Search

José Ramón González-Juanatey,1 Josep Comín-Colet,2 Domingo Pascual Figal,3 Antoni Bayes-Genis,4 Jose Maria Cepeda,5 José M García-Pinilla,6,7 Antonio García-Quintana,8 Luis Manzano,9 Jose Luis Zamorano10 1Cardiology Department, Hospital Clínico Universitario Santiago de Compostela, Centro de investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Santiago de Compostela, Spain; 2Cardiology Department, Hospital Universitario de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain; 3Cardiology Department, Hospital Virgen de la Arrixaca, University of Murcia, Murcia, Spain; 4Cardiology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; 5Department of Internal Medicine, Hospital Vega Baja, Orihuela, Alicante, Spain; 6Cardiology Department, Hospital Universitario Virgen de la Victoria, IBIMA, Málaga, Spain; 7Department of Medicine and Dermatology, Universidad de Málaga, Málaga, Spain; 8Cardiology Department, Hospital Universitario de Gran Canaria Doctor Negrín, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain; 9Department of Internal Medicine, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Madrid, Spain; 10Cardiology Department, Hospital Universitario Ramón y Cajal, Madrid, SpainCorrespondence: José Ramón González-Juanatey, Email Jose.Ramon.Gonzalez.Juanatey@sergas.esAbstract: Heart failure (HF) is a progressive condition with periods of apparent stability and repeated worsening HF events. Over time, unless optimization of HF treatment, worsening HF events become more frequent and patients enter into a cycle of recurrent events with high morbidity and mortality. In patients with HF there is an activation of deleterious neurohormonal pathways, such as the renin angiotensin aldosterone system and the sympathetic system, and an inhibition of protective pathways, including natriuretic peptides and guanylate cyclase. Therefore, HF burden can be reduced only through a holistic approach that targets all neurohormonal systems. In this context, vericiguat may play a key role, as it is the only HF drug that activates the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate system. On the other hand, it has been described relevant disparities in the management of HF population. Consequently, it is necessary to homogenize the management of these patients, through an integrated patient-care pathway that should be adapted at the local level. In this context, the development of new technologies (ie, video call, specific platforms, remote control devices, etc.) may be very helpful. In this manuscript, a multidisciplinary group of experts analyzed the current evidence and shared their own experience to provide some recommendations about the therapeutic optimization of patients with recent worsening HF, with a particular focus on vericiguat, and also about how the integrated patient-care pathway should be performed.Keywords: heart failure, worsening heart failure, patient-care pathway, vericiguat

Damià Valero-Bover,1,2 David Monterde,2,3 Gerard Carot-Sans,1,2 Miguel Cainzos-Achirica,4,5 Josep Comin-Colet,6– 8 Emili Vela,1,2 Montse Clèries,1,2 Júlia Folguera,1,2 Sònia Abilleira,9 Miquel Arrufat,3 Yolanda Lejardi,3 Òscar Solans,2,10 Toni Dedeu,11 Marc Coca,1,2 Pol Pérez-Sust,1 Caridad Pontes,1,2,12 Jordi Piera-Jiménez1,2,13 1Catalan Health Service, Barcelona, Spain; 2Digitalization for the Sustainability of the Healthcare System (DS3) – Institut d’Investigacions Biomèdiques de Bellvitge (IDIBELL), Barcelona, Spain; 3Catalan Institute of Health, Barcelona, Spain; 4Center for Outcomes Research, Houston Methodist, Houston, TX, USA; 5Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medical Institutions, Baltimore, MD, USA; 6Cardiology Department, Bellvitge University Hospital (IDIBELL), Barcelona, Spain; 7Department of Medicine, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain; 8CIBER Cardiovascular (CIBERCV), L’Hospitalet de Llobregat, Barcelona, Spain; 9CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; 10Health Department, eHealth Unit, Barcelona, Spain; 11WHO European Centre for Primary Health Care, Almaty, Kazakhstan; 12Department of Pharmacology, Autonomous University of Barcelona, Barcelona, Spain; 13Faculty of Informatics, Telecommunications and Multimedia, Universitat Oberta de Catalunya, Barcelona, SpainCorrespondence: Jordi Piera-Jiménez, Catalan Health Service, Gran Via de les Corts Catalanes 587, Barcelona, 08007, Spain, Tel +34 93 403 85 85, Email jpiera@catsalut.catPurpose: To assess the contribution of age and comorbidity to the risk of critical illness in hospitalized COVID-19 patients using increasingly exhaustive tools for measuring comorbidity burden.Patients and Methods: We assessed the effect of age and comorbidity burden in a retrospective, multicenter cohort of patients hospitalized due to COVID-19 in Catalonia (North-East Spain) between March 1, 2020, and January 31, 2022. Vaccinated individuals and those admitted within the first of the six COVID-19 epidemic waves were excluded from the primary analysis but were included in secondary analyses. The primary outcome was critical illness, defined as the need for invasive mechanical ventilation, transfer to the intensive care unit (ICU), or in-hospital death. Explanatory variables included age, sex, and four summary measures of comorbidity burden on admission extracted from three indices: the Charlson index (17 diagnostic group codes), the Elixhauser index and count (31 diagnostic group codes), and the Queralt DxS index (3145 diagnostic group codes). All models were adjusted by wave and center. The proportion of the effect of age attributable to comorbidity burden was assessed using a causal mediation analysis.Results: The primary analysis included 10,551 hospitalizations due to COVID-19; of them, 3632 (34.4%) experienced critical illness. The frequency of critical illness increased with age and comorbidity burden on admission, irrespective of the measure used. In multivariate analyses, the effect size of age decreased with the number of diagnoses considered to estimate comorbidity burden. When adjusting for the Queralt DxS index, age showed a minimal contribution to critical illness; according to the causal mediation analysis, comorbidity burden on admission explained the 98.2% (95% CI 84.1– 117.1%) of the observed effect of age on critical illness.Conclusion: Comorbidity burden (when measured exhaustively) explains better than chronological age the increased risk of critical illness observed in patients hospitalized with COVID-19.Keywords: COVID-19, comorbidities, comorbidity burden, risk assessment, hospitalized patients, case-mix tool

