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Heart failure (HF) is a significant global concern, impacting patient morbidity, mortality, and healthcare costs. Guideline-directed medical therapy and various preventive measures have proven effective in improving clinical outcomes and reducing HF hospitalizations. Recent data indicates that remote HF monitoring facilitates early detection of HF decompensation by observing upstream events and parameters before clinical signs and symptoms manifest. Moreover, these innovative devices have been shown to decrease unnecessary HF hospitalizations and, in some cases, provide predictive insights before an actual HF incident. In this review, we aim to explore the data regarding smart scales and digital biomarkers and summarize both FDA-approved devices and emerging technologies by assessing their clinical utility, mechanism of HF decompensation detection, and ongoing trials. Furthermore, we also discuss the future trend of integrating these devices into routine clinical practice to improve patient clinical outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The effectiveness of complete revascularization is well established in patients with ST-segment elevation myocardial infarction (STEMI), but it is less investigated in those with non-ST-segment elevation myocardial infarction (NSTEMI)., Objectives: This study aimed to assess whether complete revascularization, compared with culprit-only revascularization, was associated with consistent outcomes in older patients with STEMI and NSTEMI., Methods: In the FIRE (Functional Assessment in Elderly MI Patients with Multivessel Disease) trial, 1,445 older patients with myocardial infarction (MI) were randomized to culprit-only or physiology-guided complete revascularization, stratified by STEMI (n = 256 culprit-only vs n = 253 complete) and NSTEMI (n = 469 culprit-only vs n = 467 complete). The primary outcome comprised a composite of death, MI, stroke, or revascularization at 1 year. The key secondary outcome included a composite of cardiovascular death or MI at 1 year., Results: In the overall study population, physiology-guided complete revascularization reduced both primary and key secondary outcomes. The primary outcome occurred in 54 (21.1%) STEMI patients randomized to culprit-only vs 41 (16.2%) STEMI patients of the complete group (HR: 0.75; 95% CI: 0.50-1.13) and in 98 (20.9%) NSTEMI patients randomized to culprit-only vs 72 (15.4%) NSTEMI patients of the complete group (HR: 0.71; 95% CI: 0.53-0.97), with negative interaction testing (P for interaction, 0.846). Similarly, no signal of heterogeneity with respect to the initial clinical presentation was observed for the key secondary endpoint (P for interaction, 0.654)., Conclusions: Physiology-guided complete revascularization, compared with culprit-only revascularization, provided consistent benefit across the whole spectrum of patients with MI. (FIRE [Functional Assessment in Elderly MI Patients With Multivessel Disease]; NCT03772743)., Competing Interests: Funding Support and Author Disclosures Sahajanand Medical Technologies Ltd (SMT), Medis Medical Imaging Systems, Eukon S.r.l., Siemens Healthineers, General Electric (GE) Healthcare, and Insight Lifetech provided unrestricted funding to the study sponsor for the conduction of the trial. These companies had no involvement in the trial design, data collection, analysis, interpretation, or writing of the manuscript. Dr Campo has received research grants and personal fees from Abbott Vascular, GADA, Menarini, Amgen, Daichi-Sankyo, and Sanofi, outside the submitted work. Dr Moreno has received speaker/consulting fees from Abbott Vascular, AMGEN, AstraZeneca, Biosensors, Biotronik, Boston Scientific, Daiichi-Sankyo, Edwards, Medtronic, and Philips, outside the submitted work. Dr Biscaglia has received funding from the Italian Health Minister (Ricerca Finalizzata 2021, GR-2021-12372516) for the conduction of the Functional Coronary Angiography Guided Revascularization in STEMI trial; and has received personal fees from Abbott Vascularand Siemens Healthcare, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Over the past five decades, the Fontan procedure has been developed to improve the life expectancy of patients with congenital heart defects characterized by a functionally single ventricle. The Fontan circulation aims at redirecting systemic venous return to the pulmonary circulation in the absence of an impelling subpulmonary ventricle, which makes this physiology quite fragile and leads to several long-term complications. Despite the importance of hemodynamic assessment through cardiac catheterization in the management and follow-up of these patients, a thorough understanding of the ultimate functioning of this type of circulation is lacking, and the interpretation of the hemodynamic data is often complex. In recent years, new tools such as combined catheterization with cardiopulmonary exercise testing have been incorporated to improve the understanding of the hemodynamic profile of these patients. Furthermore, extensive percutaneous treatment options have been developed, addressing issues ranging from obstructive problems in Fontan pathway and acquired shunts through compensatory collaterals to the percutaneous treatment of lymphatic circulation disorders and transcatheter edge-to-edge repair of atrioventricular valves. The aim of this review is to detail the various tools used in cardiac catheterization for patients with Fontan circulation, analyze different percutaneous treatment strategies, and discuss the latest advancements in this field.

