Results: Longitudinal follow-up data were available for 143 RBM20 variant carriers (71 men; median age, 35.5 years); 7 of 143 had an MVA event at baseline. Thirty of 136 without baseline MVA (22.0%) reached the primary end point, and 16 of 136 (11.8%) had new MVA with no significant difference between men and women (log-rank P=0.07 and P=0.98, respectively). Twenty of 143 (14.0%) developed ESHF (17 men and 3 women; log-rank P<0.001). Four of 10 variant carriers with available LVEF contemporary to MVA had an LVEF >35%. At 5 years, 15 of 67 (22.4%) RBM20LVSD versus 7 of 197 (3.6%) patients with idiopathic left ventricular systolic dysfunction had reached the primary end point (log-rank P<0.001). RBM20 variant carriage conferred a 6.0-fold increase in risk of the primary end point. Conclusions: RBM20 variants are associated with a high risk of MVA and ESHF compared with idiopathic left ventricular systolic dysfunction. The risk of MVA in male and female RBM20 variant carriers is similar, but male sex is strongly associated with ESHF.

[Abstract] In this observational and multicenter study, that included all patients who underwent a heart transplantation (HT) in Spain from 1984 to 2018, we analyzed the incidence, management, and prognosis of colorectal cancer (CRC) after HT. Of 6,244 patients with a HT and a median follow-up of 8.8 years since the procedure, 116 CRC cases (11.5% of noncutaneous solid cancers other than lymphoma registered) were diagnosed, mainly adenocarcinomas, after a mean of 9.3 years post-HT. The incidence of CRC increased with age at HT from 56.6 per 100,000 person-years among under 45 year olds to 436.4 per 100,000 person-years among over 64 year olds. The incidence rates for age-at-diagnosis groups were significantly greater than those estimated for the general Spanish population. Curative surgery, performed for 62 of 74 operable tumors, increased the probability of patient survival since a diagnosis of CRC, from 31.6% to 75.7% at 2 years, and from 15.8% to 48.6% at 5 years, compared to patients with inoperable tumors. Our results suggest that the incidence of CRC among HT patients is greater than in the general population, increasing with age at HT.

[Resumen] Introducción: El HLA-G es producido por los aloinjertos y las células mononucleares infiltradas en los tejidos trasplantados. La expresión de HLA-G se induce en situaciones patológicas como las enfermedades autoinmunes, inflamatorias, infecciones víricas, cáncer y trasplantes. Los niveles elevados de HLA-G soluble (sHLA-G) se han relacionado significativamente con una mejor aceptación del injerto en los trasplantes de células madre hematopoyéticas, corazón, riñón e hígado/riñón. Objetivo: Describir la evolución de los niveles de sHLA-G durante los primeros 12 meses tras el trasplante cardiaco (TC) y correlación con eventos clínicos a corto y largo plazo. Métodos: Estudio observacional, unicéntrico, basado en una cohorte de 59 pacientes con TC realizado entre diciembre de 2003 y marzo de 2010. Se midieron los niveles de sHLA-G a partir de muestras de suero extraídas antes del TC, y a 1, 3, 6 y 12 meses después del TC. La concentración acumulada de expresión de sHLA-G durante el primer año postrasplante se evaluó mediante el área bajo la curva (ABC) de los niveles de sHLA-G a lo largo del tiempo y se correlacionó con la carga de rechazo agudo -evaluada mediante un score de rechazo-, la presencia de enfermedad vascular del injerto (EVI) CAV – ISHLT grado ≥1 y las infecciones durante el primer año tras el TC. Los resultados a largo plazo evaluados en este estudio fueron la supervivencia global, la supervivencia libre de hospitalización por disfunción tardía del injerto y la supervivencia libre de neoplasia. El seguimiento medio fue de 12,4 años. Resultados: Los niveles de sHLA-G disminuyeron durante el primer año postrasplante cardiaco (p=0,020). El ABC de los niveles de sHLA-G durante el primer año del TC fue mayor en los pacientes con infección frente a aquellos sin infección (p = 0,006). No se encontró ninguna asociación entre el ABC de los niveles de sHLA-G y la carga de rechazo agudo o el desarrollo de EVI en el primer año postrasplante. En cuanto a los e, [Resumo] Introducción: O HLA-G prodúcese por aloenxertos e células mononucleares que se infiltran nos tecidos transplantados. A expresión de HLA-G indúcese en situacións patolóxicas como enfermidades autoinmunes e inflamatorias, infeccións virais, cancro e transplantes. Os niveis elevados de HLA-G soluble (sHLA-G) asociáronse significativamente cunha mellor aceptación do enxerto nos transplantes de células nai hematopoiéticas, corazón, ril e fígado/ril. Obxectivo: Describir a evolución dos niveis de sHLA-G durante os primeiros 12 meses despois do transplante cardiaco (TC) e a súa correlación con eventos clínicos a curto e longo prazo. Métodos: Estudo observacional, unicéntrico, baseado nunha cohorte de 59 