David Monterde,1,2 Gerard Carot-Sans,2,3 Miguel Cainzos-Achirica,4,5 Sònia Abilleira,1,6 Marc Coca,2,3 Emili Vela,2,3 Montse Clèries,2,3 Damià Valero-Bover,2,3 Josep Comin-Colet,7– 9 Luis García-Eroles,2,3 Pol Pérez-Sust,3 Miquel Arrufat,1 Yolanda Lejardi,1 Jordi Piera-Jiménez2,3,10 1Catalan Institute of Health, Barcelona, Spain; 2Digitalization for the Sustainability of the Healthcare System (DS3), Sistema de Salut de Catalunya, Barcelona, Spain; 3Servei Català de la Salut, Barcelona, Spain; 4Center for Outcomes Research, Houston Methodist, Houston, TX, USA; 5Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medical Institutions, Baltimore, MD, USA; 6CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; 7Department of Cardiology, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain; 8Bioheart-Cardiovascular Diseases Research Group (Idibell), L’Hospitalet de Llobregat, Barcelona, Spain; 9Department of Clinical Sciences, School of Medicine, Universität de Barcelona - UB, L’Hospitalet de Llobregat, Barcelona, Spain; 10Open Evidence Research Group, Universitat Oberta de Catalunya, Barcelona, SpainCorrespondence: Jordi Piera-JiménezServei Català de la Salut (CatSalut), Travessera de les Corts, 131-159 (Edifici Olímpia), Barcelona, 08028, SpainTel +34 634283110Email jpiera@catsalut.catBackground: Comorbidity burden has been identified as a relevant predictor of critical illness in patients hospitalized with coronavirus disease 2019 (COVID-19). However, comorbidity burden is often represented by a simple count of few conditions that may not fully capture patients’ complexity.Purpose: To evaluate the performance of a comprehensive index of the comorbidity burden (Queralt DxS), which includes all chronic conditions present on admission, as an adjustment variable in models for predicting critical illness in hospitalized COVID-19 patients and compare it with two broadly used measures of comorbidity.Materials and Methods: We analyzed data from all COVID-19 hospitalizations reported in eight public hospitals in Catalonia (North-East Spain) between June 15 and December 8 2020. The primary outcome was a composite of critical illness that included the need for invasive mechanical ventilation, transfer to ICU, or in-hospital death. Predictors including age, sex, and comorbidities present on admission measured using three indices: the Charlson index, the Elixhauser index, and the Queralt DxS index for comorbidities on admission. The performance of different fitted models was compared using various indicators, including the area under the receiver operating characteristics curve (AUROCC).Results: Our analysis included 4607 hospitalized COVID-19 patients. Of them, 1315 experienced critical illness. Comorbidities significantly contributed to predicting the outcome in all summary indices used. AUC (95% CI) for prediction of critical illness was 0.641 (0.624– 0.660) for the Charlson index, 0.665 (0.645– 0.681) for the Elixhauser index, and 0.787 (0.773– 0.801) for the Queralt DxS index. Other metrics of model performance also showed Queralt DxS being consistently superior to the other indices.Conclusion: In our analysis, the ability of comorbidity indices to predict critical illness in hospitalized COVID-19 patients increased with their exhaustivity. The comprehensive Queralt DxS index may improve the accuracy of predictive models for resource allocation and clinical decision-making in the hospital setting.Keywords: comorbidity, multimorbidity, COVID-19, hospitalization, risk

Santiago Jiménez-Marrero,1,2 Miguel Cainzos-Achirica,1– 4 David Monterde,5 Luis Garcia-Eroles,5 Cristina Enjuanes,1,2 Sergi Yun,1,2,6 Alberto Garay,1,2 Pedro Moliner,1,2 Lidia Alcoberro,1,2 Xavier Corbella,2,6,7 Josep Comin-Colet1,2,8 1Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain; 2Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain; 3Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medical Institutions, Baltimore, MD, USA; 4School of Medicine and Health Sciences, International University of Catalonia, Barcelona, Spain; 5Healthcare Information and Knowledge Unit, Catalan Health Service, Barcelona, Spain; 6Department of Internal Medicine, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain; 7Hestia Chair in Integrated Health and Social Care, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain; 8Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, SpainCorrespondence: Josep Comin-ColetHospital Universitari de Bellvitge, Department of Cardiology, 19th Floor, Feixa Llarga s/n, 08907 Hospitalet de Llobregat, Barcelona, SpainTel +34932607078Email jcomin@bellvitgehospital.catBackground: The aims of the present analysis are to estimate the prevalence of five key chronic cardiovascular, metabolic and renal conditions at the population level, the prevalence of renin–angiotensin–aldosterone system inhibitor (RAASI) medication use and the magnitude of potassium (K+) derangements among RAASI users.Methods and Results: We used data from more than 375,000 individuals, 55 years of age or older, included in the population-based healthcare database of the Catalan Institute of Health between 2015 and 2017. The conditions of interest were chronic heart failure (CHF), chronic kidney disease (CKD), diabetes mellitus, ischemic heart disease and hypertension. RAASI medications included angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, mineralocorticoid receptor antagonists (MRAs) and renin inhibitors. Hyperkalemia was defined as K+ levels > 5.0 mEq/L and hypokalemia as K+ < 3.5 mEq/L. The prevalence of chronic cardiovascular, metabolic and renal conditions was high, and particularly that of hypertension (prevalence ranging from 48.2% to 48.9%). The use of at least one RAASI medication was almost ubiquitous in these patients (75.2– 77.3%). Among RAASI users, the frequency of K+ derangements, mainly of hyperkalemia, was very noticeable (12% overall), particularly in patients with CKD or CHF, elderly individuals and users of MRAs. Hypokalemia was less frequent (1%).Conclusion: The high prevalence of K+ derangements, and particularly hyperkalemia, among RAASI users highlights the real-world relevance of K+ derangements, and the importance of close monitoring and management of K+ levels in routine clinical practice. This is likely to benefit a large number of patients, particularly those at higher risk.Keywords: chronic heart failure, chronic kidney disease, heart failure, hyperkalemia, hypertension, potassium

David Monterde,1 Miguel Cainzos-Achirica,2,3 Yolima Cossio-Gil,4,5 Luis García-Eroles,6 Pol Pérez-Sust,7 Miquel Arrufat,1 Candela Calle,8 Josep Comin-Colet,3,9 César Velasco4,5 1Catalan Institute of Health, Barcelona, Spain; 2Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medical Institutions, Baltimore, MD, USA; 3Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain; 4Vall d’Hebron Hospital, Barcelona, Spain; 5Vall d’Hebron Research Institute (VHIR), Barcelona, Spain; 6Catalan Health Service, Barcelona, Spain; 7Catalan Health Department, Barcelona, Spain; 8Catalan Institute of Oncology (ICO), Barcelona, Spain; 9University of Barcelona, Barcelona, SpainCorrespondence: David MonterdeDepartment of Statistics, Information Systems, Catalan Institute of Health, Gran via De Les Corts Catalanes 587, Barcelona 08007, SpainTel +34 934824642Email dmonterde@gencat.catBackground: Accurate risk adjustment is crucial for healthcare management and benchmarking.Purpose: We aimed to compare the performance of classic comorbidity functions (Charlson’s and Elixhauser’s), of the All Patients Refined Diagnosis Related Groups (APR-DRG), and of the Queralt Indices, a family of novel, comprehensive comorbidity indices for the prediction of key clinical outcomes in hospitalized patients.Material and Methods: We conducted an observational, retrospective cohort study using administrative healthcare data from 156,459 hospital discharges in Catalonia (Spain) during 2018. Study outcomes were in-hospital death, long hospital stay, and intensive care unit (ICU) stay. We evaluated the performance of the following indices: Charlson’s and Elixhauser’s functions, Queralt’s Index for secondary hospital discharge diagnoses (Queralt DxS), the overall Queralt’s Index, which includes pre-existing comorbidities, in-hospital complications, and principal discharge diagnosis (Queralt Dx), and the APR-DRG. Discriminative ability was evaluated using the area under the curve (AUC), and measures of goodness of fit were also computed. Subgroup analyses were conducted by principal discharge diagnosis, by age, and type of admission.Results: Queralt DxS provided relevant risk adjustment information in a larger number of patients compared to Charlson’s and Elixhauser’s functions, and outperformed both for the prediction of the 3 study outcomes. Queralt Dx also outperformed Charlson’s and Elixhauser’s indices, and yielded superior predictive ability and goodness of fit compared to APR-DRG (AUC for in-hospital death 0.95 for Queralt Dx, 0.77– 0.93 for all other indices; for ICU stay 0.84 for Queralt Dx, 0.73– 0.83 for all other indices). The performance of Queralt DxS was at least as good as that of the APR-DRG in most principal discharge diagnosis subgroups.Conclusion: Our findings suggest that risk adjustment should go beyond pre-existing comorbidities and include principal discharge diagnoses and in-hospital complications. Validation of comprehensive risk adjustment tools such as the Queralt indices in other settings is needed.Keywords: benchmarking, case-mix, comorbidity, discrimination, multimorbidity, Queralt’s indices, risk