Background: The results of most school-based health promotion initiatives are inconclusive., Objectives: This trial assessed the effect of time-varying exposures to a multicomponent school-based health promotion intervention (SI! Program) on adiposity markers., Methods: A total of 48 schools in Madrid (Spain) were cluster randomized to receive the SI! Program through elementary education grades 1 to 6 (E1-6, 12 schools, 459 children), 1 to 3 (E1-3, 12 schools, 513 children), or 4 to 6 (E4-6, 12 schools, 419 children) or to receive the standard curriculum (control, 12 schools, 379 children). The primary endpoint was the between-group difference at 3- and 6-year follow-up in the change from baseline in adiposity markers and the overall knowledge-attitudes-habits (KAH) score., Results: At 3-year follow-up, children who had the intervention showed significantly lower increases than the control group in z-scores for body mass index (BMI), waist-to-height ratio (WHtR), and waist circumference (WC) (zBMI: -0.09; 95% CI: -0.16 to -0.03; P = 0.003; zWC and zWHtR: -0.19; 95% CI: -0.28 to -0.10; P < 0.001). At 6-year follow-up, the beneficial trend in zWC and zWHtR was maintained in the E1-6 and E1-3 groups: difference zWC control vs E1-6 (-0.19; 95% CI: -0.36 to -0.03; P = 0.020), control vs E1-3 (-0.22; 95% CI: -0.38 to -0.06; P = 0.009); difference zWHtR control vs E1-6 (-0.24; 95% CI: -0.41 to -0.06; P = 0.009), and control vs E1-3 (-0.29; 95% CI: -0.47 to -0.11; P = 0.001). No significant between-group differences were found in the change of overall KAH score., Conclusions: Early elementary school interventions may be more effective than later interventions on abdominal adiposity. Further research should assess the sustainability effects of school-based health promotion programs., Competing Interests: Funding Support and Author Disclosures The study was supported by the SHE Foundation-la Caixa Foundation under agreement LCF/PR/CE16/10700001. Mr Martínez-Gómez is the recipient of grant FPU21/04891 (Ayudas para la formación de profesorado universitario, FPU-2021) from the Ministry of Education, Cluture, and Sport. Dr Fernández-Jiménez is the recipient of grant PI22/01560 from the Carlos III Institute of Health (Instituto de Salud Carlos III [ISCIII]) with cofunding from the European Union. The National Center for Cardiovascular Research (Centro Nacional de Investigaciones Cardiovasculares [CNIC]) is supported by the ISCIII, the Ministry of Science, Innovation, and Universities (MCIUN), and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Hypereosinophilic syndrome can produce cardiac involvement and endomyocardial fibrosis, which have a poor prognosis. However, there is limited information regarding cardiac involvement among migrants from Latin America with eosinophilia related to helminthiasis., Methods: We conducted a pilot observational study where an echocardiography was performed on migrants from Latin America with both eosinophilia (>450 cells/μL) and a diagnosis of helminth infection, and on migrants from Latin America without eosinophilia or helminth infection. Microbiological techniques included a stool microscopic examination using the Ritchie's formalin-ether technique, and a specific serology to detect Strongyloides stercoralis antibodies., Results: 37 participants were included, 20 with eosinophilia and 17 without eosinophilia. Twenty (54.1%) were men with a mean age of 41.3 (SD 14.3) years. Helminthic infections diagnosed in the group with eosinophilia were: 17 cases of S. stercoralis infection, 1 case of hookworm infection, and 2 cases of S. stercoralis and hookworm coinfection. Among participants with eosinophilia, echocardiographic findings revealed a greater right ventricle thickness (p = 0.001) and left atrial area and volume index (p = 0.003 and p = 0.004, respectively), while showing a lower left atrial strain (p = 0.006) and E-wave deceleration time (p = 0.008). An increase was shown in both posterior and anterior mitral leaflet thickness (p = 0.0014 and p = 0.004, respectively) when compared with participants without eosinophilia., Conclusions: Migrants from Latin America with eosinophilia related to helminthic infections might present incipient echocardiographic alterations suggestive of early diastolic dysfunction, that could be related to eosinophilia-induced changes in the endomyocardium., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sempere et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This study aimed to determine the prevalence of non-adherence to preventive interventions, its clinical consequences, and factors associated with non-adherence to secondary prevention measures, with a special emphasis on sex and gender., Methods: Prospective observational study of patients hospitalized for acute myocardial infarction (AMI) in whom an evaluation of adherence to medication, Mediterranean diet, physical activity, and cardiac rehabilitation was performed after 6 and 12 months, with systematic assessment of predictors including patient-, disease-, psychological-, social-, and gender-related factors using self-administered questionnaires., Results: Of 503 patients included, 101 (20,1%) were females. At one year, 85% of patients did not adhere to at least one of the recommendations with no differences between females and males. However, two factors more frequent in females, caregiver burden (adjusted OR, 1.45; 95%CI, 1.08-1.94) and depressive symptoms (adjusted OR, 1.40; 95%CI, 1.03-1.92) predicted non-adherence to all measures together. Chronic kidney disease (aOR, 3.24; 95%CI, 1.02-10.48) and being female (aOR, 2.21; 95%CI, 1.18-4.13) were associated with non-adherence to the Mediterranean diet; diabetes with organ damage (aOR, 12.06; 95%CI, 1.93-7.69) and older age (aOR, 0.96 per year; 95%CI, 0.93-0.99), among others, with physical activity; and higher body mass index with cardiac rehabilitation participation (aOR, 1.07; 95%CI, 1.002-1.14) and completion (aOR, 1.14; 95%CI, 1.03-1.26)., Conclusion: Adherence to all secondary prevention measures after AMI remains very low and is associated with several gender-related factors. Multidisciplinary intervention strategies targeting the most vulnerable patient groups, such as females or patients with diabetes, obesity, chronic kidney disease, or depression, are warranted., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hector Bueno reports financial support was provided by Spanish Society of Cardiology. Hector Bueno reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory and funding grants. Hector Bueno reports a relationship with Janssen Pharmaceuticals Inc that includes: consulting or advisory and funding grants. Hector Bueno reports a relationship with Novartis Pharmaceuticals Corporation that includes: consulting or advisory and funding grants. Hector Bueno reports a relationship with Bayer Pharma AG that includes: consulting or advisory. Lourdes Vicent reports a relationship with Carlos III Health Institute that includes: funding grants. Nicolas Rosillo reports a relationship with Carlos III Health Institute that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Congestive nephropathy is an underappreciated manifestation of cardiorenal syndrome and is characterized by a potentially reversible kidney dysfunction caused by a reduced renal venous outflow secondary to right-sided heart failure or intra-abdominal hypertension. To date, the histological diagnostic criteria for congestive nephropathy have not been defined. We herein report a case of acute renal dysfunction following cardiac allograft failure and present a review of the relevant literature to elucidate the current understanding of the disease. Our case demonstrated that congestion-driven nephropathy may be histopathologically characterized by markedly dilated veins and peritubular capillaries, focally accentuated low-grade acute tubular damage, small areas of interstitial fibrosis, and tubular atrophy on a background of normal glomeruli and predominantly normal tubular cell differentiation., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Purpose of Review: Diuretics are the cornerstone therapy for acute heart failure (HF) and congestion. Patients chronically exposed to loop diuretics may develop diuretic resistance as a consequence of nephron remodelling, and the combination of diuretics will be necessary to improve diuretic response and achieve decongestion. This review integrates data from recent research and offers a practical approach to current pharmacologic therapies to manage congestion in HF with a focus on combinational therapy., Recent Findings: Until recently, combined diuretic treatment was based on observational studies and expert opinion. Recent evidence from clinical trials has shown that combined diuretic treatment can be started earlier without escalating the doses of loop diuretics with an adequate safety profile. Diuretic combination is a promising strategy for overcoming diuretic resistance in HF. Further studies aiming to get more insights into the pathophysiology of diuretic resistance and large clinical trials confirming the safety and efficacy over standard diuretics regimens are warranted., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Lymphoid tumor patients often exhibit resistance to standard therapies or experience relapse post-remission. Relapse is driven by Tumor Initiating Cells (TICs), a subset of tumor cells capable of regrowing the tumor and highly resistant to therapy. Growing cells in 3D gels is a method to discern tumorigenic cells because it strongly correlates with tumorigenicity. The finding that TICs, rather than differentiated tumor cells, grow in 3D gels offers a unique opportunity to unveil TIC-specific signaling pathways and therapeutic targets common to various cancer types. Here, we show that culturing lymphoid cells in 3D gels triggers reactive oxygen species (ROS) production, leading to non-tumor lymphoid cell death while enabling the survival and proliferation of a subset of lymphoma/leukemia cells, TICs or TIC-like cells. Treatment with the antioxidant N-acetylcysteine inhibits this lethality and promotes the growth of primary non-tumor lymphoid cells in 3D gels. A subset of lymphoma cells, characterized by an increased abundance of the antioxidant glutathione, escape ROS-induced lethality, a response not seen in non-tumor cells. Reducing glutathione production in lymphoma cells, either through pharmacological inhibition of glutamate cysteine ligase (GCL), the enzyme catalyzing the rate-limiting step in glutathione biosynthesis, or via knockdown of GCLC, the GCL catalytic subunit, sharply decreased cell growth in 3D gels and xenografts. Tumor cells from B-cell lymphoma/leukemia patients and λ-MYC mice, a B-cell lymphoma mouse model, overproduce glutathione. Importantly, pharmacological GCL inhibition hindered lymphoma growth in female λ-MYC mice, suggesting that this treatment holds promise as a therapeutic strategy for female lymphoma/leukemia patients., (© 2024. The Author(s).)

