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Background: Oral activated factor XI (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without substantially increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI). Methods: We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6 to 12 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on FXIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo. Results: The median age was 68 years, 23% of participants were women, 51% had ST-segment–elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity, with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian versus placebo: hazard ratio, 0.98 [90% CI, 0.71–1.35]). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian 20 and 50 mg versus placebo: hazard ratio, 1.05 [90% CI, 0.69–1.61]). Conclusions: In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients who experienced acute MI. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04304534; URL: https://www.clinicaltrialsregister.eu/ctr-search/search ; Unique identifier: 2019-003244-79.

Introduction and objectives Transcatheter aortic valve implant has become a widely accepted treatment for inoperable patients with aortic stenosis and patients at high surgical risk. Its indications have recently been expanded to include patients at intermediate and low surgical risk. Our aim was to evaluate the efficiency of SAPIEN 3 vs conservative medical treatment (CMT) or surgical aortic valve replacement (SAVR) in symptomatic inoperable patients at high or intermediate risk. Methods We conducted a cost-effectiveness analysis of SAPIEN 3 vs SAVR/CMT, using a Markov model (monthly cycles) with 8 states defined by the New York Heart Association and a time horizon of 15 years, including major complications and management after hospital discharge, from the perspective of the National Health System. Effectiveness parameters were based on the PARTNER trials. Costs related to the procedure, hospitalization, complications, and follow-up were included (euros in 2019). An annual discount rate of 3% was applied to both costs and benefits. Deterministic and probabilistic sensitivity analyses (Monte Carlo) were performed. Results Compared with SAVR (high and intermediate risk) and CMT (inoperable), SAPIEN 3 showed better clinical results in the 3 populations and lower hospital stay. Incremental cost-utility ratios (€/quality-adjusted life years gained) were 5471 (high risk), 8119 (intermediate risk) and 9948 (inoperable), respectively. In the probabilistic analysis, SAPIEN 3 was cost-effective in more than 75% of the simulations in the 3 profiles. Conclusions In our health system, SAPIEN 3 facilitates efficient management of severe aortic stenosis in inoperable and high- and intermediate-risk patients.

Resumen Introduccion y objetivos La ventilacion no invasiva (VNI) es capaz de reducir la necesidad de intubacion endotraqueal y la mortalidad de los pacientes con insuficiencia cardiaca aguda (ICA). Sin embargo, de muchos de los ensayos clinicos se ha excluido a los pacientes con ICA secundaria a sindrome coronario agudo o infarto agudo de miocardio (SCA-IAM). El objetivo de este estudio es comparar la efectividad de la VNI entre pacientes con ICA desencadenada por SCA-IAM y por otras causas. Metodos Estudio prospectivo de cohortes, durante un periodo de 20 anos, de todos los pacientes con ICA tratados con VNI ingresados en una unidad de cuidados intensivos. Se agrupo a los pacientes por la presencia o ausencia de SCA-IAM como causante del evento de ICA. Se definio el fracaso de la VNI por la necesidad de intubacion endotraqueal o muerte. Resultados Se analizo a 1.009 pacientes, 403 (40%) con SCA-IAM y 606 (60%) con otras etiologias. La VNI fracaso en 61 casos (15,1%) del grupo de SCA-IAM y 64 (10,6%) del grupo sin SCA-IAM (p = 0,031), sin diferencias en la mortalidad hospitalaria (el 16,6 y el 14,9%; p = 0,478). Conclusiones El SCA-IAM como causa desencadenante de la ICA no influye en el pronostico de los pacientes con insuficiencia respiratoria aguda que precisan asistencia respiratoria no invasiva.

Introduction and objectives Noninvasive ventilation (NIV) has been shown to reduce the rate of endotracheal intubation and mortality in patients with acute heart failure (AHF). However, patients with AHF secondary to acute coronary syndrome/acute myocardial infarction (ACS-AMI) have been excluded from many clinical trials. The purpose of this study was to compare the effectiveness of NIV between patients with AHF triggered by ACS-AMI and by other etiologies. Methods Prospective cohort study of all patients with AHF treated with NIV admitted to the intensive care unit for a period of 20 years. Patients were divided according to whether they had ACS-AMI as the cause of the AHF episode. NIV failure was defined as the need for endotracheal intubation or death. Results A total of 1009 patients were analyzed, 403 (40%) showed ACS-AMI and 606 (60%) other etiologies. NIV failure occurred in 61 (15.1%) in the ACS-AMI group and in 64 (10.6%) in the other group (P = .031), without differences in in-hospital mortality (16.6% and 14.9%, respectively; P = .478). Conclusions The presence of ACS-AMI as the triggering cause of AHF did not influence patients with acute respiratory failure requiring noninvasive respiratory support .