Olatz Urbina,1 Olivia Ferrández,1 Sònia Luque,1 Santiago Grau,1,2 Sergi Mojal,3 Rosa Pellicer,1 Marta Riu,4 Esther Salas,1 Josep Comin-Colet5 1Pharmacy Department, Hospital Universitari del Mar, Barcelona, Spain; 2Universitat Autònoma de Barcelona, Barcelona, Spain; 3Department of Statistics, Institut Hospital del Mar d’Investigacions Mèdiques, Barcelona, Spain; 4Department of Epidemiology and Health Services Evaluation, CIBER de Epidemiología y Salud Pública (CIBERESP), Hospital Universitari del Mar, Barcelona, Spain; 5Heart Failure Unit, Cardiology Department, Hospital Universitari del Mar, Barcelona, Spain Background: Because of the high incidence of drug-related problems (DRPs) among hospitalized patients with cardiovascular diseases and their potential impact on morbidity and mortality, it is important to identify the most susceptible patients, who therefore require closer monitoring of drug therapy.Purpose: To identify the profile of patients at higher risk of developing at least one DRP during hospitalization in a cardiology ward.Method: We consecutively included all patients hospitalized in the cardiology ward of a teaching hospital in 2009. DRPs were identified through a computerized warning system designed by the pharmacy department and integrated into the electronic medical record.Results: A total of 964 admissions were included, and at least one DRP was detected in 29.8%. The variables associated with a higher risk of these events were polypharmacy (odds ratio [OR]=1.228; 95% confidence interval [CI]=1.153–1.308), female sex (OR=1.496; 95% CI=1.026–2.180), and first admission (OR=1.494; 95% CI=1.005–2.221).Conclusion: Monitoring patients through a computerized warning system allowed the detection of at least one DRP in one-third of the patients. Knowledge of the risk factors for developing these problems in patients admitted to hospital for cardiovascular problems helps in identifying the most susceptible patients. Keywords: cardiovascular diseases, patient safety, drug therapy monitoring, computerized provider order entry, clinical pharmacist, pharmacy warning system

Aims: Combination of hypertonic saline solution (HSS) with intravenous loop diuretics has been suggested to improve diuretic response in patients hospitalized for heart failure (HF). The efficacy and safety of this approach in the ambulatory setting remain unexplored., Methods and Results: In this multicentre, double-blind, randomized study, we allocated ambulatory patients with worsening heart failure (WHF) to a 1-h infusion of intravenous furosemide ( iv Furosemide)-HSS versus iv Furosemide. The primary endpoint was the volume of diuresis at 3 h. Secondary endpoints included 3-h natriuresis and weight variation, 7-day congestion data, kidney function and electrolytes, and 30-day clinical events. Overall, 167 participants (median age: 81 years, 30.5% female) were randomized across 13 sites between December 2020 and March 2023. There were no differences in 3-h diuresis between treatments ( iv Furosemide-HSS: 1099 ml vs. iv Furosemide: 1103 ml, p = 0.963), 3-h natriuresis (∆ +2.642 mEq/L, p = 0.559), or 3-h weight (∆ +0.012 kg, p = 0.920). Patients in the iv Furosemide-HSS arm experienced significant weight decrease at 7 days (Δ -0.586 kg, p = 0.048). There were no between-treatment differences in clinical congestion score, biomarkers, inferior vena cava diameter, or the presence of lung ultrasound B-lines. At 30 days, 26.5% of the patients in the iv Furosemide-HSS group versus 33.3% in the iv Furosemide group experienced WHF (hazard ratio 0.76, p = 0.330). The incidence of death from any cause or HF hospitalization was 6% of patients in the iv Furosemide-HSS group and 8.3% of patients in the iv Furosemide group (hazard ratio 0.69, p = 0.521). The incidence of worsening kidney function or metabolic derangements was not significantly different in the two arms., Conclusions: A single infusion of iv Furosemide-HSS did not improve 3-h diuresis or congestion parameters in patients with ambulatory WHF. This therapy showed an appropriate safety profile., (© 2024 European Society of Cardiology.)

Background: Frequent monitoring of patients declined during the COVID-19 pandemic, harming patients with chronic diseases who critically needed correct monitoring. We evaluated the impact of the COVID-19 pandemic in patients with non-valvular atrial fibrillation (NVAF) receiving treatment with vitamin K antagonists (VKA) or non-vitamin K antagonist oral anticoagulants (NOAC) in clinical practice in Spain., Methods: This observational, retrospective study analyzed prevalent patients treated with NOAC/VKA on 14/03/2019 (pre-COVID-19 period) and 14/03/2020 (COVID-19 period), who were followed up to 12 months. The study also considered incident patients who started treatment with NOAC/VKA between 15/03/2019 and 13/03/2020 (pre-COVID-19 period) and from 15/03/2020 to 13/03/2021 (COVID-19 period). Demographic characteristics, comorbidities, effectiveness, treatment patterns, and healthcare resource utilization were considered., Results: Prevalent patients amounted to 12,336 and 13,342 patients, whereas 1,612 and 1,602 incident patients were included in the pre-COVID-19 and COVID-19 periods, respectively. Prevalent patients treated with VKA had more strokes, thromboembolism, and major bleeding compared to those receiving NOAC, particularly during the COVID-19 period. NOAC patients had a 12 % lower risk of death than those on treatment with VKA (Hazard ratio = 0.88 [95 % CI: 0.81 - 0.95], p = 0.033). In addition, VKA patients were less persistent after 12 months than NOAC patients (pre-COVID-19 period: 52.1 % vs. 78.9 %, p < 0.001; COVID-19 period: 49.2 % vs. 80.3 %, p < 0.001), and required more healthcare visits and hospitalizations than those on treatment with NOAC., Conclusion: Compared to VKA, NOAC seems to have reduced the incidence of severe events and the use of healthcare resources for NVAF, particularly during the pandemic., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ASM is an employee of Atrys Health SA, who was paid consultant to BMS in connection with this manuscript. DVL, JSM, MICA and AE are employees of Bristol Myers Squibb and have BMS stocks. JCC and ODS declare to have received fees as coordinator investigators of this study by Bristol Myers Squibb., (© 2024 The Authors.)

Cardiovascular disease is a common problem in cancer patients that is becoming more widely recognized. This may be a consequence of prior cardiovascular risk factors but could also be secondary to the anticancer treatments. With the goal of offering a multidisciplinary approach to guaranteeing optimal cancer therapy and the early detection of related cardiac diseases, and in light of the recent ESC Cardio-Oncology Guideline recommendations, we developed a Cardio-Oncology unit devoted to the prevention and management of these specific complications. This document brings together important aspects to consider for the development and organization of a Cardio-Oncology program through our own experience and the current evidence.