The oxidative phosphorylation (OXPHOS) system is intricately organized, with respiratory complexes forming super-assembled quaternary structures whose assembly mechanisms and physiological roles remain under investigation. Cox7a2l, also known as Scaf1, facilitates complex III and complex IV (CIII-CIV) super-assembly, enhancing energetic efficiency in various species. We examined the role of Cox7a1, another Cox7a family member, in supercomplex assembly and muscle physiology. Zebrafish lacking Cox7a1 exhibited reduced CIV 2 formation, metabolic alterations, and non-pathological muscle performance decline. Additionally, cox7a1 -/- hearts displayed a pro-regenerative metabolic profile, impacting cardiac regenerative response. The distinct phenotypic effects of cox7a1 -/- and cox7a2l -/- underscore the diverse metabolic and physiological consequences of impaired supercomplex formation, emphasizing the significance of Cox7a1 in muscle maturation within the OXPHOS system., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Carbohydrate antigen 125 (CA125) is a proteolytic fragment of MUC-16 that is increased in heart failure (HF) and associated with inflammation, fluid overload, and worse adverse events. Our main objective was to study the expression of CA125 on epicardium and its association with inflammation, adipogenesis, and fibrosis., Methods: Epicardial fat biopsies and blood were obtained from 151 non-selected patients undergoing open heart surgery. Immunohistochemistry, ELISA, or real-time PCR were used for analyzing protein or mRNA expression levels of CA125 and markers of inflammatory cells, fibroblasts, and adipocytes. Epithelial or stromal cells from epicardium were isolated and cultured to identify CA125 and its association with the adipogenesis and fibrosis pathways, respectively., Results: The median age was 71 (63-74) years, 106 patients (70%) were male, and 62 (41%) had an established diagnosis of HF before surgery. The slice of epicardial fat biopsy determined a positive and colorimetric staining on the epithelial layer after incubating with the CA125 M11 antibody, providing the first description of CA125 expression in the human epicardium. Epicardial CA125 showed a strong and positive correlation with markers of inflammation and fibrosis in the epicardial fat tissue while exhibiting a negative correlation with markers of the adipogenesis pathway. This relationship remained significant after adjusting for potential confounders such as a prior HF diagnosis and plasma CA125 levels., Conclusion: Epicardial cells express CA125, which is positively associated with inflammatory and fibroblast markers in epicardial adipose tissue. These results suggest that CA125 may be biologically involved in HF progression (transition from adipogenesis to fibrosis)., (© 2024. The Author(s).)

Most of the signs and symptoms of heart failure can be explained by fluid overload, which is also related to disease progression. Fluid overload is a complex phenomenon that extends beyond increased intravascular pressures and poses challenges for accurate diagnosis and effective treatment. Current recommendations advise a multiparametric approach, including clinical data (symptoms/signs), imaging tests, and biomarkers. This article proposes a practical therapeutic approach to managing hydrosaline overload in heart failure in both inpatient and outpatient settings. This document is an initiative of the Spanish Society of Internal Medicine (SEMI) in collaboration with the Spanish Society of Cardiology (SEC) and the Spanish Society of Nephrology (S.E.N.)., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Percutaneous mitral paravalvular leak (PVL) closure techniques are an effective and safe alternative to surgical treatment, but data regarding long-term outcomes are scarce. We aim to describe the impact of successful percutaneous mitral PVL closure on long-term outcomes., Methods: All consecutive patients in whom a first-attempt percutaneous mitral PVL closure was performed in a single tertiary centre between January 2010 and October 2021 were included. Clinical variables, procedural details, and procedural success were collected. Patients were classified based on procedural success, defined as no more than mild residual leak. All-cause mortality was the primary endpoint. Cardiovascular death and heart failure hospitalizations (HFHs) were key secondary endpoints., Results: Ninety patients (median age 72.5 years [66.0-78.4]; median EuroSCORE-II 8.2 [5.3-12.46]) were included. Although reduction of at least 1 degree in PVL severity was achieved in 82 (91.1%), procedural success was achieved in 47 (52.2%). Chronic kidney disease, previous surgery for PVL, and the presence of multiple jets were independently associated with procedural failure. After a median follow-up of 3.2 (1.2-5.2) years, mortality rate was higher in the procedural failure group (27.3 per 100 patients-years) compared with the group with successful closure (8.2 per 100 patient-years). Procedural failure was associated with all-cause death (adjusted hazard ratio [aHR], 2.59; 95% confidence interval [CI], 1.41-4.78), cardiovascular death (aHR, 3.53; 95% CI, 1.67-7.49) and HFH (aHR, 3.27; 95% CI,1.72-6.20)., Conclusions: A successful reduction in PVL to mild or absent is associated with improved rates of all-cause death, cardiovascular death, and HFHs., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: In arrhythmogenic right ventricular cardiomyopathy (ARVC) non-invasive scar evaluation is not included among the diagnostic criteria or the predictors of ventricular arrhythmias (VA) and sudden death (SD). Computed tomography (CT) has excellent spatial resolution and allows a clear distinction between myocardium and fat; thus, it has great potential for the evaluation of myocardial scar in ARVC. Objective: The objective of this study is to evaluate the feasibility, and the diagnostic and prognostic value of semi-automated quantification of right ventricular (RV) fat replacement from CT images. Methods: An observational case-control study was carried out including 23 patients with a definite (19) or borderline (4) ARVC diagnosis and 23 age- and sex-matched controls without structural heart disease. All patients underwent contrast-enhanced cardiac CT. RV images were semi-automatically reconstructed with the ADAS-3D software (ADAS3D Medical, Barcelona, Spain). A fibrofatty scar was defined as values of Hounsfield Units (HU) <-10. Within the scar, a border zone (between -10 HU and -50 HU) and dense scar (<-50 HU) were distinguished. Results: All ARVC patients had an RV scar and all scar-related measurements were significantly higher in ARVC cases than in controls ( p < 0.001). The total scar area and dense scar area showed no overlapping values between cases and controls, achieving perfect diagnostic performance (sensitivity and specificity of 100%). Among ARVC patients, 16 (70%) had experienced sustained VA or aborted SD. Among all clinical, ECG and imaging parameters, the dense scar area was the only one with a statistically significant association with VA and SD ( p = 0.003). Conclusions: In ARVC, RV myocardial fat quantification from CT is feasible and may have considerable diagnostic and prognostic value.