Resumen Introduccion y objetivos Se presentan las caracteristicas clinicas y los resultados de los trasplantes cardiacos realizados en Espana con la actualizacion correspondiente a 2019. Metodos Se describen las caracteristicas clinicas y los resultados de los trasplantes cardiacos realizados en 2019, asi como las tendencias de estos en el periodo 2010-2018. Resultados En 2019 se realizaron 300 trasplantes (8.794 desde 1984; 2.745 entre 2010 y 2019). Respecto a anos previos, los cambios mas llamativos son el descenso hasta el 38% de los trasplantes realizados en codigo urgente, y la consolidacion en el cambio de asistencia circulatoria pretrasplante, con la practica desaparicion del balon de contrapulsacion (0,7%), la estabilizacion del uso del oxigenador extracorporeo de membrana (9,6%) y el aumento de los dispositivos de asistencia ventricular (29%). La supervivencia en el trienio 2016-2018 es similar a la del trienio 2013-2015 (p = 0,34), y ambas mejores que la del trienio 2010-2012 (p = 0,002 y p = 0,01 respectivamente). Conclusiones Se mantienen estables tanto la actividad del trasplante cardiaco en Espana como los resultados en supervivencia en los ultimos 2 trienios. Hay una tendencia a realizar menos trasplantes urgentes, la mayoria con dispositivos de asistencia ventricular.

Domingo A Pascual-Figal,1– 3 Aychel E Roura-Piloto,4 Encarnación Moral-Escudero,4 Enrique Bernal,5 Helena Albendín-Iglesias,4 M Teresa Pérez-Martínez,1 Jose Antonio Noguera-Velasco,6 Iria Cebreiros-López,6 Álvaro Hernández-Vicente,1 David Vázquez-Andrés,1 Carmen Sánchez-Pérez,2 Amjad Khan,7 Fátima Sánchez-Cabo,3 Elisa García-Vázquez4 On behalf of the COL-COVID Investigators1Cardiology Department, Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Universidad de Murcia, Murcia, Spain; 2Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, (CIBERCV), Madrid, Spain; 3Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; 4Infectious Diseases and Internal Medicine Department, Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Universidad de Murcia, Murcia, Spain; 5Infectious Diseases and Internal Medicine Department, Hospital Universitario Reina Sofia, IMIB-Arrixaca, Universidad de Murcia, Murcia, Spain; 6Clinical Biochemistry Department, Hospital Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Universidad de Murcia, Murcia, Spain; 7Department of Chemistry, University of Oxford, Oxford, UKCorrespondence: Domingo A Pascual-FigalLAIB, Despacho 2.52, Av. Buenavista s/n, Murcia, 30120, SpainTel +34-868888163Email dpascual@um.esBackground: Colchicine has been proposed as a potential therapy in coronavirus disease 2019 (COVID-19) due to their anti-inflammatory actions.Methods: The COL-COVID study was a prospective, randomized, controlled and open-label clinical trial that compared colchicine added to standard treatment vs standard treatment in hospitalized COVID-19 patients that do not need mechanical ventilatory support. Colchicine was initiated within the first 48 hours of admission at a 1.5 mg loading dose, followed by 0.5 mg b.i.d. for one week and 0.5 mg per day for 28 days. The study endpoints were clinical status (7-points WHO ordinal scale) and inflammatory biomarkers (IL-6 and CRP).Results: A total of 103 patients (51± 12 years, 52% male) were randomly allocated to colchicine arm (n=52) and control arm (n=51). At day 28, all patients in the colchicine group were alive and discharged, whereas in the control group, two patients died in-hospital and one patient remained hospitalized. Clinical improvement in terms of changes on WHO scale at day 14 and 28 and time to 1-point clinical improvement did not differ between the two groups. Clinical deterioration (increase of at least 1-point in WHO scale) was observed in a higher proportion of cases in colchicine group (13.8%) vs control group (5.8%) (p=0.303); after adjustment by baseline risk factors and concomitant therapies, colchicine therapy was associated with a lower risk of clinical deterioration (p=0.030). Inflammatory biomarkers CRP and IL-6 concentrations course did not differ between the two arms.Conclusion: In hospitalized COVID-19 patients, colchicine treatment neither improved the clinical status, nor the inflammatory response, over the standard treatment. Nevertheless, a preventive effect for further clinical deterioration might be possible.Trial Registration: NCT04350320.Keywords: colchicine, COVID-19, inflammation

Background The diagnosis of acute myocarditis typically requires either endomyocardial biopsy (which is invasive) or cardiovascular magnetic resonance imaging (which is not universally available). Additional approaches to diagnosis are desirable. We sought to identify a novel microRNA for the diagnosis of acute myocarditis. Methods To identify a microRNA specific for myocarditis, we performed microRNA microarray analyses and quantitative polymerase-chain-reaction (qPCR) assays in sorted CD4+ T cells and type 17 helper T (Th17) cells after inducing experimental autoimmune myocarditis or myocardial infarction in mice. We also performed qPCR in samples from coxsackievirus-induced myocarditis in mice. We then identified the human homologue for this microRNA and compared its expression in plasma obtained from patients with acute myocarditis with the expression in various controls. Results We confirmed that Th17 cells, which are characterized by the production of interleukin-17, are a characteristic feature of myocardial injury in the acute phase of myocarditis. The microRNA mmu-miR-721 was synthesized by Th17 cells and was present in the plasma of mice with acute autoimmune or viral myocarditis but not in those with acute myocardial infarction. The human homologue, designated hsa-miR-Chr8:96, was identified in four independent cohorts of patients with myocarditis. The area under the receiver-operating-characteristic curve for this novel microRNA for distinguishing patients with acute myocarditis from those with myocardial infarction was 0.927 (95% confidence interval, 0.879 to 0.975). The microRNA retained its diagnostic value in models after adjustment for age, sex, ejection fraction, and serum troponin level. Conclusions After identifying a novel microRNA in mice and humans with myocarditis, we found that the human homologue (hsa-miR-Chr8:96) could be used to distinguish patients with myocarditis from those with myocardial infarction. (Funded by the Spanish Ministry of Science and Innovation and others.).