Aim: The LeoDOR trial explored the efficacy and safety of intermittent levosimendan therapy in the vulnerable phase following a hospitalization for acute heart failure (HF)., Methods and Results: In this prospective multicentre, double-blind, two-armed trial, patients with advanced HF were randomized 2:1 at the end of an index hospitalization for acute HF to intermittent levosimendan therapy or matching placebo for 12 weeks. All patients had left ventricular ejection fraction (LVEF) ≤30% during index hospitalization. Levosimendan was administered according to centre preference either as 6 h infusion at a rate of 0.2 μg/kg/min every 2 weeks, or as 24 h infusion at a rate of 0.1 μg/kg/min every 3 weeks. The primary efficacy assessment after 14 weeks was based on a global rank score consisting of three hierarchical groups. Secondary clinical endpoints included the composite risk of tiers 1 and 2 at 14 and 26 weeks, respectively. Due to the COVID-19 pandemic, the planned number of patients could not be recruited. The final modified intention-to-treat analysis included 145 patients (93 in the combined levosimendan arm, 52 in the placebo arm), which reduced the statistical power to detect a 20% risk reduction in the primary endpoint to 60%. Compared with placebo, intermittent levosimendan had no significant effect on the primary endpoint: the mean rank score was 72.55 for the levosimendan group versus 73.81 for the placebo group (p = 0.863). However, there was a signal towards a higher incidence of the individual clinical components of the primary endpoint in the levosimendan group versus the placebo group both after 14 weeks (hazard ratio [HR] 2.94, 95% confidence interval [CI] 1.12-7.68; p = 0.021) and 26 weeks (HR 1.64, 95% CI 0.87-3.11; p = 0.122)., Conclusions: Among patients recently hospitalized with HF and reduced LVEF, intermittent levosimendan therapy did not improve post-hospitalization clinical stability., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background ST-segment-elevation myocardial infarction complicated with no reflow after primary percutaneous coronary intervention is associated with adverse outcomes. Although several hyperemic drugs have been shown to improve the Thrombolysis in Myocardial Infarction flow, optimal treatment of no reflow remains unsettled. Saline infusion at 20 mL/min via a dedicated microcatheter causes (flow-mediated) hyperemia. The objective is to compare the efficacy of pharmacologic versus flow-mediated hyperemia in patients with ST-segment-elevation myocardial infarction complicated with no reflow. Methods and Results In the RAIN-FLOW (Treatment of Slow-Flow After Primary Percutaneous Coronary Intervention With Flow-Mediated Hyperemia) study, 67 patients with ST-segment-elevation myocardial infarction and no reflow were randomized to receive either pharmacologic-mediated hyperemia with intracoronary adenosine or nitroprusside (n=30) versus flow-mediated hyperemia (n=37). The angiographic corrected Thrombolysis in Myocardial Infarction frame count and the minimal microcirculatory resistance, as assessed with intracoronary pressure-thermistor wire, dedicated microcatheter, and thermodilution techniques, were compared after study interventions. Both Thrombolysis in Myocardial Infarction frame count(40.2±23.1 versus 39.2±20.7; P =0.858) and minimal microcirculatory resistance (753.6±661.5 versus 993.3±740.8 Wood units; P =0.174) were similar between groups. Thrombolysis in Myocardial Infarction 3 flow was observed in 26.7% versus 27.0% ( P =0.899). Flow-mediated hyperemia showed 2 different thermodilution patterns during saline infusion indicative of the severity of the no reflow phenomenon. In-hospital death and nonfatal heart failure were observed in 10.4% and 26.9%, respectively. Conclusions Both treatments showed similar (and limited) efficacy restoring coronary flow. Flow-mediated hyperemia with thermodilution pattern assessment allowed the simultaneous characterization of the no reflow degree and response to hyperemia. No reflow was associated with a high rate of adverse outcomes. Further research is warranted to prevent and to treat no reflow in patients with ST-segment-elevation myocardial infarction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04685941.

Aim: To compare the risk of ventricular arrhythmias (VA) and sudden death (SD) between New York Heart Association (NYHA) class I and NYHA class II-III patients with non-ischaemic cardiomyopathy (NICM)., Methods and Results: Observational retrospective cohort study including patients with NICM who underwent cardiac magnetic resonance at two hospitals. The primary endpoint included appropriate implantable cardioverter defibrillator (ICD) therapies, sustained ventricular tachycardia, resuscitated cardiac arrest and SD. The secondary endpoint included heart failure (HF) hospitalizations, heart transplant, left ventricular assist device implant or HF death. Overall, 698 patients were included, 33% in NYHA class I. During a median follow-up of 31 months, the primary endpoint occurred in 57 patients (8%), with no differences between NYHA class I and NYHA class II-III cases (7% vs. 9%, p = 0.62). Late gadolinium enhancement (LGE) was the only independent predictor of the primary outcome both in NYHA class I and NYHA class II-III patients. LGE+ NYHA class I patients had a similar cumulative incidence of the primary endpoint as compared to LGE+ NYHA class II-III (p = 0.92) and a significantly higher risk as compared to LGE- NYHA class II-III cases (p < 0.001). The risk of the secondary endpoint was significantly higher in patients in NYHA class II-III as compared to those in NYHA class I (hazard ratio 3.2, p = 0.001)., Conclusions: Patients with NICM in NYHA class I are not necessarily at low risk of VA and SD. Actually, LGE+ NYHA class I patients have a high risk. NYHA class I patients with high-risk factors, such as LGE, could benefit from primary prevention ICD at least as much as those in NYHA class II-III with the same risk factors., (© 2023 European Society of Cardiology.)

Background: Current guidelines recommend extending the use of dual antiplatelet therapy (DAPT) beyond 1 year in patients with an acute coronary syndrome (ACS) and a high risk of ischaemia and low risk of bleeding. No data exist about the implementation of this strategy in older adults from routine clinical practice., Methods: We conducted a Spanish multicentre, retrospective, observational registry-based study that included patients with ACS but no thrombotic or bleeding events during the first year of DAPT after discharge and no indication for oral anticoagulants. High bleeding risk was defined according to the Academic Research Consortium definition. We assessed the proportion of cases of extended DAPT among patients 65 ≥ years that went beyond 1 year after hospitalisation for ACS and the variables associated with the strategy., Results: We found that 48.1% (928/1,928) of patients were aged ≥ 65 years. DAPT was continued beyond 1 year in 32.1% (298/928) of patients ≥ 65; which was a similar proportion as with their younger counterparts. There was no significant correlation between a high bleeding risk and DAPT duration. Contrastingly, there was a strong correlation between the extent of coronary disease and DAPT duration (p < 0.001). Other variables associated with extended DAPT were a higher left ventricle ejection fraction, a history of heart failure and a prior stent thrombosis., Conclusion: There was no correlation between age and extended use of DAPT beyond 1 year in older patients with ACS. DAPT was extended in about one-third of patients ≥ 65 years. The severity of the coronary disease, prior heart failure, left ventricle ejection fraction and prior stent thrombosis all correlated with extended DAPT., (© 2023. The Author(s).)