Background: Desmin (DES) pathogenic variants cause a small proportion of arrhythmogenic cardiomyopathy (ACM). Outcomes data on DES-related ACM are scarce., Objectives: This study sought to provide information on the clinical phenotype and outcomes of patients with ACM caused by pathogenic variants of the DES gene in a multicenter cohort., Methods: We collected phenotypic and outcomes data from 16 families with DES-related ACM from 10 European centers. We assessed in vitro DES aggregates. Major cardiac events were compared to historical controls with lamin A/C truncating variant (LMNA-tv) and filament C truncating variant (FLNC-tv) ACM., Results: Of 82 patients (54% males, median age: 36 years), 11 experienced sudden cardiac death (SCD) (n = 7) or heart failure death (HFd)/heart transplantation (HTx) (n = 4) before clinical evaluation. Among 68 survivors, 59 (86%) presented signs of cardiomyopathy, with left ventricular (LV) dominant (50%) or biventricular (34%) disease. Mean LV ejection fraction was 51% ± 13%; 36 of 53 had late gadolinium enhancement (ring-like pattern in 49%). During a median of 6.73 years (Q1-Q3: 3.55-9.52 years), the composite endpoint (sustained ventricular tachycardia, aborted SCD, implantable cardioverter-defibrillator therapy, SCD, HFd, and HTx) was achieved in 15 additional patients with HFd/HTx (n = 5) and SCD/aborted SCD/implantable cardioverter-defibrillator therapy/sustained ventricular tachycardia (n = 10). Male sex (P = 0.004), nonsustained ventricular tachycardia (P = 0.017) and LV ejection fraction ≤50% (P = 0.012) were associated with the composite endpoint. Males with DES variants had similar outcomes to historical FLNC-tv and LMNA-tv controls. However, females showed better outcomes than those with LMNA-tv. In vitro experiments showed the characteristic finding of DES aggregates in 7 of 12 variants., Conclusions: DES ACM is associated with poor outcomes which can be predicted with potentially successful treatments, underscoring the importance of familial evaluation and genetic studies to identify at risk individuals., Competing Interests: Funding Support and Author Disclosures Dr Bermudez-Jimenez has received grants from Instituto de Salud Carlos III (ISCIII) through the project JR21/00031 (cofounded by European Regional Development Fund). Dr Zorio has received grants from the Instituto de Salud Carlos III through the projects PI18/01582 and PI21/01282 (co-funded by European Regional Development Fund “A way to make Europe”). Dr Brodehl has received grants from the Medical Faculty of the Ruhr-University Bochum (FoRUM, F1074-2023) and the ‘Deutsche Herzstiftung e.V. (Frankfurt a.M., Germany); and is a shareholder with Tenaya Therapeutics. Dr Lopes has received grants from a Medical Research Council (MRC) Clinical Academic Research Partnership (CARP) award (MR/T005181/1). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: The purpose of this review is to provide an overview of recent evidence on female-specific risk factors related to reproductive status or pregnancy., Recent Findings: Pregnancy-related factors, including hypertensive disorders and gestational diabetes, increase the risk of heart failure in women, while breastfeeding and hormone therapy may offer protection. Hypertensive disorders of pregnancy, gestational diabetes, polycystic ovarian syndrome, placental abruption, younger maternal age at first live birth, younger maternal age at last live birth, number of stillbirths, number of pregnancies, onset of menstruation before 12 years of age, shorter reproductive age, ovariectomy, and prolonged absence of ovarian hormones may increase the risk of heart failure in women. Conversely, breastfeeding status and hormone therapy (for menopause or contraception) may serve as protective factors, while fertility treatments have no discernible effect on the risk of heart failure., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Atrial fibrillation (AF) is a frequent cardiovascular (CV) comorbidity in cancer., Objectives: The purpose of this study was to examine clinical characteristics and contemporary management of patients with AF and cancer with a specific focus on antithrombotic treatments., Methods: This was a prospective, multicenter, observational study of patients with a recent cancer diagnosis and electrocardiographically confirmed AF (the BLITZ-AF Cancer Registry). CHA 2 DS 2 VASc scores were calculated for study participants., Results: Overall, 1,514 individuals were enrolled from June 2019 to September 2021 (mean age 74 ± 9 years, 47.5% of participants >75 years of age; 63.5% males). CV diseases were common: 20.9% had heart failure, 18.1% had coronary artery disease, 38.5% had valvular heart disease, and 9.8% had peripheral artery disease. Previous thromboembolic and hemorrhagic events occurred in 13.9% and 10.4% of subjects, respectively. The most common cancer types were lung (14.9%), colorectal (14.1%), prostate (8.8%), and non-Hodgkin lymphoma (8.1%). In total, 41.5% of the patients had a CHA 2 DS 2 VASc score ≥4. Before admission or prior to cardiologist consultation, 16.6% of subjects were not taking any antithrombotic therapy and 22.7% were receiving antiplatelet agents and/or low-molecular-weight heparin. At discharge or after cardiologic assessment, these percentages dropped to 7.7% and 16.6%, respectively. This trend was paralleled by an increase in the use of direct-acting oral anticoagulant, while the proportion of vitamin K antagonist declined., Conclusions: This study demonstrates that there is underuse of appropriate antithrombotic therapy for AF in cancer patients highlighting the need to integrate early CV assessment in the management of these patients. (Non-interventional Study on Patients With Atrial Fibrillation and Cancer [BLITZ-AF Cancer]; NCT03909386)., Competing Interests: The study was realized by Heart Care Foundation with own research funds, partially supported by a not conditional grant by Daiichi Sankyo Italia. Dr Ameri received speaker and/or advisor fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Daiichi Sankyo, Janssen, and MSD, all outside the scope of this work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Purpose: To determine cardiovascular health (CVH) trajectories and their association with sociodemographic and cardiometabolic outcomes in adolescence., Methods: One thousand eighty adolescents attending 24 secondary schools enrolled in the SI! Program for Secondary Schools trial in Spain were assessed at approximately 12, 14, and 16 years of age. CVH was assessed according to American Heart Association criteria based on seven metrics (smoking status, body mass index, physical activity, diet, blood pressure, total cholesterol, and blood glucose), and CVH trajectories were identified by latent class trajectory modeling. Associations between CVH trajectories, sociodemographic characteristics, and cardiometabolic outcomes were analyzed using generalized linear and Poisson models., Results: Five CVH trajectory groups were identified: poor-stable (27 adolescents [2.5%]), intermediate-substantial rise (79 [7.3%]), intermediate-substantial decline (63 [5.8%]), intermediate-mild decline (403 [37.3%]), and intermediate-mild rise (508 [47.1%]). Boys and adolescents from families with low-average income, low-intermediate educational attainment, and a migrant background more frequently belonged to groups with lower baseline CVH and poor or declining trajectories. The intermediate-substantial decline group had the highest prevalence ratio for overweight/obesity (3.84; 95% confidence interval: 2.86-5.16) and metabolic syndrome (4.93; 95% confidence interval: 1.21-20.04) at age 16, whereas prevalence was lowest in the intermediate-mild rise group., Discussion: Adolescent CVH trajectories differ according to socioeconomic characteristics and are associated with cardiometabolic outcomes. Primordial prevention interventions should be implemented early in life, taking into account CVH trajectories and with a particular focus on vulnerable populations., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

A novel rare mutation in the pore region of Nav1.5 channels (p.L889V) has been found in three unrelated Spanish families that produces quite diverse phenotypic manifestations (Brugada syndrome, conduction disease, dilated cardiomyopathy, sinus node dysfunction, etc.) with variable penetrance among families. We clinically characterized the carriers and recorded the Na + current (I Na ) generated by p.L889V and native (WT) Nav1.5 channels, alone or in combination, to obtain further insight into the genotypic-phenotypic relationships in patients carrying SCN5A mutations and in the molecular determinants of the Nav1.5 channel function. The variant produced a strong dominant negative effect (DNE) since the peak I Na generated by p.L889V channels expressed in Chinese hamster ovary cells, either alone (-69.4 ± 9.0 pA/pF) or in combination with WT (-62.2 ± 14.6 pA/pF), was significantly (n ≥ 17, p < 0.05) reduced compared to that generated by WT channels alone (-199.1 ± 44.1 pA/pF). The mutation shifted the voltage dependence of channel activation and inactivation to depolarized potentials, did not modify the density of the late component of I Na , slightly decreased the peak window current, accelerated the recovery from fast and slow inactivation, and slowed the induction kinetics of slow inactivation, decreasing the fraction of channels entering this inactivated state. The membrane expression of p.L889V channels was low, and in silico molecular experiments demonstrated profound alterations in the disposition of the pore region of the mutated channels. Despite the mutation producing a marked DNE and reduction in the I Na and being located in a critical domain of the channel, its penetrance and expressivity are quite variable among the carriers. Our results reinforce the argument that the incomplete penetrance and phenotypic variability of SCN5A loss-of-function mutations are the result of a combination of multiple factors, making it difficult to predict their expressivity in the carriers despite the combination of clinical, genetic, and functional studies., Competing Interests: The authors declare no conflicts of interest.

The role of extracellular nucleotides as modulators of inflammation and cell stress is well established. One of the main actions of these molecules is mediated by the activation of purinergic receptors (P2) of the plasma membrane. P2 receptors can be classified according to two different structural families: P2X ionotropic ion channel receptors, and P2Y metabotropic G protein-coupled receptors. During inflammation, damaged cells release nucleotides and purinergic signaling occurs along the temporal pattern of the synthesis of pro-inflammatory and pro-resolving mediators by myeloid and lymphoid cells. In macrophages under pro-inflammatory conditions, the expression and activity of cyclooxygenase 2 significantly increases and enhances the circulating levels of prostaglandin E 2 (PGE 2 ), which exerts its effects both through specific plasma membrane receptors (EP1-EP4) and by activation of intracellular targets. Here we review the mechanisms involved in the crosstalk between PGE 2 and P2Y receptors on macrophages, which is dependent on several isoforms of protein kinase C and protein kinase D1. Due to this crosstalk, a P2Y-dependent increase in calcium is blunted by PGE 2 whereas, under these conditions, macrophages exhibit reduced migratory capacity along with enhanced phagocytosis, which contributes to the modulation of the inflammatory response and tissue repair., (© 2023. The Author(s).)