pacientes con TC realizado entre decembro de 2003 e marzo de 2010. Os niveis de sHLA-G medíronse a partir de mostras de soro tomadas antes do TC, e 1, 3, 6 e 12 meses despois do TC. A concentración acumulada de expresión de sHLA-G durante o primeiro ano despois do TC foi avaliada pola área baixo a curva (ABC) dos niveis de sHLA-G ao longo do tempo e correlacionouse coa carga do rexeitamento agudo -avaliado mediante unha puntuación de rexeitamento-, a presenza de enfermedade vascular do inxerto (EVI) -CAV – ISHLT grao ≥1 e infeccións durante o primeiro ano postransplante. Os resultados a longo prazo avaliados neste estudo foron a supervivencia global, a supervivencia libre de hospitalización por disfunción tardía do enxerto e a supervivencia libre de neoplasia. O seguimento medio foi de 12,4 anos Resultados: Os niveis de sHLA-G diminuíron durante o primeiro ano postransplante (p=0,020). A ABC dos niveis de sHLA-G durante o primeiro ano despois do TC foi maior nos pacientes con infección en comparación cos sen infección (p = 0,006). Non se atopou ningunha asociación entre a ABC dos niveis de sHLA-G e a carga de rexeitamento agudo ou o desenvolvemento de EVI no primeiro ano tralo TC. Respecto aos eventos a longo prazo, a supervivencia global, a supervivencia libre de, [Abstract] Introduction: HLA-G has been described to be produced by allografts and infiltrating mononuclear cells within the transplanted tissues. The expression of HLA-G is induced in pathological situations such autoimmune disorders, inflammation, viral infections, cancer and transplantation. High levels of soluble HLA-G (sHLA-G) have been significantly related with better graft acceptance in hematopoietic stem cell-, heart-, kidney- and liver/kidney transplants Purpose: To describe the evolution of s-HLA-G during the first 12 months after heart transplantation (HT) and to correlate it with clinical outcomes. Methods: Observational study based in a single-center cohort of 59 patients who underwent HT between December-2003 and March-2010. sHLA-G levels were measured from serum samples extracted before HT, and 1, 3, 6 and 12 months after HT. The cumulative burden of sHLA-G expression during the first post-transplant year was assessed by means of the area under the curve (AUC) of sHLA-G levels over time and correlated with the acute rejection burden -as assessed by a rejection score-, the presence of cardiac allograft vasculopathy (CAV) grade ≥ 1 and infections during the first post-transplant year. Long-term outcomes evaluated in this study were overall survival, survival free of late graft failure and survival free of cancer. Mean follow-up was 12.4 years. Results: Levels of sHLA-G decreased over the first post-transplant year (p=0.020). The AUC of sHLA-G levels during the first post-transplant year was higher among patients with infections vs. those without infections (p = 0.006). No association was found between the AUC of sHLA-G levels and the burden of acute rejection or the development of CAV. Overall long-term survival, long-term survival free of late graft failure and cancer-free survival were not significantly different in patients with an AUC of sHLA-G levels higher or lower than the median of the study population. Conclusions: Levels of sHLA-G decreased o

[Abstract] Aims: To assess the prevalence, clinical characteristics, and outcomes of patients with heart failure (HF) with or without moderate to severe aortic valve disease (AVD) (aortic stenosis [AS], aortic regurgitation [AR], mixed AVD [MAVD]). Methods and results: Data from the prospective ESC HFA EORP HF Long-Term Registry including both chronic and acute HF were analysed. Of 15 216 patients with HF (62.5% with reduced ejection fraction, HFrEF; 14.0% with mildly reduced ejection fraction, HFmrEF; 23.5% with preserved ejection fraction, HFpEF), 706 patients (4.6%) had AR, 648 (4.3%) AS and 234 (1.5%) MAVD. The prevalence of AS, AR and MAVD was 6%, 8%, and 3% in HFpEF, 6%, 3%, and 2% in HFmrEF and 4%, 3%, and 1% in HFrEF. The strongest associations were observed for age and HFpEF with AS, and for left ventricular end-diastolic diameter with AR. AS (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.23-1.67), and MAVD (adjusted HR 1.37, 95% CI 1.07-1.74) but not AR (adjusted HR 1.13, 95% CI 0.96-1.33) were independently associated with the 12-month composite outcome of cardiovascular death and HF hospitalization. The associations between AS and the composite outcome were observed regardless of ejection fraction category. Conclusions: In the ESC HFA EORP HF Long-Term Registry, one in 10 patients with HF had AVD, with AS and MAVD being especially common in HFpEF and AR being similarly distributed across all ejection fraction categories. AS and MAVD, but not AR, were independently associated with increased risk of in-hospital mortality and 12-month composite outcome, regardless of ejection fraction category.