Aims: This study aimed to assess, in patients with cardiogenic shock secondary to unprotected left main coronary artery-related myocardial infarction (ULMCA-related AMICS), the incidence and predictors of no recovery of left ventricular function during the admission., Methods and Results: This was an observational study conducted at two tertiary care centres (2012-20). The main outcome measured was death or requirement for heart transplantation (HT) or left ventricular assist devices (LVAD) during the admission. A total of 70 patients were included. Percutaneous coronary intervention (PCI) was successful in 53/70 patients (75.7%). The combined endpoint of death or requirement of HT or LVAD during the admission occurred in 41/70 patients (58.6%). The highest incidence of the primary endpoint was observed among patients with profound shock and occluded left main coronary artery (LMCA) (20/23, 87%, P < 0.001). Although a successful PCI reduced the incidence of the event in the whole cohort (51.9% vs. 82.4% in failed PCI, P = 0.026), this association was not observed among this last group of complex patients (86.7% vs. 87.5% in failed PCI, P = 0.731). The predictive model included left ventricular ejection fraction, baseline ULMCA Thrombolysis In Myocardial Infarction flow, and severity of shock and showed an optimal ability for predicting death or requirements for HT or LVAD during the admission (area under the curve 0.865, P < 0.001)., Conclusions: ULMCA-related AMICS was associated with a high in-hospital mortality or need for HT or LVAD. Prognosis was especially poor among patients with profound shock and baseline occluded LMCA, with a low probability of recovery regardless of successful PCI., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Non-ischaemic dilated cardiomyopathy (NIDCM) is characterized by left ventricular (LV) chamber enlargement and systolic dysfunction in the absence of coronary artery disease. Left ventricular reverse remodelling (LVRR) is the ability of a dilated ventricle to restore its normal size, shape and function. We sought to determine the frequency, clinical predictors and prognostic implications of LVRR, in a cohort of heart failure (HF) patients with NIDCM., Methods: We conducted a multicentre observational, retrospective cohort study of patients with NIDCM, with prospective serial echocardiography evaluations. LVRR was defined as an increase of ≥15% in left ventricular ejection fraction (LVEF) or as a LVEF increase ≥ 10% plus reduction of LV end-systolic diameter index ≥ 20%. We used multivariable logistic regression analyses to identify the baseline clinical predictors of LVRR and evaluate the prognostic impact of LVRR., Results: LVRR was achieved in 42.5% of 527 patients with NIDCM during the first year of follow-up (median LVEF 49%, median change +22%), Alcoholic aetiology, HF duration, baseline LVEF and the absence of LBBB (plus NT-proBNP levels when in the model), were the strongest predictors of LVRR. During a median follow-up of 47 months, 134 patients died (25.4%) and 7 patients (1.3%) received a heart transplant. Patients with LVRR presented better outcomes, regardless of other clinical conditions., Conclusions: In patients with NIDCM, LVRR was frequent and was associated with improved prognosis. Major clinical predictors of LVRR were alcoholic cardiomyopathy, absence of LBBB, shorter HF duration, and lower baseline LVEF and NT-proBNP levels. Our study advocates for clinical phenotyping of non-ischaemic dilated cardiomyopathy and intense gold-standard treatment optimization of patients according to current guidelines and recommendations in specialized HF units.

Acute hyperglycemia has been associated with worse prognosis in patients hospitalized for heart failure (HF). Nevertheless, studies evaluating the impact of glycemic control on long-term prognosis have shown conflicting results. Our aim was to assess the relationship between acute-to-chronic (A/C) glycemic ratio and 4-year mortality in a cohort of subjects hospitalized for acute HF. A total of 1062 subjects were consecutively included. We measured glycaemia at admission and estimated average chronic glucose levels and the A/C glycemic ratio were calculated. Subjects were stratified into groups according to the A/C glycemic ratio tertiles. The primary endpoint was 4-year mortality. Subjects with diabetes had higher risk for mortality compared to those without (HR 1.35 [95% CI: 1.10-1.65]; p = 0.004). A U-shape curve association was found between glucose at admission and mortality, with a HR of 1.60 [95% CI: 1.22-2.11]; p = 0.001, and a HR of 1.29 [95% CI: 0.97-1.70]; p = 0.078 for the first and the third tertile, respectively, in subjects with diabetes. Additionally, the A/C glycemic ratio was negatively associated with mortality (HR 0.76 [95% CI: 0.58-0.99]; p = 0.046 and HR 0.68 [95% CI: 0.52-0.89]; p = 0.005 for the second and third tertile, respectively). In multivariable analysis, the A/C glycemic ratio remained an independent predictor. In conclusion, in subjects hospitalized for acute HF, the A/C glycemic ratio is significantly associated with mortality, improving the ability to predict mortality compared with glucose levels at admission or average chronic glucose concentrations, especially in subjects with diabetes.

Background: Iron deficiency is a common disorder in patients with heart failure and is related with adverse outcomes and poor quality of life. Previous experimental studies have shown biological connections between iron homeostasis, mitochondrial metabolism, and myocardial function. However, the mechanisms involved in this crosstalk are yet to be unfolded., Methods: The present research attempts to investigate the intrinsic biological mechanisms between heart failure and iron deficiency and to identify potential prognostic biomarkers by determining the gene expression pattern in the blood of heart failure patients, using whole transcriptome and targeted TaqMan ® low-density array analyses., Results: We performed a stepwise cross-sectional longitudinal study in a cohort of chronic heart failure patients with and without systemic iron deficiency. First, the full transcriptome was performed in a nested case-control exploratory cohort of 7 paired patients and underscored 1128 differentially expressed transcripts according to iron status (cohort1#). Later, we analyzed the messenger RNA levels of 22 genes selected by their statistical significance and pathophysiological relevance, in a validation cohort of 71 patients (cohort 2#). Patients with systemic iron deficiency presented lower mRNA levels of mitochondrial ferritin, sirtuin-7, small integral membrane protein 20, adrenomedullin and endothelin converting enzyme-1. An intermediate mitochondrial ferritin gene expression and an intermediate or low sirtuin7 and small integral membrane protein 20 mRNA levels were associated with an increased risk of all-cause mortality and heart failure admission ((HR 2.40, 95% CI 1.04-5.50, p -value = 0.039), (HR 5.49, 95% CI 1.78-16.92, p -value = 0.003), (HR 9.51, 95% CI 2.69-33.53, p -value < 0.001), respectively)., Conclusions: Patients with chronic heart failure present different patterns of blood gene expression depending on systemic iron status that affect pivotal genes involved in iron regulation, mitochondrial metabolism, endothelial function and cardiovascular physiology, and correlate with adverse clinical outcomes.

Aims: Abnormal endogenous erythropoietin (EPO) constitutes an important cause of anaemia in chronic diseases. We analysed the relationships between iron deficiency (ID) and the adequacy of endogenous EPO in anaemic heart failure (HF) patients, and the impact of abnormal EPO on 12-month mortality., Methods and Results: We investigated 435 anaemic HF patients (age: 74 ± 10 years; males: 60%; New York Heart Association class I or II: 39%; left ventricular ejection fraction: 43 ± 17%). Patients with EPO higher than expected for a given haemoglobin were considered EPO-resistant whereas those with EPO lower than expected - EPO-deficient. ID was defined as serum ferritin <100 µg/L or 100-299 µg/L with transferrin saturation <20%. EPO-resistant patients (22%) had more advanced HF whereas those with EPO deficiency (57%) were more frequently females and had worse renal function. Lower serum ferritin (indicating depleted body iron stores) was related to higher EPO observed/predicted ratio when adjusted for significant clinical confounders, including C-reactive protein. One year all-cause mortality was 28% in patients with EPO resistance compared to 17% in patients with EPO deficiency and 10% in patients with adequate EPO (log-rank test for the comparison EPO resistance vs. adequate EPO: P = 0.02). When adjusted for other prognosticators, there was still a trend towards increased 12-month mortality in patients with higher EPO level., Conclusion: Anaemic HF patients with endogenous EPO deficiency vs. resistance have different clinical and laboratory characteristics. In such patients, ID contributes to EPO resistance independently of inflammation., (© 2021 European Society of Cardiology.)

MicroRNAs (miRNAs) participate in atrial remodeling and atrial fibrillation (AF) promotion. We determined the circulating miRNA profile in patients with AF and heart failure with reduced ejection fraction (HFrEF), and its potential role in promoting the arrhythmia. In plasma of 98 patients with HFrEF (49 with AF and 49 in sinus rhythm, SR), differential miRNA expression was determined by high-throughput microarray analysis followed by replication of selected candidates. Validated miRNAs were determined in human atrial samples, and potential arrhythmogenic mechanisms studied in HL-1 cells. Circulating miR-199a-5p and miR-22-5p were significantly increased in HFrEF patients with AF versus those with HFrEF in SR. Both miRNAs, but particularly miR-199a-5p, were increased in atrial samples of patients with AF. Overexpression of both miRNAs in HL-1 cells resulted in decreased protein levels of L-type Ca 2+ channel, NCX and connexin-40, leading to lower basal intracellular Ca 2+ levels, fewer inward currents, a moderate reduction in Ca 2+ buffering post-caffeine exposure, and a deficient cell-to-cell communication. In conclusion, circulating miR-199a-5p and miR-22-5p are higher in HFrEF patients with AF, with similar findings in human atrial samples of AF patients. Cells exposed to both miRNAs exhibited altered Ca 2+ handling and defective cell-to-cell communication, both findings being potential arrhythmogenic mechanisms.