Background: Less than 40% of patients with dilated cardiomyopathy (DCM) have a pathogenic/likely pathogenic genetic variant identified. TBX20 has been linked to congenital heart defects; although an association with left ventricular noncompaction (LVNC) and DCM has been proposed, it is still considered a gene with limited evidence for these phenotypes. This study sought to investigate the association between the TBX20 truncating variant ( TBX20tv ) and DCM/LVNC., Methods: TBX20 was sequenced by next-generation sequencing in 7463 unrelated probands with a diagnosis of DCM or LVNC, 22 773 probands of an internal comparison group (hypertrophic cardiomyopathy, channelopathies, or aortic diseases), and 124 098 external controls (individuals from the gnomAD database). Enrichment of TBX20tv in DCM/LVNC was calculated, cosegregation was determined in selected families, and clinical characteristics and outcomes were analyzed in carriers., Results: TBX20tv was enriched in DCM/LVNC (24/7463; 0.32%) compared with internal (1/22 773; 0.004%) and external comparison groups (4/124 098; 0.003%), with odds ratios of 73.23 (95% CI, 9.90-541.45; P <0.0001) and 99.76 (95% CI, 34.60-287.62; P <0.0001), respectively. TBX20tv was cosegregated with DCM/LVNC phenotype in 21 families for a combined logarythm of the odds score of 4.53 (strong linkage). Among 57 individuals with TBX20tv (49.1% men; mean age, 35.9±20.8 years), 41 (71.9%) exhibited DCM/LVNC, of whom 14 (34.1%) had also congenital heart defects. After a median follow-up of 6.9 (95% CI, 25-75:3.6-14.5) years, 9.7% of patients with DCM/LVNC had end-stage heart failure events and 4.8% experienced malignant ventricular arrhythmias., Conclusions: TBX20tv is associated with DCM/LVNC; congenital heart defect is also present in around one-third of cases. TBX20tv -associated DCM/LVNC is characterized by a nonaggressive phenotype, with a low incidence of major cardiovascular events. TBX20 should be considered a definitive gene for DCM and LVNC and routinely included in genetic testing panels for these phenotypes., Competing Interests: Disclosures Drs Amor-Salamanca, de la Higuera Romero, Cárdenas-Reyes, García-Hernández, Valverde-Gómez, Gómez-Díaz, and Ochoa are employees of Health in Code SL. The other authors report no conflicts.

The small GTPase RhoA and the downstream Rho kinase (ROCK) regulate several cell functions and pathological processes in the vascular system that contribute to the age-dependent risk of cardiovascular disease, including endothelial dysfunction, excessive permeability, inflammation, impaired angiogenesis, abnormal vasoconstriction, decreased nitric oxide production and apoptosis. Frailty is a loss of physiological reserve and adaptive capacity with advanced age and is accompanied by a pro-inflammatory and pro-oxidative state that promotes vascular dysfunction and thrombosis. This review summarises the role of the RhoA/Rho kinase signalling pathway in endothelial dysfunction, the acquisition of the pro-thrombotic state and vascular ageing. We also discuss the possible role of RhoA/Rho kinase signalling as a promising therapeutic target for the prevention and treatment of age-related cardiovascular disease., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Contrast-Induced Acute Kidney Injury (CI-AKI) remains a frequent iatrogenic condition since radiological procedures using intra-vascular iodinated contrast media (CM) are being widely administered for diagnostic and therapeutic purposes. Despite the improvement of the medical healthcare system worldwide, CI-AKI is still associated with direct short-term and indirect long-term outcomes including increased morbidity and mortality, especially in patients with underlying pre-existing renal function impairment, cardiovascular disease, or diabetes that could rapidly progress into Chronic Kidney Disease. Although the RIFLE (Risk, Injury, Failure, Loss, End-Stage Kidney Disease), AKIN (Acute Kidney Injury Network), and KDIGO (Kidney Disease Improving Global Outcomes) clinical criteria and recommendation guidelines are based on traditional "gold standard" biomarkers known as serum creatinine, glomerular filtration rate, and urinary output, new reliable serum and urinary biomarkers are still needed for an effective unified diagnostic strategy for AKI. Starting from previous and recent publications on the benefits and limitations of validated biomarkers responding to kidney injury, glomerular filtration, and inflammation among others, this review unravels the role of new emerging biomarkers used alone or in combination as reliable tools for early diagnosis and prognosis of CI-AKI, taking into account patients and procedures-risk factors towards a new clinical perspective.

Aims: The present analysis from the Functional Assessment in Elderly Myocardial Infarction Patients with Multivessel Disease (FIRE) trial aims to explore the significance of pre-admission physical activity and assess whether the benefits of physiology-guided complete revascularization apply consistently to sedentary and active older patients., Methods and Results: Patients aged 75 years or more with myocardial infarction (MI) and multivessel disease were randomized to receive physiology-guided complete revascularization or culprit-only strategy. The primary outcome was a composite of death, MI, stroke, or any revascularization within a year. Secondary endpoints included the composite of cardiovascular death or MI, as well as single components of the primary endpoint. Pre-admission physical activity was categorized into three groups: (i) absent (sedentary), (ii) light, and (iii) vigorous. Among 1445 patients, 692 (48%) were sedentary, whereas 560 (39%) and 193 (13%) performed light and vigorous physical activity, respectively. Patients engaging in light or vigorous pre-admission physical activity exhibited a reduced risk of the primary outcome compared with sedentary individuals [light hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.55-0.91 and vigorous HR 0.14, 95% CI 0.07-0.91, respectively]. These trends were also observed for death, cardiovascular death, or MI. When comparing physiology-guided complete revascularization vs. culprit-only strategy, no significant interaction was observed for primary and secondary endpoints when stratified by sedentary or active status., Conclusion: In older patients with MI, pre-admission physical activity emerges as a robust and independent prognostic determinant. Physiology-guided complete revascularization stands out an effective strategy in reducing ischaemic adverse events, irrespective of pre-admission physical activity status., Clinical Trial Registration: ClinicalTrials.gov NCT03772743., Competing Interests: Conflict of interest: G.Cam. received research grants and personal fees from ABBOTT VASCULAR, personal fees from MENARINI, personal fees from AMGEN, personal fees from SANOFI, outside the submitted work. S.B. received personal fees from ABBOTT VASCULAR, outside the submitted work., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Cardiac device infections are serious adverse events associated with considerable morbidity and mortality, significant costs, and increased healthcare utilization. The aim of this study is to calculate the costs of treatment of cardiac implantable electrostimulation device (CIED)-related infections for different types of infection (local or systemic) and therapeutic approaches. Patients and Methods : Single-center cohort (1985-2018). The costs of the CIED-related infections were analyzed according to initial treatment (antimicrobial treatment exclusively, local approach, or transvenous lead extraction (TLE)). Total costs (including those for hospitalization stay, drugs, extraction material, and newly implanted devices) were assigned to each case until its final resolution. Results : A total of 380 cases (233 local and 147 systemic infections) were analyzed. The average cost of systemic infection was EUR 34,086, mainly due to hospitalization (78.5%; mean: 24 ± 14 days), with a mortality rate of 10.8%. Local infection had a mortality rate of 2.5% (mainly related to the extraction procedure) and an average cost of EUR 21,790, which was higher in patients with resynchronization therapy devices and defibrillators (46% of total costs). Surgical procedures limited to the pocket for local infections resulted in a high rate of recurrence (87%), evolved to systemic infections in 48 patients, and had a higher cost compared to TLE (EUR 42,978 vs. EUR 24,699; p < 0.01). Conclusions : The costs of treating CIED-related infections are high and mainly related to the type of treatment and length of hospitalization. Complete device removal is always the most effective approach and is a cost-saving strategy.