[Abstract] Essential oils sourced from herbs commonly used in the Mediterranean diet have demonstrated advantageous attributes as nutraceuticals and prebiotics within a model of severe cardiometabolic disorder. The primary objective of this study was to assess the influences exerted by essential oils derived from thyme (Thymus vulgaris) and oregano (Origanum vulgare) via a comprehensive multi-omics approach within a gnotobiotic murine model featuring colonic microbiota acquired from patients diagnosed with coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM). Our findings demonstrated prebiotic and potential antioxidant effects elicited by these essential oils. We observed a substantial increase in the relative abundance of the Lactobacillus genus in the gut microbiota, accompanied by higher levels of short-chain fatty acids and a reduction in trimethylamine N-oxide levels and protein oxidation in the plasma. Moreover, functional enrichment analysis of the cardiac tissue proteome unveiled an over-representation of pathways related to mitochondrial function, oxidative stress, and cardiac contraction. These findings provide compelling evidence of the prebiotic and antioxidant actions of thyme- and oregano-derived essential oils, which extend to cardiac function. These results encourage further investigation into the promising utility of essential oils derived from herbs commonly used in the Mediterranean diet as potential nutraceutical interventions for mitigating chronic diseases linked to CAD and T2DM.

[Abstract] Aims: To comprehensively assess hyponatraemia in acute heart failure (AHF) regarding prevalence, associations, hospital course, and post-discharge outcomes. Methods and results: Of 8298 patients in the European Society of Cardiology Heart Failure Long-Term Registry hospitalized for AHF with any ejection fraction, 20% presented with hyponatraemia (serum sodium <135 mmol/L). Independent predictors included lower systolic blood pressure, estimated glomerular filtration rate (eGFR) and haemoglobin, along with diabetes, hepatic disease, use of thiazide diuretics, mineralocorticoid receptor antagonists, digoxin, higher doses of loop diuretics, and non-use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta-blockers. In-hospital death occurred in 3.3%. The prevalence of hyponatraemia and in-hospital mortality with different combinations were: 9% hyponatraemia both at admission and discharge (hyponatraemia Yes/Yes, in-hospital mortality 6.9%), 11% Yes/No (in-hospital mortality 4.9%), 8% No/Yes (in-hospital mortality 4.7%), and 72% No/No (in-hospital mortality 2.4%). Correction of hyponatraemia was associated with improvement in eGFR. In-hospital development of hyponatraemia was associated with greater diuretic use and worsening eGFR but also more effective decongestion. Among hospital survivors, 12-month mortality was 19% and adjusted hazard ratios (95% confidence intervals) were for hyponatraemia Yes/Yes 1.60 (1.35-1.89), Yes/No 1.35 (1.14-1.59), and No/Yes 1.18 (0.96-1.45). For death or heart failure hospitalization they were 1.38 (1.21-1.58), 1.17 (1.02-1.33), and 1.09 (0.93-1.27), respectively. Conclusion: Among patients with AHF, 20% had hyponatraemia at admission, which was associated with more advanced heart failure and normalized in half of patients during hospitalization. Admission hyponatraemia (possibly dilutional), especially if it did not resolve, was associated with worse in-hospital and post-discharge outcomes. Hypona

[Resumen] INTRODUCCIÓN: Espironolactona y eplerenona presentan, según las guías de práctica clínica, un mismo grado de recomendación para el tratamiento de la insuficiencia cardiaca con fracción de eyección reducida (IC-FEr) sintomática, ya que ambos fármacos han demostrado de forma consistente una reducción de la morbimortalidad en estos pacientes. Sin embargo, dada la ausencia de estudios comparativos directos, se desconoce si pueden existir diferencias entre ellos en cuanto a su beneficio pronóstico. OBJETIVOS: El objetivo de este estudio fue evaluar la efectividad de espironolactona y eplerenona en pacientes con IC-FEr en un escenario clínico de vida real. MÉTODOS: Utilizando la regresión de Fine-Gray para riesgos competitivos, comparamos los eventos clínicos de 293 pacientes con insuficiencia cardiaca (IC) crónica y fracción de eyección <40% tratados con eplerenona con 293 individuos tratados con espironolactona emparejados por puntuación de propensión. Los pacientes del estudio fueron seleccionados de una cohorte prospectiva de 1404 pacientes ambulatorios con IC-FEr valorados desde 2010 hasta 2019 en una única unidad especializada de IC, de los cuales 992 recibieron tratamiento con un antagonista del receptor mineralocorticoide