Purpose: To determine the impact of non-cardiovascular comorbidities on the health-related quality of life (HRQoL) of patients with chronic heart failure (CHF)., Methods: A scoping review of the scientific literature published between 2009 and 2019 was carried out. Observational studies which assessed the HRQoL of patients with CHF using validated questionnaires and its association with non-cardiovascular comorbidities were included., Results: The search identified 1904 studies, of which 21 fulfilled the inclusion criteria to be included for analysis. HRQoL was measured through specific, generic, or both types of questionnaires in 72.2%, 16.7%, and 11.1% of the studies, respectively. The most common comorbidities studied were diabetes mellitus (12 studies), mental and behavioral disorders (8 studies), anemia and/or iron deficiency (7 studies), and respiratory diseases (6 studies). Across studies, 93 possible associations between non-cardiovascular comorbidities and HRQoL were tested, of which 21.5% regarded anemia or iron deficiency, 20.4% mental and behavioral disorders, 20.4% diabetes mellitus, and 14.0% respiratory diseases. Despite the large heterogeneity across studies, all 21 showed that the presence of a non-cardiovascular comorbidity had a negative impact on the HRQoL of patients with CHF. A statistically significant impact on worse HRQoL was found in 84.2% of associations between mental and behavioral disorders and HRQoL (patients with depression had up to 200% worse HRQoL than patients without depression); 73.7% of associations between diabetes mellitus and HRQoL (patients with diabetes mellitus had up to 21.8% worse HRQoL than patients without diabetes mellitus); 75% of associations between anemia and/or iron deficiency and HRQoL (patients with anemia and/or iron deficiency had up to 25.6% worse HRQoL than between patients without anemia and/or iron deficiency); and 61.5% of associations between respiratory diseases and HRQoL (patients with a respiratory disease had up to 21.3% worse HRQoL than patients without a respiratory disease)., Conclusion: The comprehensive management of patients with CHF should include the management of comorbidities which have been associated with a worse HRQoL, with special emphasis on anemia and iron deficiency, mental and behavioral disorders, diabetes mellitus, and respiratory diseases. An adequate control of these comorbidities may have a positive impact on the HRQoL of patients.

Previous studies have shown that heart failure is associated with worse health-related quality of life (HRQoL). The existence of differences according to gender remains controversial. We studied 1028 consecutive outpatients with heart failure and reduced ejection fraction (HFrEF) from a multicentre cross-sectional descriptive study across Spain that assessed HRQoL using two questionnaires (KCCQ, Kansas City Cardiomyopathy Questionnaire; and EQ-5D, EuroQoL 5 dimensions). The primary objective of the study was to describe differences in HRQoL between men and women in global scores and domains of health status of patients and explore gender differences and its interactions with heart failure related factors. In adjusted analysis women had lower scores in KCCQ overall summary scores when compared to men denoting worse HRQoL (54.7 ± 1.3 vs. 62.7 ± 0.8, p < 0.0001), and specifically got lower score in domains of symptom frequency, symptoms burden, physical limitation, quality of life and social limitation. No differences were found in domains of symptom stability and self-efficacy. Women also had lower scores on all items of EQ-5D (EQ-5D index 0.58 ± 0.01 vs. 0.67 ± 0.01, p < 0.0001). Finally, we analyzed interaction between gender and different clinical determinants regarding the presence of limitations in the 5Q-5D and overall summary score of KCCQ. Interestingly, there was no statistical significance for interaction for any variable. In conclusion, women with HFrEF have worse HRQoL compared to men. These differences do not appear to be mediated by clinical or biological factors classically associated with HRQoL nor with heart failure severity., Competing Interests: J.C.-C., M.A., F.F., L.A., M.C.-L. and L.M. received honoraries as members of the advisory committee of the VIDA-IC study. J.J.C. and T.F. are staff of the Medical Department of Pfizer S.L.U. and have collaborated in the development of the VIDA-IC study.

Background: Patient empowerment is a key factor in improving health outcomes., Objective: To evaluate the psychometric properties of the Spanish version of the questionnaire on Patient Empowerment in Long-Term Conditions (PELC) that evaluates the degree of empowerment of patients with chronic diseases., Methods: Three measurements were made (at baseline, 2 weeks and 12 weeks) of quality of life (QoL), self-care, self-efficacy and empowerment. Reliability was evaluated as internal consistency for the entire sample. Test-retest reproducibility was evaluated for patients who were stable from baseline to week 2 (n = 70). Validity was analysed (n = 124) as baseline correlations with QoL, self-care, self-efficacy, clinical data and psychosocial variables. Sensitivity to change was analysed in terms of effect size for patients who had improved between baseline and week 12 (n = 48)., Results: The study was carried out with 124 patients with a diagnosis of heart failure. Cronbach's alpha was high, at >0.9, and the interclass correlation coefficient was low, at 0.47. PELC questionnaire scores showed differences depending on New York Heart Association functional class (p<0.05) and, as posited in the a priori hypotheses, were moderately correlated with emotional dimensions of QoL (0.53) and self-efficacy (0.43). Effect size for the clinically improved subsample was moderate (0.67)., Conclusions: The results suggest that the Spanish version of the PELC questionnaire has appropriate psychometric properties in terms of internal consistency and validity and is low in terms of reproducibility and sensitivity to change., Competing Interests: The authors have declared that no competing interests exist.

The effects of iron deficiency (ID) have been widely studied in heart failure (HF) with reduced ejection fraction. On the other hand, studies in HF with preserved ejection fraction (HFpEF) are few and have included small numbers of participants. The aim of this study was to assess the role that ID plays in functional capacity and quality of life (QoL) in HFpEF while comparing several iron-related biomarkers to be used as potential predictors. ID was defined as ferritin <100 ng/mL or transferrin saturation <20%. Submaximal exercise capacity, measured by the 6-min walking test (6MWT), and QoL, assessed by the Minnesotta Living with Heart Failure Questionnaire (MLHFQ), were compared between iron deficient patients and patients with normal iron status. A total of 447 HFpEF patients were included in the present cross-sectional study, and ID prevalence was 73%. Patients with ID performed worse in the 6MWT compared to patients with normal iron status (ID 271 ± 94 m vs. non-ID 310 ± 108 m, p < 0.01). They also scored higher in the MLHFQ, denoting worse QoL (ID 49 ± 22 vs. non-ID 43 ± 23, p = 0.01). Regarding iron metabolism biomarkers, serum soluble transferrin receptor (sTfR) was the strongest independent predictor of functional capacity (β = -63, p < 0.0001, R 2 0.39) and QoL (β = 7.95, p < 0.0001, R 2 0.14) in multivariate models. This study postulates that ID is associated with worse functional capacity and QoL in HFpEF as well, and that sTfR is the best iron-related biomarker to predict both. Our study also suggests that the effects of ID could differ among HFpEF patients by left ventricular ejection fraction.