Clonal hematopoiesis driven by somatic mutations in hematopoietic cells, frequently called clonal hematopoiesis of indeterminate potential (CHIP), has been associated with adverse cardiovascular outcomes in population-based studies and in patients with ischemic heart failure (HF) and reduced left ventricular ejection fraction (LVEF). Yet, the impact of CHIP on HF progression, including nonischemic etiology, is unknown.The purpose of this study was to assess the clinical impact of clonal hematopoiesis on HF progression irrespective of its etiology.The study cohort comprised 62 patients with HF and LVEF 45% (age 74 ± 7 years, 74% men, 52% nonischemic, and LVEF 30 ± 8%). Deep sequencing was used to detect CHIP mutations with a variant allelic fraction2% in 54 genes. Patients were followed for at least 3.5 years for various adverse events including death, HF-related death, and HF hospitalization.CHIP mutations were detected in 24 (38.7%) patients, without significant differences in all-cause mortality (p = 0.151). After adjusting for risk factors, patients with mutations in either DNA methyltransferase 3 alpha (DNMT3A) or Tet methylcytosine dioxygenase 2 (TET2) exhibited accelerated HF progression in terms of death (hazard ratio [HR]: 2.79; 95% confidence interval [CI]: 1.31 to 5.92; p = 0.008), death or HF hospitalization (HR: 3.84; 95% CI: 1.84 to 8.04; p 0.001) and HF-related death or HF hospitalization (HR: 4.41; 95% CI: 2.15 to 9.03; p 0.001). In single gene-specific analyses, somatic mutations in DNMT3A or TET2 retained prognostic significance with regard to HF-related death or HF hospitalization (HR: 4.50; 95% CI: 2.07 to 9.74; p 0.001, for DNMT3A mutations; HR: 3.18; 95% CI: 1.52 to 6.66; p = 0.002, for TET2 mutations). This association remained significant irrespective of ischemic/nonischemic etiology.Somatic mutations that drive clonal hematopoiesis are common among HF patients with reduced LVEF and are associated with accelerated HF progression regardless of etiology.

Background: Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure. Methods: AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin

Introducción y objetivos Se presentan las características clínicas y los resultados de los trasplantes cardiacos realizados en España con la actualización correspondiente a 2019. Métodos Se describen las características clínicas y los resultados de los trasplantes cardiacos realizados en 2019, así como las tendencias de estos en el periodo 2010-2018. Resultados En 2019 se realizaron 300 trasplantes (8.794 desde 1984; 2.745 entre 2010 y 2019). Respecto a años previos, los cambios más llamativos son el descenso hasta el 38% de los trasplantes realizados en código urgente, y la consolidación en el cambio de asistencia circulatoria pretrasplante, con la práctica desaparición del balón de contrapulsación (0, 7%), la estabilización del uso del oxigenador extracorpóreo de membrana (9, 6%) y el aumento de los dispositivos de asistencia ventricular (29%). La supervivencia en el trienio 2016-2018 es similar a la del trienio 2013-2015 (p = 0, 34), y ambas mejores que la del trienio 2010-2012 (p = 0, 002 y p = 0, 01 respectivamente). Conclusiones Se mantienen estables tanto la actividad del trasplante cardiaco en España como los resultados en supervivencia en los últimos 2 trienios. Hay una tendencia a realizar menos trasplantes urgentes, la mayoría con dispositivos de asistencia ventricular. Introduction and objectives: The present report describes the clinical characteristics and outcomes of heart transplants in Spain and updates the data to 2019. Methods: We describe the clinical characteristics and outcomes of heart transplants performed in Spain in 2019, as well as trends in this procedure from 2010 to 2018. Results: In 2019, 300 transplants were performed (8794 since 1984; 2745 between 2010 and 2019). Compared with previous years, the most notable findings were the decreasing rate of urgent transplants (38%), and the consolidation of the type of circulatory support prior to transplant, with an almost complete disappearance of counterpulsation balloon (0.7%), stabilization in the use of extracorporeal membrane oxygenation (9.6%), and an increase in the use of ventricular assist devices (29.0%). Survival from 2016 to 2018 was similar to that from 2013 to 2015 (P = .34). Survival in both these periods was better than that from 2010 to 2012 (P = .002 and P = .01, respectively). Conclusions: Heart transplant activity has remained stable during the last few years, as have outcomes (in terms of survival). There has been a trend to a lower rate of urgent transplants and to a higher use of ventricular assist devices prior to transplant.