Background: There is scarce evidence supporting the clinical utility of congestive intrarenal venous flow (IRVF) patterns in patients with acute heart failure., Objectives: This study aims to: 1) investigate the association between IRVF patterns and the odds of worsening renal function (WRF); 2) track the longitudinal changes of serum creatinine (sCr) across IRVF at predetermined points and its association with decongestion; and 3) explore the relationship between IRVF/WRF categories and patient outcomes., Methods: IRVF was assessed at baseline (pre-decongestive therapy), 72 hours, and 30 and 90 days postdischarge. Changes in sCr trajectories across dynamic IRVF variations and parameters of decongestion were assessed using linear mixed effect models. The association between IRVF/WRF categories and outcomes was evaluated using univariable/multivariable models., Results: In this prospective, multicenter study with 188 participants, discontinuous IRVF patterns indicated higher odds of WRF (OR: 3.90 [95% CI: 1.24-12.20]; P = 0.020 at 72 hours; and OR: 5.76 [95% CI: 1.67-19.86]; P = 0.006 at 30 days) and an increase in sCr (Δ-72 hours 0.14 mg/dL [95% CI: 0.06-0.22]; P = 0.001; Δ-discharge 0.13 mg/dL [95% CI: 0.03-0.23]; P = 0.007). However, the diuretic response and decongestion significantly influenced the magnitude of these changes. Patients exhibiting both WRF and discontinuous IRVF at 30 days experienced an increased hazard of adverse events (HR: 5.96 [95% CI: 2.63-13.52]; P < 0.001)., Conclusions: Discontinuous IRVF identifies patients with higher odds of WRF during admission and postdischarge periods. Nonetheless, adequate diuretic response and decongestion could modify this association. Patients showing both WRF and discontinuous IRVF at 30 days had increased rates of adverse events., Competing Interests: Funding Support and Author Disclosures This work was supported by grants from the Ministry of Economy and Competitiveness, Instituto Carlos III (PI20/00392), CIBER Cardiovascular (16/11/00420 and 16/11/00403), and Heart Failure Association of the Spanish Society of Cardiology (2019). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: We conducted a study to determine the prevalence of structural heart disease in patients with CF, the characteristics of a cardiomyopathy not previously described in this population, and its possible relationship with nutritional deficiencies in CF., Methods: We studied 3 CMP CF patients referred for heart-lung transplantation and a prospective series of 120 adult CF patients. All patients underwent a clinical examination, blood tests including levels of vitamins and trace elements, and echocardiography with evaluation of myocardial strain. Cardiac magnetic resonance imaging (CMR) was performed in patients with CMP and in a control group. Histopathological study was performed on hearts obtained in transplant or necropsy., Results: We found a prevalence of 10% (CI 4.6%-15.4%) of left ventricular (LV) dysfunction in the prospective cohort. Myocardial strain parameters were already altered in CF patients with otherwise normal hearts. Histopathological examination of 4 hearts from CF CMP patients showed a unique histological pattern of multifocal myocardial fibrosis similar to Keshan disease. Four of the five CF CMP patients undergoing CMR showed late gadolinium uptake, with a characteristic patchy pattern in 3 cases ( p  < 0.001 vs. CF controls). Selenium deficiency (Se < 60 µg/L) was associated with more severe LV dysfunction, higher prevalence of CF CMP, higher NTproBNP levels, and more severe pulmonary and digestive involvement., Conclusion: 10% of adults with CF showed significant cardiac involvement, with histological and imaging features resembling Keshan disease. Selenium deficiency was associated with the presence and severity of LV dysfunction in these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Segovia-Cubero, Ruiz-Bautista, Maiz-Carro, Girón-Moreno, Prados-Sánchez, Martínez-Martínez, González-Estecha, Mingo-Santos, Gómez-Bueno, Salas-Antón, Cavero-Gibanel, Pastrana-Ledesma, García-Pavía, Laporta-Hernández, Sánchez-Ortiz and Alonso-Pulpón.)

Nucleotide-binding oligomerization domain-like (NOD) receptors rely on the interface between immunity and metabolism. Dietary factors constitute critical players in the activation of innate immunity and modulation of the gut microbiota. The latter have been involved in worsening or improving the control and promotion of diseases such as obesity, type 2 diabetes, metabolic syndrome, diseases known as non-communicable metabolic diseases (NCDs), and the risk of developing cancer. Intracellular NODs play key coordinated actions with innate immune 'Toll-like' receptors leading to a diverse array of gene expressions that initiate inflammatory and immune responses. There has been an improvement in the understanding of the molecular and genetic implications of these receptors in, among others, such aspects as resting energy expenditure, insulin resistance, and cell proliferation. Genetic factors and polymorphisms of the receptors are determinants of the risk and severity of NCDs and cancer, and it is conceivable that dietary factors may have significant differential consequences depending on them. Host factors are difficult to influence, while environmental factors are predominant and approachable with a preventive and/or therapeutic intention in obesity, T2D, and cancer. However, beyond the recognition of the activation of NODs by peptidoglycan as its prototypical agonist, the underlying molecular response(s) and its consequences on these diseases remain ill-defined. Metabolic (re)programming is a hallmark of NCDs and cancer in which nutritional strategies might play a key role in preventing the unprecedented expansion of these diseases. A better understanding of the participation and effects of immunonutritional dietary ingredients can boost integrative knowledge fostering interdisciplinary science between nutritional precision and personalized medicine against cancer. This review summarizes the current evidence concerning the relationship(s) and consequences of NODs on immune and metabolic health.