Background Intravenous ferric carboxymaltose (FCM) improves symptoms, functional capacity, and quality of life in heart failure and iron deficiency. The mechanisms underlying these effects are not fully understood. The aim of this study was to examine changes in myocardial iron content after FCM administration in patients with heart failure and iron deficiency using cardiac magnetic resonance. Methods and Results Fifty-three stable heart failure and iron deficiency patients were randomly assigned 1:1 to receive intravenous FCM or placebo in a multicenter, double-blind study. T2* and T1 mapping cardiac magnetic resonance sequences, noninvasive surrogates of intramyocardial iron, were evaluated before and 7 and 30 days after randomization using linear mixed regression analysis. Results are presented as least-square means with 95% CI. The primary end point was the change in T2* and T1 mapping at 7 and 30 days. Median age was 73 (65-78) years, with N-terminal pro-B-type natriuretic peptide, ferritin, and transferrin saturation medians of 1690 pg/mL (1010-2828), 63 ng/mL (22-114), and 15.7% (11.0-19.2), respectively. Baseline T2* and T1 mapping values did not significantly differ across treatment arms. On day 7, both T2* and T1 mapping (ms) were significantly lower in the FCM arm (36.6 [34.6-38.7] versus 40 [38-42.1], P =0.025; 1061 [1051-1072] versus 1085 [1074-1095], P =0.001, respectively). A similar reduction was found at 30 days for T2* (36.3 [34.1-38.5] versus 41.1 [38.9-43.4], P =0.003), but not for T1 mapping (1075 [1065-1085] versus 1079 [1069-1089], P =0.577). Conclusions In patients with heart failure and iron deficiency, FCM administration was associated with changes in the T2* and T1 mapping cardiac magnetic resonance sequences, indicative of myocardial iron repletion. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03398681.

Hospitalization for acute heart failure (HF) is associated with a substantial morbidity burden and with associated healthcare costs and an increased mortality risk. However, few if any major medical innovations have been witnessed in this area in recent times. Levosimendan is a first-in-class calcium sensitizer and potassium channel opener indicated for the management of acute HF. Experience in several clinical studies has indicated that administration of intravenous levosimendan in intermittent cycles may reduce hospitalization and mortality rates in patients with advanced HF; however, none of those trials were designed or powered to give conclusive insights into that possibility. This paper describes the rationale and protocol of LeoDOR (levosimendan infusions for patients with advanced chronic heart failure), a randomized, double-blind, placebo-controlled, international, multicentre trial that will explore the efficacy and safety of intermittent levosimendan therapy, in addition to optimized standard therapy, in patients following hospitalization for acute HF. Salient features of LeoDOR include the use of two treatment regimens, in order to evaluate the effects of different schedules and doses of levosimendan during a 12 week treatment phase, and the use of a global rank primary endpoint, in which all patients are ranked across three hierarchical groups ranging from time to death or urgent heart transplantation or implantation of a ventricular assist device to time to rehospitalization and, lastly, time-averaged proportional change in N-terminal pro-brain natriuretic peptide. Secondary endpoints include changes in HF symptoms and functional status at 14 weeks., (© 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: Iron deficiency (ID) in patients with chronic heart failure (CHF) is considered an adverse prognostic factor. We aimed to evaluate if ID in patients with CHF is associated with increased mortality and hospitalizations., Methods: We evaluated ID in patients with CHF at 3 university hospitals. ID was defined as absolute (ferritin < 100 μg/L) or functional (transferrin Saturation index < 20% and ferritin between 100 and 299 μg/L). We excluded patients who received treatment with intravenous Iron or Erythropoietin during follow-up. We evaluated if ID was a predictor of death or hospitalization due to heart failure or any cause using univariate and multivariate cox regression analysis., Results: We included 1684 patients, 65% males, 38% diabetics, median age of 72 years, 37% in functional class III-IV and 30% of patients with a left ventricular ejection fraction > 45%. Patients were well treated, with 87% and 88% of patients receiving renin-angiotensin inhibitors and beta-blockers, respectively. Median transferrin saturation index was 20%, median ferritin 155 ng/mL and median haemoglobin 13 g/dL. ID was present in 53% of patients; in 35% it was absolute and in 18% functional. Median follow-up was 20 months. ID was a predictor of death, hospitalization due to heart failure or to any cause in univariate analysis but not after multivariate analysis. No differences were found between absolute or functional ID regarding prognosis., Conclusion: In a real life population of patients with CHF and a high prevalence of heart failure with preserved ejection fraction, ID did not predict mortality or hospitalizations after adjustment for comorbidities, functional class and neurohormonal treatment.

Aims: The LION-HEART study was a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial evaluating the efficacy and safety of intravenous administration of intermittent doses of levosimendan in outpatients with advanced chronic heart failure., Methods and Results: Sixty-nine patients from 12 centres were randomly assigned at a 2:1 ratio to levosimendan or placebo groups, receiving treatment by a 6-hour intravenous infusion (0.2 μg/kg/min without bolus) every 2 weeks for 12 weeks. The primary endpoint was the effect on serum concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) throughout the treatment period in comparison with placebo. Secondary endpoints included evaluation of safety, clinical events and health-related quality of life (HRQoL). The area under the curve (AUC, pg.day/mL) of the levels of NT-proBNP over time for patients who received levosimendan was significantly lower than for the placebo group (344 × 10 3 [95% Confidence Interval (CI) 283 × 10 3 -404 × 10 3 ] vs. 535 × 10 3 [443 × 10 3 -626 × 10 3 ], p = 0.003). In comparison with the placebo group, the patients on levosimendan experienced a reduction in the rate of heart failure hospitalisation (hazard ratio 0.25; 95% CI 0.11-0.56; P = 0.001). Patients on levosimendan were less likely to experience a clinically significant decline in HRQoL over time (P = 0.022). Adverse event rates were similar in the two treatment groups., Conclusions: In this small pilot study, intermittent administration of levosimendan to ambulatory patients with advanced systolic heart failure reduced plasma concentrations of NT-proBNP, worsening of HRQoL and hospitalisation for heart failure. The efficacy and safety of this intervention should be confirmed in larger trials., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

Aims: To investigate the prevalence of iron deficiency (ID) in heart failure (HF) patients with normal vs. abnormal red cell indices (RCI), the associations between iron parameters and RCI, and prognostic consequences of ID independently of RCI., Methods and Results: We analysed clinical data of 1821 patients with HF [mean age 66 ± 13 years; 71% men; New York Heart Association class I/II/III/IV (11%/39%/44%/6%); left ventricular ejection fraction >45%: 19%]. Iron deficiency (ferritin <100 µg/L or ferritin 100-299 µg/L with transferrin saturation <20%) was common irrespective of the presence of anaemia (haemoglobin <12 g/dL in women and <13 g/dL in men) or low RCI, from 75% in anaemic subjects with low mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and MCH concentration (MCHC), to 36% in non-anaemic subjects with MCV, MCH, and MCHC above the lower limit of normal. After adjustment for clinical variables, iron parameters remained independently associated with haemoglobin, MCV, MCH, MCHC, mean reticulocyte haemoglobin content (CHR), and red cell distribution width (RDW). In multivariable Cox proportional hazard regression models there was a trend towards higher mortality in patients with vs. without ID when adjusted for relevant HF prognosticators and MCH or MCHC (but not haemoglobin, CHR or RDW)., Conclusions: Patients with HF should be routinely screened for ID irrespective of the presence of anaemia or abnormal RCI. The detrimental impact of ID on long-term survival in HF is partially independent of RCI., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