Resumen Introduccion y objetivos La insuficiencia cardiaca (IC) es un problema creciente de salud y una carga importante para la sociedad. Pese a ello, con frecuencia se minusvalora globalmente la gravedad del pronostico. Este estudio estima el pronostico al ano en pacientes con IC aguda y cronica en Espana y resto de Europa. Metodos Un total de 2.829 pacientes con IC (589 IC aguda y 2.240 IC cronica) seleccionados en 27 centros hospitalarios en Espana, atendidos por cardiologos y que participan en el registro ESC-EORP-HFA Heart Failure Long-Term, con 211 centros y 12.440 pacientes en total, se siguieron un ano para monitorizar la mortalidad y el ingreso hospitalario. Resultados La mortalidad al ano en IC aguda fue del 29,3% en Espana (IC95%, 25,6-33,2) y 27,7% en el resto de Europa (p = 0,4303). En IC cronica, las cifras correspondientes fueron 6,4% (IC95%, 5,4-7,5) y 9,5% (p Conclusiones Se confirma la gravedad de la IC, en particular cuando ya necesita ingreso, incluso en centros con buen seguimiento de guias clinicas. En pacientes ingresados por IC en Espana casi un tercio fallecera en el primer ano tras ese ingreso indice (incluyendo el 5,9% que fallece durante el mismo) y casi la mitad fallecera o necesitara reingresar por IC. La comparacion favorable con Europa en hospitalizaciones y mortalidad en IC cronica se debe interpretar con cautela por insuficiente ajuste por potenciales variables de confusion.

Introduction and objectives In patients with heart failure and reduced ejection fraction (HFrEF), several therapies have been proven to reduce mortality in clinical trials. However, there are few data on the effect of the use of evidence-based therapies on causes of death in clinical practice. Methods This study included 2351 outpatients with HFrEF ( Results Patients in REDINSCOR I more frequently received beta-blockers (85% vs 71%; P Conclusions In ambulatory patients with HFrEF, implementation of evidence-based therapies was associated with a lower risk of death, mainly due to a significant reduction in sudden cardiac death.

Introduction and objectives In patients with heart failure and reduced ejection fraction (HFrEF), several therapies have been proven to reduce mortality in clinical trials. However, there are few data on the effect of the use of evidence-based therapies on causes of death in clinical practice. Methods This study included 2351 outpatients with HFrEF (< 40%) from 2 multicenter prospective registries: MUSIC (n=641, period: 2003-2004) and REDINSCOR I (n=1710, period: 2007-2011). Variables were recorded at inclusion and all patients were followed-up for 4 years. Causes of death were validated by an independent committee. Results Patients in REDINSCOR I more frequently received beta-blockers (85% vs 71%; P

Resumen Introduccion y objetivos La insuficiencia cardiaca (IC) avanzada conlleva altas tasas de hospitalizacion y mortalidad. El estudio LION-HEART fue un ensayo clinico aleatorizado y controlado con placebo que evaluo la eficacia y la seguridad de la administracion intravenosa de dosis intermitentes de levosimendan en pacientes ambulatorios con IC avanzada. El objetivo del presente estudio es realizar un analisis de costes para determinar si la menor tasa de hospitalizaciones por IC observada en pacientes tratados con levosimendan en el estudio LION-HEART puede generar ahorros para el Sistema Nacional de Salud, en comparacion con la opcion de no tratar a los pacientes con IC avanzada. Metodos Se realizo un modelo economico que incluyo las tasas de hospitalizacion por IC del estudio LION-HEART y los costes de hospitalizacion por IC y de adquisicion y administracion intravenosa de levosimendan. El horizonte temporal del analisis fue de 12 meses. Se realizaron 2 analisis, uno deterministico y otro probabilistico (simulacion de Monte Carlo de segundo orden). Resultados Segun el analisis deterministico, el ahorro total por cada paciente tratado con levosimendan ascenderia a –698,48 euros. En el analisis probabilistico, el ahorro por paciente tratado con levosimendan seria de –849,94 (IC95%, 133,12 a –2.255,31) euros. La probabilidad de que se produzcan ahorros con levosimendan en comparacion con la opcion de no tratar seria del 94,8%. Conclusiones El tratamiento ambulatorio intermitente con levosimendan puede generar ahorros para el Sistema Nacional de Salud, en comparacion con la opcion de no tratar a los pacientes con IC avanzada.

Resumen Introduccion y objetivos La hiperpotasemia es una preocupacion creciente en el tratamiento de los pacientes con insuficiencia cardiaca y fraccion de eyeccion reducida, pues limita el uso de farmacos eficaces. Este trabajo ofrece estimaciones de la magnitud de este problema en la practica clinica habitual en Espana, los cambios en las concentraciones de potasio en el seguimiento y los factores asociados. Metodos Pacientes con insuficiencia cardiaca aguda (n = 881) y cronica (n = 3.587) seleccionados en 28 hospitales espanoles del registro europeo de insuficiencia cardiaca de la European Society of Cardiology y seguidos 1 ano para diferentes desenlaces, incluidos cambios en las cifras de potasio y su impacto en el tratamiento. Resultados La hiperpotasemia (K+ > 5,4 mEq/l) esta presente en el 4,3% (IC95%, 3,7-5,0%) y el 8,2% (6,5-10,2%) de los pacientes con insuficiencia cardiaca cronica y aguda; causa el 28,9% de todos los casos en que se contraindica el uso de antagonistas del receptor de mineralocorticoides y el 10,8% de los que no alcanzan la dosis objetivo. Del total de 2.693 pacientes ambulatorios con fraccion de eyeccion reducida, 291 (10,8%) no tenian registrada medicion de potasio. Durante el seguimiento, 179 de 1.431 (12,5%, IC95%, 10,8-14,3%) aumentaron su concentracion de potasio, aumento relacionado directamente con la edad, la diabetes mellitus y los antecedentes de ictus e inversamente con los antecedentes de hiperpotasemia. Conclusiones Este trabajo destaca el problema de la hiperpotasemia en pacientes con insuficiencia cardiaca de la practica clinica habitual y la necesidad de continuar y mejorar la vigilancia de este factor en estos pacientes por su interferencia en el tratamiento optimo.