Introduction: This study aimed to evaluate the association between the NephroCheck® test AKIRisk® score, diuretic efficiency (DE), and the odds of worsening kidney function (WKF) within the first 72 h of admission in patients hospitalized for acute heart failure (AHF)., Methods: The study prospectively enrolled 125 patients admitted with AHF. NephroCheck® test was obtained within the first 24 h of admission. DE was defined as net fluid urine output per 40 mg of furosemide equivalents., Results: The median AKIRisk® score was 0.11 (IQR 0.06-0.34), and 38 (30.4%) patients had an AKIRisk® score &gt;0.3. The median cumulative DE at 72 h was 1,963 mL (IQR 1317-3,239 mL). At 72 h, a total of 10 (8%) patients developed an absolute increase in sCr ≥0.5 mg/dL (WKF). In a multivariable setting, there was an inverse association between the AKIRisk® score and DE within the first 72 h. In fact, the highest the AKIRisk® score (centered at 0.3), the higher the likelihood of poor DE (below the median) and WKF at 72 h (odds ratio [OR] 2.04; 95%; CI: 1.02-4.07; p = 0.043, and OR 3.31, 95% CI: 1.30-8.43; p = 0.012, respectively)., Conclusion: In patients with AHF, a higher NephroCheck® AKIRisk® score is associated with poorer DE and a higher risk of WKF at 72 h. Further research is needed to confirm the role of urinary cell cycle arrest biomarkers in the AHF scenario., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: The use of urinary sodium to guide diuretics in acute heart failure is recommended by experts and the most recent European Society of Cardiology guidelines. However, there are limited data to support this recommendation. The ENACT-HF study (Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure) investigated the feasibility and efficacy of a standardized natriuresis-guided diuretic protocol in patients with acute heart failure and signs of volume overload., Methods: ENACT-HF was an international, multicenter, open-label, pragmatic, 2-phase study, comparing the current standard of care of each center with a standardized diuretic protocol, including urinary sodium to guide therapy. The primary end point was natriuresis after 1 day. Secondary end points included cumulative natriuresis and diuresis after 2 days of treatment, length of stay, and in-hospital mortality. All end points were adjusted for baseline differences between both treatment arms., Results: Four hundred one patients from 29 centers in 18 countries worldwide were included in the study. The natriuresis after 1 day was significantly higher in the protocol arm compared with the standard of care arm (282 versus 174 mmol; adjusted mean ratio, 1.64; P <0.001). After 2 days, the natriuresis remained higher in the protocol arm (538 versus 365 mmol; adjusted mean ratio, 1.52; P <0.001), with a significantly higher diuresis (5776 versus 4381 mL; adjusted mean ratio, 1.33; P <0.001). The protocol arm had a shorter length of stay (5.8 versus 7.0 days; adjusted mean ratio, 0.87; P =0.036). In-hospital mortality was low and did not significantly differ between the 2 arms (1.4% versus 2.0%; P =0.852)., Conclusions: A standardized natriuresis-guided diuretic protocol to guide decongestion in acute heart failure was feasible, safe, and resulted in higher natriuresis and diuresis, as well as a shorter length of stay., Competing Interests: Disclosures Dr Dauw received speaker fees from AstraZeneca, Boehringer-Ingelheim, and Bayer; Dr Lelonek received speaker and consulting fees from Novartis, Novo Nordisk, Servier, AstraZeneca, Boehringer-Ingelheim, Bausch Health, Bayer, Ewopharma, and Gedeon Richter and was involved in clinical trials from Amgen, Novartis, Novo Nordisk, and Boehringer-Ingelheim; Dr Borbély received speaker fees from Astra Zeneca, Bayer, Boehringer-Ingelheim, and Novartis; Dr Cobo-Marcos received speaker fees from Astra Zeneca, Boehringer-Ingelheim, Novartis, Vifor Pharma, Novo Nordisk, and Bayer; Dr Barge-Caballero received travel grants and speaker fees from Astra Zeneca, Boehringer-Ingelheim, Novartis, Viatris, and Pfizer and received research grants from Pfizer; Dr Barker received speaker fees from AstraZeneca, Novartis, and Medtronic; Dr Doghmi received speaker fees from Novartis, Boehringer-Ingelheim, and Pfizer; Dr Nijst received speaker fees from Novartis, Boehringer-Ingelheim, and Bayer; and Dr Martens received consultancy fees from Novartis and CLS Vifor and is supported by a research grant from the Belgian American Educational Foundation and the Frans Van de Werf Fund. The other authors report no conflicts.

Introduction and Objectives: Patients with combined heart failure (HF) and chronic kidney disease (CKD) have been underrepresented in clinical trials. The prevalence of CKD in these patients and their clinical profile require constant evaluation. This study aimed to analyze the prevalence of CKD, its clinical profile, and patterns of use of evidence-based medical therapies in HF across CKD stages in a contemporary cohort of ambulatory patients with HF., Methods: From October 2021 to February 2022, the CARDIOREN registry included 1107 ambulatory HF patients from 13 HF clinics in Spain., Results: The median age was 75 years, 63% were male, and 48% had heart failure with reduced left ventricular ejection fraction (HFrEF). A total of 654 (59.1%) had an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 , and 122 (11%) patients with eGFR ≥ 60 mL/min/1.73 m 2 had a urine albumin-creatinin ratio ≥ 30 mg/g. The most important variables associated with lower eGFR were age (R2=61%) and furosemide dose (R2=21%). The proportion of patients receiving an angiotensin-converting enzyme inhibitor (ACEI)/ angiotensin II receptor blockers (ARB), an angiotensin receptor-neprilysin inhibitor (ARNi), a sodium-glucose cotransporter 2 inhibitor (SGLT2i), or a mineralocorticoid receptor antagonist (MRA) progressively decreased with lower eGFR categories. Notably, 32% of the patients with HFrEF and an eGFR <30 mL/min/1.73 m 2 received the combination of ACEI/ARB/ARNi+beta-blockers+MRA+SGLT2i., Conclusions: In this contemporary HF registry, 70% of patients had kidney disease. Although this population is less likely to receive evidence-based therapies, structured and specialized follow-up approaches within HF clinics may facilitate the adoption of these life-saving drugs., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)