basalmente. La mediana de seguimiento fue de 3,95 años. RESULTADOS: No se observaron diferencias significativas entre pacientes tratados con eplerenona versus espironolactona en cuanto al objetivo primario combinado de muerte cardiovascular u hospitalización por IC [hazard ratio (HR) 0,95; intervalo de confianza al 95% (IC 95%) 0,73-1,23; p=0,677]. Sin embargo, el uso de eplerenona se asoció a una menor mortalidad cardiovascular (HR 0,55; IC 95% 0,35-0,85; p=0,008) y a una menor mortalidad por todas las causas (HR 0,67; IC 95% 0,47-0,95; p=0,027). La incidencia de suspensión del fármaco debido a efectos adversos (HR 0,58; IC 95% 0,40-0,85; p=0,005) y debido a cualquier causa (HR 0,70; IC 95% 0,51-0,97; p=0,033) fue menor en los paciente, [Resumo] INTRODUCIÓN: Espironolactona e eplerenona presentan, segundo as guías de práctica clínica, un mesmo grao de recomendación para o tratamento da insuficiencia cardíaca con fracción de exección reducida (IC-FEr) sintomática, xa que os dous fármacos teñen demostrado de forma consistente unha redución da morbimortalidade destes pacientes. Non obstante, dada a ausencia de estudos comparativos directos, descoñécese se poden existir diferenzas entre eles en canto ó seu beneficio prognóstico. OBXECTIVOS: O obxectivo deste estudo foi avaliar a efectividade de espironolactona e eplerenona en pacientes con IC-FEr nun escenario clínico de vida real. MÉTODOS: Utilizando a regresión de Fine-Gray para riscos competitivos, comparamos os eventos clínicos de 293 pacientes con insuficiencia cardíaca (IC) crónica e fracción de exección <40% tratados con eplerenona con 293 individuos tratados con espironolactona emparellados por puntuación de propensión. Os pacientes do estudo foron seleccionados dunha cohorte prospectiva de 1404 pacientes ambulatorios con IC-FEr valorados dende 2010 ata 2019 nunha única unidade especializada de IC, dos cales 992 recibiron tratamento cun antagonista do receptor mineralocorticoide basalmente. A mediana de seguimento foi de 3,95 anos. RESULTADOS: Non se observaron diferenzas significativas entre pacientes tratados con eplerenona versus espironolactona no tocante ó obxectivo primario combinado de morte cardiovascular ou hospitalización por IC [hazard ratio (HR) 0,95; intervalo de confianza ó 95% (IC 95%) 0,73-1,23; p=0,677]. Non obstante, o uso de eplerenona asociouse a unha menor mortalidade cardiovascular (HR 0,55; IC 95% 0,35-0,85; p=0,008) e a unha menor mortalidade por todas as causas (HR 0,67; IC 95% 0,47-0,95; p=0,027). A incidencia de suspensión do fármaco debido a efectos adversos (HR 0,58; IC 95% 0,40-0,85; p=0,005) e debido a calquera causa (HR 0,70; IC 95% 0,51-0,97; p=0,033) foi menor nos pacientes a tratamento con eplerenona. CONCLUSI, [Abstract] INTRODUCTION: Spironolactone and eplerenone are both recommended for the treatment of heart failure and reduced ejection fraction (HFrEF) according to practice guidelines, as both drugs demonstrated consistent reductions of mortality and morbidity in these patients. However, given the absence of direct comparative studies, it is not known whether any differences regarding their prognostic benefit can exist between them. OBJECTIVES: We aimed to evaluate the effectiveness of spironolactone and eplerenone in patients with HFrEF in a real-world clinical setting. METHODS: Using Fine-Gray´s competing risk regression, we compared the clinical outcomes of 293 patients with chronic heart failure (HF) and left ventricular ejection fraction <40% treated with eplerenone and 293 propensity-score matched individuals treated with spironolactone. Study subjects were selected from a prospective cohort of 1404 ambulatory patients with HFrEF seen since 2010 to 2019 in a single specialized HF clinic, among which 992 received a mineralocorticoid receptor antagonist at baseline. Median follow-up was 3.95 years. RESULTS: No statistically significant differences between patients treated with eplerenone versus spironolactone were observed with regard to the risk of the primary composite end-point cardiovascular death or HF hospitalization [hazard ratio (HR) 0.95; 95% confidence interval (95% CI) 0.73-1.23; p=0.677]. However, eplerenone use was associated to lower cardiovascular mortality (HR 0.55; 95% CI 0.35-0.85; p=0.008) and lower all-cause mortality (HR 0.67; 95% CI 0.47-0.95; p=0.027). The incidence of drug suspension due to side effects (HR 0.58; 95% CI 0.40-0.85; p=0.005) and drug suspension due to any reason (HR 0.70; 95% CI 0.51-0.97; p=0.033) were lower among patients treated with eplerenone. CONCLUSIONS: In this observational, real-world, propensity-score matched study of patients with HFrEF, no statistically significant differences between patients treated with eplere