Donation after circulatory death (DCD) represents a promising opportunity to overcome the relative shortage of donors for heart transplantation. However, the necessary period of warm ischemia is a concern. This study aims to determine the critical warm ischemia time based on in vivo biochemical changes. Sixteen DCD non-cardiac donors, without cardiovascular disease, underwent serial endomyocardial biopsies immediately before withdrawal of life-sustaining therapy (WLST), at circulatory arrest (CA) and every 2 min thereafter. Samples were processed into representative pools to assess calcium homeostasis, mitochondrial function and cellular viability. Compared to baseline, no significant deterioration was observed in any studied parameter at the time of CA (median: 9 min; IQR: 7-13 min; range: 4-19 min). Ten min after CA, phosphorylation of cAMP-dependent protein kinase-A on Thr197 and SERCA2 decreased markedly; and parallelly, mitochondrial complex II and IV activities decreased, and caspase 3/7 activity raised significantly. These results did not differ when donors with higher WLST to CA times (≥9 min) were analyzed separately. In human cardiomyocytes, the period from WLST to CA and the first 10 min after CA were not associated with a significant compromise in cellular function or viability. These findings may help to incorporate DCD into heart transplant programs. Fundación Mutua Madrileña. Sí

Altres ajuts: AstraZeneca Farmacéutica, Spain, S.A. (ESR-17-13244). Hyperkalaemia is a growing concern in the treatment of patients with heart failure and reduced ejection fraction (HFrEF) as it limits the use of some prognostic-modifying drugs and has a negative impact on prognosis. The objective of the present study was to estimate the prevalence of hyperkalaemia in outpatients with HFrEF and its impact on achieving optimal medical treatment. For this purpose, a multicentre, prospective, and observational study was carried out on consecutive HFrEF patients who were monitored as outpatients in heart failure (HF) units and who, in the opinion of their doctor, received optimal medical treatment. A total of 565 HFrEF patients were included from 16 specialised HF units. The mean age was 66 ± 12 years, 78% were male, 45% had an ischemic cause, 39% had atrial fibrillation, 43% were diabetic, 42% had a glomerular filtration rate < 60 mL/min/1.7 m, and the mean left ventricular ejection fraction was 31 ± 7%. Treatment at the study entry included: 76% on diuretics, 13% on ivabradine, 7% on digoxin, 18.9% on angiotensin-conversing enzyme inhibitors (ACEi), 11.3% on angiotensin receptors blockers (ARBs), 63.8% on angiotensin-neprilysin inhibitors (ARNi), 78.5% on mineralocorticoid receptor antagonists (MRAs), and 92.9% on beta-blockers. Potassium levels in the baseline analysis were: ≤5 mEq/L = 80.5%, 5.1-5.4 mEq/L = 13.8%, 5.5-5.9 mEq/L = 4.6%, and ≥6 mEq/L = 1.06%. Hyperkalaemia was the reason for not prescribing or reaching the target dose of an MRAs in 34.8% and 12.5% of patients, respectively. The impact of hyperkalaemia on not prescribing or dropping below the target dose in relation to ACEi, ARBs, and ARNi was significantly less. In conclusion, hyperkalaemia is a frequent problem in the management of patients with HFrEF and a limiting factor in the optimisation of medical treatment.

Background Cardiac resynchronization therapy (CRT) with biventricular pacing has demonstrated clinical benefits in heart failure patients with left bundle branch block (LBBB) and ventricular dysfunction. Left bundle branch area pacing (LBBAP) results in a relatively short QRS duration (QRSd) with fast left ventricular activation and could be considered as an alternative to conventional CRT. Purpose The aim of the present study was to evaluate the feasibility and outcomes of LBBAP in patients with indications for CRT. Methods Consecutive patients with indications for CRT were included. LBBAP was performed via transventricular septal approach (1–3). We aimed to achieve a paced QRS with right bundle branch conduction delay morphology, a stimulus to peak left ventricular activation time (S-LVAT) Results LBBAP was achieved in 19 of 21 (90.5%) patients with indication for CRT. Indications were heart failure with LBBB and left ventricular ejection fraction (LVEF) ≤35% in 8 (42%), AV node ablation or AV block with LVEF The mean follow-up was 4.6±1.7 months and the percentage of ventricular pacing was 93.4±13.9%. There were no device-related complications during this period. LBBA capture threshold was 0.6±0.3V at 0.4ms at the implantation, and remained stable (0.7±0.1 V, p=0.17). The lead impedance and R-wave amplitude at implantation were 636±106 ohms and 13.4±6.8 mV, and 541±88 ohms and 13.0±5.1 mV during the follow-up (p Mean S-LVAT was 85.5±13.9 ms, and mean QRSd was 122±9 ms, that remained stable during follow-up (122 vs 124 ms, p=0.21). In patients with LBBB, a significant narrowing of paced QRSd was achieved (160.9±16.7 vs. 123.9±9.7 ms, p Mean LVEF increased by 15.9%, from 35.4±8.9% at baseline to 51.3±9.8% at follow-up (p After one month, estimated time for elective replacement was 11.9±0.4 years. Conclusions LBBPA was successfully achieved in 90.5% of the patients with indication for CRT, with good and stable pacing electrical parameters, long estimated battery longevity and relatively narrow QRS, and was associated with improvement in cardiac function. LBBAP may be considered as a first-line option for patients with indications for CRT. Funding Acknowledgement Type of funding sources: None.