Background: Type 2 diabetes mellitus (T2DM) is strongly related to the in-hospital and short-term prognosis in patients with cardiovascular diseases needing surgical or invasive interventions. How T2DM might influence the treatment of aortic stenosis (AS) has not been completely elucidated for surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI). The aims of this study were: (1) to describe the use of aortic valve replacement procedures (TAVI and SAVR) among hospitalized patients with and without T2DM; and (2) to identify factors associated with in hospital mortality (IHM) among patients undergoing these procedures., Methods: We analyzed data from the Spanish National Hospital Discharge Database between January 1, 2014 and December 31, 2015 for patients aged ≥ 40 years. We selected patients whose medical procedures included TAVI (ICD-9-CM codes 35.05, 35.06) and SAVR (ICD-9-CM codes 35.21, 35.22). We stratified each cohort by diabetes status: T2DM (ICD-9-CM codes 250.x0, 250.x2) and no diabetes. We retrieved data about specific comorbidities, risk factors, procedures, and specific in-hospital postoperative complications. Hospital outcome variables included IHM, and length of hospital stay (LOHS)., Results: We identified a total of 2141 and 16,013 patients who underwent TAVI (n = 715; 33.39% with T2DM) and SAVR (n = 4057; 25.33% with T2DM). In patients who underwent TAVI we found no differences in IHM (3.64% in T2DM vs. 5.12% in non-T2DM, p = 0.603). In the cohort of SAVR, mean LOHS was significantly lower in patients with T2DM than in non-diabetic patients (13.77 vs. 17.27 days). IHM was lower in patients with T2DM (4.36% vs. 6.31%, p < 0.01). After multivariable adjustment for both procedures, patients with T2DM had significantly lower IHM than patients without diabetes (adjusted OR 0.60; IC 95% 0.37-0.99 for TAVI and adjusted OR 0.80; IC 95% 0.66-0-96 for SAVR)., Conclusions: T2DM diabetic patients with AS undergoing a valvular replacement procedure through SAVR or TAVI did not have a worse prognosis compared to non-diabetic patients during hospitalization, showing lower IHM after multivariable adjustment. However, given the limitations of administrative data more prospective studies and clinical trials aimed at evaluating the influence of these procedures in diabetic patients with AS are needed.

MicroRNAs (miRNAs) have emerged as promising biomarkers of disease. Their potential use in clinical practice requires standardized protocols with very low miRNA concentrations, particularly in plasma samples. Here we tested the most appropriate method for miRNA quantification and validated the performance of a hybridization platform using lower amounts of starting RNA. miRNAs isolated from human plasma and from a reference sample were quantified using four platforms and profiled with hybridization arrays and RNA sequencing (RNA-seq). Our results indicate that the Infinite ® 200 PRO Nanoquant and Nanodrop 2000 spectrophotometers magnified the miRNA concentration by detecting contaminants, proteins, and other forms of RNA. The Agilent 2100 Bioanalyzer PicoChip and SmallChip gave valuable information on RNA profile but were not a reliable quantification method for plasma samples. The Qubit ® 2.0 Fluorometer provided the most accurate quantification of miRNA content, although RNA-seq confirmed that only ~58% of small RNAs in plasma are true miRNAs. On the other hand, reducing the starting RNA to 70% of the recommended amount for miRNA profiling with arrays yielded results comparable to those obtained with the full amount, whereas a 50% reduction did not. These findings provide important clues for miRNA determination in human plasma samples.

Background: Heart failure (HF) is frequent and its prevalence is increasing. We aimed to evaluate the epidemiologic features of HF patients, the 1-year follow-up outcomes and the independent predictors of those outcomes at a population level., Methods and Results: Population-based longitudinal study including all prevalent HF cases in Catalonia (Spain) on December 31st, 2012. Patients were divided in 3 groups: patients without a previous HF hospitalization, patients with a remote (>1 year) HF hospitalization and patients with a recent (<1 year) HF admission. We analyzed 1year all-cause and HF hospitalizations, and all-cause mortality. Logistic regression was used to identify the independent predictors of each of those outcomes. A total of 88,195 patients were included. Mean age was 77 years, 55% were women. Comorbidities were frequent. Fourteen percent of patients had never been hospitalized, 71% had a remote HF hospitalization and 15% a recent hospitalization. At 1-year follow-up, all-cause and HF hospitalization were 53% and 8.8%, respectively. One-year all-cause mortality rate was 14%, and was higher in patients with a recent HF hospitalization (24%). The presence of diabetes mellitus, atrial fibrillation or chronic kidney disease was independently associated with all-cause and HF hospitalization and all-cause mortality. Hospital admissions and emergency department visits the previous year were also found to be independently associated with the three study outcomes., Conclusions: Outcomes are different depending on the HF population studied. Some comorbidity, an all-cause hospitalization or emergency department visit the previous year were associated with a worse outcome.

Aims: Heart failure (HF) is one of the diseases with greater healthcare expenditure. However, little is known about the cost of HF at a population level. Hence, our aim was to study the population-level distribution and predictors of healthcare expenditure in patients with HF., Methods and Results: This was a population-based longitudinal study including all prevalent HF cases in Catalonia (Spain) on 31 December 2012 (n = 88 195). We evaluated 1-year healthcare resource use and expenditure using the Health Department (CatSalut) surveillance system that collects detailed information on healthcare usage for the entire population. Mean age was 77.4 (12) years; 55% were women. One-year mortality rate was 14%. All-cause emergency department visits and unplanned hospitalizations were required at least once in 53.4% and 30.8% of patients, respectively. During 2013, a total of €536.2 million were spent in the care of HF patients (7.1% of the total healthcare budget). The main source of expenditure was hospitalization (39% of the total) whereas outpatient care represented 20% of the total expenditure. In the general population, outpatient care and hospitalization were the main expenses. In multivariate analysis, younger age, higher presence of co-morbidities, and a recent HF or all-cause hospitalization were independently associated with higher healthcare expenditure., Conclusions: In Catalonia, a large portion of the annual healthcare budget is devoted to HF patients. Unplanned hospitalization represents the main source of healthcare-related expenditure. The knowledge of how expenditure is distributed in a non-selected HF population might allow health providers to plan the distribution of resources in patients with HF., (© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.)

Background: Decisive information on the parameters involved in cognitive impairment in patients with chronic heart failure is as yet lacking. Our aim was to determine the functional and psychosocial variables related with cognitive impairment using the mini-mental-state examination (MMSE) with age-and education-corrected scores., Methods: A cohort study of chronic heart failure patients included in an integrated multidisciplinary hospital/primary care program. The MMSE (corrected for age and education in the Spanish population) was administered at enrolment in the program. Analyses were performed in 525 patients. Demographic and clinical variables were collected. Comprehensive assessment included depression (Yesavage), family function (family APGAR), social network (Duke), dependence (Barthel Index), frailty (Barber), and comorbidities. Univariate and multivariate logistic regression were performed to determine the predictors of cognitive impairment., Results: Cognitive impairment affected 145 patients (27.6 %). Explanatory factors were gender (OR: 2.77 (1.75-4.39) p < 0.001), ischemic etiology (OR: 1.99 (1.25-3.17) p = 0.004), frailty (OR: 1.58 (0.99 to 2.50, p =0.050), albumin > 3.5 (OR: 0.59 (0.35-0.99) p = 0.048), and beta-blocker treatment (OR: 0.36 (0.17 to 0.76, p = 0.007)). No association was found between cognitive impairment and social support or family function., Conclusion: The observed prevalence of cognitive impairment using MMSE corrected scores was 27.6 %. A global approach in the management of these patients is needed, especially focusing on women and patients with frailty, low albumin levels, and ischemic aetiology heart failure.