The severity of lung involvement is the main prognostic factor in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Carbohydrate antigen 15-3 (CA 15-3), a marker of lung damage and fibrosis, could help predict the prognosis of SARS-CoV-2 pneumonia. This was a retrospective and observational study. CA 15-3 was analyzed in the blood samples of patients consecutively admitted for SARS-CoV-2 pneumonia and whose blood samples were available in the biobank. Other prognostic markers were also measured (interleukin 6 [IL6], C-reactive protein [CRP], D-dimer, troponin T, and NT-ProBNP). The occurrence of in-hospital complications was registered, including death, the need for medical intensive care, and oxygen therapy at discharge. In this study, 539 patients were recruited (54.9% men, mean age: 59.6 ± 16.4 years). At admission, the mean concentrations of CA 15-3 was 20.5 ± 15.8 U/mL, and the concentration was correlated with male sex, older age, and other severity markers of coronavirus disease of 2019 (COVID-19) (IL6, CRP, D-dimer, troponine T, and NT-ProBNP). CA 15-3 levels were higher in patients who died (n = 56, 10.4%) (35.33 ± 30.45 vs. 18.8 ± 12.11, p p p = 0.011). Elevated CA 15-3 levels (above 34.5 U/mL) were a strong predictor of a complicated in-hospital course, in terms of a higher risk of death (adjusted odds ratio [OR] 3.74, 95% confidence interval [CI]: 1.22–11.9, p = 0.022) and need for intensive care (adjusted OR 4.56, 95% CI: 1.37–15.8) after adjusting for all other risk factors. The degree of lung damage and fibrosis evaluated in terms of CA 15-3 concentrations may allow early identification of the increased risk of complications in patients with SARS-CoV-2 pneumonia.

Aims Patients with heart failure (HF) and iron deficiency experience poor health-related quality of life (HRQoL). We evaluated the impact of intravenous (IV) ferric carboxymaltose (FCM) vs. placebo on HRQoL for the AFFIRM-AHF population. Methods and results The baseline 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), which was completed for 1058 (535 and 523) patients in the FCM and placebo groups, respectively, was administered prior to randomization and at Weeks 2, 4, 6, 12, 24, 36, and 52. The baseline KCCQ-12 overall summary score (OSS) mean ± standard error was 38.7 ± 0.9 (FCM group) and 37.1 ± 0.8 (placebo group); corresponding values for the clinical summary score (CSS) were 40.9 ± 0.9 and 40.1 ± 0.9. At Week 2, changes in OSS and CSS were similar for FCM and placebo. From Week 4 to Week 24, patients assigned to FCM had significantly greater improvements in OSS and CSS scores vs. placebo [adjusted mean difference (95% confidence interval, CI) at Week 4: 2.9 (0.5–5.3, P = 0.018) for OSS and 2.8 (0.3–5.3, P = 0.029) for CSS; adjusted mean difference (95% CI) at Week 24: 3.0 (0.3–5.6, P = 0.028) for OSS and 2.9 (0.2–5.6, P = 0.035) for CSS]. At Week 52, the treatment effect had attenuated but remained in favour of FCM. Conclusion In iron-deficient patients with HF and left ventricular ejection fraction, Graphical Abstract

Introduction and objectives To study the incidence, predictors and prognosis of follow-up de novo heart failure (HF) after discharge for acute myocardial infarction (AMI) in patients with left ventricular ejection fraction (LVEF) ≥ 50% and without previous history of HF. Methods Retrospective multicenter registry that includes 2158 consecutive patients discharged for AMI, from January 2011 to December 2015, with LVEF ≥ 50% and without history of HF. The association between clinical variables and the development of de novo HF was assessed by Fine–Gray proportional hazards regression analysis, accounting for death as a competing episode. The adjusted effect of post-discharge HF on subsequent mortality was investigated using extended Cox proportional hazards model. Results During follow-up (20.1 ± 11.8 months), 60 patients (2.8%) had HF admissions, with a cumulative incidence function of 1.7 per 100 patient-year. Age ≥ 70 years, hypertension, atrial fibrillation, and renal dysfunction were independent risk factors for follow-up HF. The HF incidence rate after surviving AMI increased with a higher number of risk factors, from 0.1% in patients with 0, to 1.8%, 3.8%, 15.3%, and 19% in patients with 1, 2, 3, and 4 risk factors, respectively (P Conclusions De novo HF after hospital discharge for ACS in patients with LVEF ≥ 50% is an independent predictor of follow-up death. Fortunately, it is an infrequent post-AMI complication and is easily predictable the combination of 4 clinical risk factors.

Identifying readmission predictors in heart failure (HF) patients may help guide preventative efforts and save costs. We aimed to identify 15- and 30-day readmission predictors due to cardiovascular reasons. A total of 1831 patients with acute HF admission were prospectively followed during a year. Patient-associated variables were gathered at admission/discharge and events during follow-up. A multivariate Fine and Gray competing risk regression model and a cumulative incidence function were used to identify predictors and build a risk score model for 15- and 30-day readmission. The 15- and 30-day readmission rates due to cardiovascular reasons were 7.1% and 13.9%. Previous acute myocardial infarction, congestive signs at discharge, and length of stay > 9 days were predictors of 15- and 30-day readmission, while much weight loss and large NT-ProBNP reduction were protective factors. The NT-ProBNP reduction was larger at 30 days (> 55%) vs 15 days (> 40%) to protect from readmission. Glomerular filtration rate at discharge 1 previous admissions due to HF were predictors of 30-day readmission, while first post-discharge control at an HF unit was a protective factor. Previous identified factors for early readmission were confirmed. The NT-ProBNP reduction should be increased (> 55%) to protect from 30-day readmission.

Resumen Introduccion y objetivos La enfermedad valvular en los pacientes con fibrilacion auricular incluidos en los ensayos clinicos con anticoagulantes orales directos (ACOD) es frecuente y se asocia con peor pronostico. El objetivo es evaluar la prevalencia de valvulopatia y su influencia en los eventos clinicos en la practica clinica real. Metodos Registro multicentrico retrospectivo que incluyo a 2.297 pacientes consecutivos con fibrilacion auricular no valvular que iniciaron tratamiento con ACOD entre enero de 2013 y diciembre de 2016. La enfermedad valvular se definio como afeccion moderada o grave. El evento principal fue la combinacion de muerte, ictus o accidente isquemico transitorio/embolia sistemica o hemorragia mayor. Se realizo un analisis de riesgos competitivos mediante un modelo de regresion de Fine y Gray, con la muerte como evento competitivo. Resultados Tenian valvulopatia 499 pacientes (21,7%), y la insuficiencia mitral fue la mas frecuente (13,7%). Los pacientes con valvulopatia eran de mas edad y con mayor comorbilidad. Tras el analisis multivariable, la enfermedad valvular fue predictora del evento combinado (HR = 1,54; IC95%, 1,22-1,94; p 0,05). Conclusiones En pacientes con fibrilacion auricular no valvular que inician tratamiento con ACOD, la enfermedad valvular es frecuente y se asocia con mayor riesgo de muerte, ictus o accidente isquemico transitorio/embolia sistemica o complicaciones hemorragicas. Estos hallazgos confirman los resultados de los ensayos clinicos y los expande al ambito de la practica clinica real.

Visual Abstract, Highlights • Using artificial intelligence, followed by in vivo validation, this study identified the key cardiac mechanism of action of empagliflozin in heart failure in patients with or without diabetes mellitus. • The most robust mechanism of action involved the NHE-1 co-transporter with 94.7% accuracy. • NHE-1 blockade by empagliflozin administration in rats restored the antiapoptotic activity of XIAP and BIRC5. • The beneficial reduction in cardiomyocyte cell death after empagliflozin treatment is independent of the presence of diabetes mellitus. • Empagliflozin could emerge as a new treatment for heart failure patients regardless of their glycemic status., Summary The mechanism of action of empagliflozin in heart failure with reduced ejection fraction (HFrEF) was deciphered using deep learning in silico analyses together with in vivo validation. The most robust mechanism of action involved the sodium-hydrogen exchanger (NHE)-1 co-transporter with 94.7% accuracy, which was similar for diabetics and nondiabetics. Notably, direct NHE1 blockade by empagliflozin ameliorated cardiomyocyte cell death by restoring expression of X-linked inhibitor of apoptosis (XIAP) and baculoviral IAP repeat-containing protein 5 (BIRC5). These results were independent of diabetes mellitus comorbidity, suggesting that empagliflozin may emerge as a new treatment in HFrEF.

High-sensitivity troponin T (hs-TnT) reflects the severity of ongoing myocardial damage. In acute heart failure (AHF), its additive prognostic value over B-type natriuretic peptides is unclear.Individual data of 1499 AHF patients with admission hs-TnT were collected from 3 cohorts.Patients (78 ± 10 years, 51% men, N-terminal fragment of pro-B-type natriuretic peptide - NT-proBNP - 5660 [2693-12,466], hs-TnT 43 ng/L [26-69]) experiencing in-hospital death (n = 187, 13%) had significantly higher hs-TnT and NT-proBNP on admission (both p 0.001). Patients with hs-TnT ≥43 ng/L and NT-proBNP ≥5660 ng/L had a 2.7-fold higher risk of in-hospital death (relative risk - RR 2.7, 95% confidence interval - CI 1.7-4.5). Among discharged patients, 1024 deaths (81%) occurred over 11 months (4-22). In the whole population, hs-TnT ≥43 ng/L predicted all-cause death at 6, 12 and 24 months independently from NT-proBNP ≥5660 ng/L. The best NT-proBNP cut-off for in-hospital mortality (4382 ng/L) independently predicted this endpoint, while the best hs-TnT cut-off (55 ng/L) did not. Patients with NT-proBNP ≥4382 ng/L and hs-TnT ≥55 ng/L had a 12-fold higher risk of in-hospital death (RR 11.7, 95% CI 6.9-19.7). The best hs-TnT cut-offs independently predicted all post-discharge outcomes.The best NT-proBNP cut-off (4382 ng/L) independently predicts outcome, while the best hs-TnT (55 ng/L) does not; patients with both biomarkers ≥best cut-offs have a 12-fold higher risk of in-hospital mortality. Admission hs-TnT ≥43 ng/L and the best hs-TnT cut-offs hold independent prognostic significance for post-discharge outcome, while hs-TnT seems less predictive than NT-proBNP when considering absolute values.

Beta-blockers are the cornerstone of treatment for various cardiovascular conditions. Although their effects have classically been considered to be driven by their antagonistic and competitive action on beta-adrenergic receptors, nowadays it is known that their effect goes beyond that of mere competition with catecholamines on these receptors. Beta-blockers were discovered as antianginal drugs in the 1960s and are currently widely used in heart failure, arrhythmias, and ischemic heart disease. In this article, we review the evidence for the beneficial effects of beta-blockers in these conditions, as well as the current recommendations in clinical practice guidelines for their use. Surprisingly, despite having been prescribed for more than 4 decades, new, previously unnoticed mechanisms of action on cellular compartments are still being discovered, which continues to open up new horizons for their use. All in all, beta-blockers are one of the most fascinating drug groups in our therapeutic armamentarium. B. Ibanez leads projects related to the subject of this review for the Spanish Society of Cardiology (2017 Translational Research Project) and the MICINN (Spanish Ministry of Science, Innovation, and Universities) through the Instituto de Salud Carlos III Health Research Fund (PI16/02110) and the European Regional Development Fund (ERDF: SAF2013-49663-EXP). The CNIC (National Center for Cardiovascular Research) is funded by the MICINN, the ISCiii, and the ProCNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Sí

Resumen Los bloqueadores beta son una piedra angular del tratamiento de diferentes enfermedades cardiovasculares. Si bien clasicamente se ha considerado que sus efectos se deben a su accion antagonica y competitiva en los receptores adrenergicos beta, hoy se conoce que su efecto va mas alla que el de un mero bloqueo de accion de las catecolaminas en estos receptores. Descubiertos como farmacos antianginosos en la decada de los sesenta, hoy se utilizan para diferentes enfermedades cardiovasculares, como la insuficiencia cardiaca, las arritmias y la cardiopatia isquemica. En este articulo se revisan las evidencias de los efectos beneficiosos de los bloqueadores beta en estas diferentes afecciones, asi como las recomendaciones actuales de su uso. Sorprendentemente, pese a utilizarse desde hace mas de 4 decadas, aun siguen descubriendose nuevos mecanismos de accion en compartimentos celulares no conocidos previamente, y esto hace que sigan abriendose nuevos horizontes para el uso de estos farmacos. En conjunto, son uno de los grupos mas fascinantes de nuestro arsenal terapeutico.

Resumen Introduccion y objetivos La evolucion tras una primera hospitalizacion por insuficiencia cardiaca (IC), en particular la interaccion entre supervivencia y rehospitalizaciones, no esta bien establecida. Metodos Se estudio a todos los pacientes con una primera hospitalizacion y diagnostico principal de IC en el periodo 2009-2013, mediante el analisis del Conjunto Minimo Basico de Datos en la Region de Murcia. Se diferencio entre pacientes nuevos o incidentes y recurrentes, y se calcularon tasas poblacionales y tendencias mediante regresion de joinpoint. Se realizo un seguimiento por tarjeta sanitaria individual hasta el fin de 2015, y se registraron la mortalidad y los reingresos, sus causas y la cronologia de los reingresos respecto al fallecimiento. Resultados Se identifico a 8.258 incidentes, con una tendencia creciente de la tasa anual (+2,3%; p Conclusiones La primera hospitalizacion por IC mantiene tasas en aumento, con elevada mortalidad y reingresos en el seguimiento, que se acumulan principalmente en el periodo previo al fallecimiento.

Resumen Introduccion En descompensaciones por insuficiencia cardiaca (IC), tanto el dano renal agudo (DRA) como los niveles elevados de galectina-3 (Gal-3) se han asociado con una peor evolucion. Los niveles plasmaticos de Gal-3 se ven influidos por la funcion renal; sin embargo, el posible papel de la Gal-3 como predictor de DRA no esta establecido. Metodos Se midieron las concentraciones de Gal-3 al ingreso en 175 pacientes hospitalizados por IC y se registro la aparicion de DRA segun los criterios analiticos RIFLE. Resultados Durante el ingreso, 44 pacientes (25,1%) desarrollaron DRA, aunque solo 14 (8%) correspondian a los estadios mas avanzados, siendo en estos los niveles de Gal-3 al ingreso significativamente mayores, permaneciendo como predictor de DRA tras el ajuste multivariado por otras variables predictoras y por funcion renal basal. Conclusiones Los valores elevados de Gal-3 al ingreso se asocian a mayor riesgo de DRA durante la hospitalizacion por IC descompensada.

Introduction In decompensated heart failure (HF), both acute kidney injury (AKI) and high Galectina-3 (Gal-3) levels have been associated with poorer outcomes. Plasma Gal-3 levels are affected by renal function; however, the potential role of Gal-3 as a predictor of AKI has not been established. Methods We measured Gal-3 concentrations at admission for 175 patients hospitalized for HF and recorded the onset of AKI according to the Risk, Injury, Failure, Loss and End-stage kidney disease (RIFLE) analytical criteria. Results During hospitalization, 44 patients (25.1%) developed AKI, although only 14 (8%) corresponded to more advanced stages. These 14 patients had significantly higher Gal-3 levels at admission, which remained a predictor of AKI after the multivariate adjustment by other predictors and by baseline renal function. Conclusions High Gal-3 levels at admission are associated with a higher risk of AKI during hospitalization for decompensated HF.