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There is a clear need for a non-invasive biomarker that could allow surveillance of acute cellular rejection (ACR) without the need of repeated endomyocardial biopsies (EMB) in heart transplant (HT) recipients. Donor-derived cell-free DNA (dd-cfDNA) is currently under study for this purpose. This was a multicenter, observational, prospective study. According to protocol, all patients included underwent surveillance EMB at 15 days, 1, 2, 3, 4, 6 and 12 months post-HT. Dd-cfDNA levels were determined prior to each EMB, using Next Generation Sequencing technology (Allonext® assay, Eurofins Genome). Primary end-point was the association between dd-cfDNA levels and the presence of ACR, as determined by ISHLT 2004 classification. We herein report the results of the first 848 pairs of EMB-dd-cfDNA determinations. The cohort included 206 recipients from 12 different centers (mean age 54 ± 11 years, 73% male). ACR, defined as grade ≥2R, was present in 35 EMB (4.1%), and AMR ≥1 in 14 EMB (1.7%). Median dd-cfDNA values for each ACR group were: 0R 0.088% (0.038-0.22), 1R 0.15% (0.056-0.4), 2R 0.23% (0.06-0.6) and 3R 0.6%. AMR0 median (IQR) values were 0.1% (0.04-0.24), and AMR≥1, 0.2% (0.075-0.7), respectively. In order to reduce the skewness, %ddcfDNA was logtransformed as log2(x+0.01) (Figure 1A). Using a GEE (generalized estimating equation) model, we found a statistically significant association between %dd-cfDNA and ACR ≥2R (OR 1.23, IQR 1.04-1.45), p <0.01 (Figure 1B). A 0.15% ddcf-DNA threshold revealed a negative predictive value of 97%, and could allow to save 57% of surveillance EMB. Dd-cfDNA appears to be an excellent biomarker for acute cellular rejection. Its high negative predictive value could allow to eliminate the need to perform a significant percentage of surveillance EMB currently performed in HT recipients. [ABSTRACT FROM AUTHOR]

Donor-derived cell-free DNA (dd-cfDNA) has shown a good ability to rule out acute cellular rejection (ACR) in heart transplant (HT) recipients, and is thus a promising biomarker for this entity. NTproBNP is a widely available biomarker, but there is scarce information on its relation with ACR, and its possible correlation with dd-cfDNA in this setting. We prospectively obtained levels of both biomarkers in all patients included in the FreeDNA-CAR study (NCT 04973943). According to protocol, all HT recipients underwent surveillance endomyocardial biopsies (EMB) at 15 days, 1, 2, 3, 4, 6 and 12 months post-HT, between April 2019 and April 2022. Biomarker levels were extracted prior to EMB. Primary end-point of this subanalysis was the correlation between dd-cfDNA and NTproBNP levels. The cohort included 206 HT patients from 12 different centers (mean age 54 ± 11 years, 73% male). We report the analysis of the first 848 visits. ACR, defined as grade ≥2R, was present in 35 EMB (4.1%), and AMR≥1 in 14 EMB (1.7%). Median (IQR) NTproBNP values for each ACR group were: 0R 1100 pg/ml (450-2580), 1R 1367 pg/ml (588-3298), 2R 2401 pg/ml (1115-6680) and 3R 4740 pg/ml (Figure 1A); and median dd-cfDNA values: 0R 0.088% (0.038-0.22), 1R 0.15% (0.056-0.4), 2R 0.23% (0.06-0.6) and 3R 0.6%. Using a GEE (generalized estimating equation) approach (Figure 1B), a statistically significant correlation between both biomarkers was found, with a coefficient of 0.002 ± 0.0006, meaning that for every increase of 100 units of NTproBNP, %dd-cfDNA increased in 0.002 (p < 0.001). In a cohort of HT patients in their first post-transplant year, dd-cfDNA and NT-proBNP showed a good correlation. Further studies are needed in order to determine if the combination of both biomarkers could improve individual performance and increase the number of EMB that could be safely eliminated. [ABSTRACT FROM AUTHOR]

Malignant progression in cancer requires populations of tumor-initiating cells (TICs) endowed with unlimited self renewal, survival under stress, and establishment of distant metastases. Additionally, the acquisition of invasive properties driven by epithelial-mesenchymal transition (EMT) is critical for the evolution of neoplastic cells into fully metastatic populations. Here, we characterize 2 human cellular models derived from prostate and bladder cancer cell lines to better understand the relationship between TIC and EMT programs in local invasiveness and distant metastasis. The model tumor subpopulations that expressed a strong epithelial gene program were enriched in highly metastatic TICs, while a second subpopulation with stable mesenchymal traits was impoverished in TICs. Constitutive overexpression of the transcription factor Snai1 in the epithelial/TIC-enriched populations engaged a mesenchymal gene program and suppressed their self renewal and metastatic phenotypes. Conversely, knockdown of EMT factors in the mesenchymal-like prostate cancer cell subpopulation caused a gain in epithelial features and properties of TICs. Both tumor cell subpopulations cooperated so that the nonmetastatic mesenchymal-like prostate cancer subpopulation enhanced the in vitro invasiveness of the metastatic epithelial subpopulation and, in vivo, promoted the escape of the latter from primary implantation sites and accelerated their metastatic colonization. Our models provide new insights into how dynamic interactions among epithelial, self-renewal, and mesenchymal gene programs determine the plasticity of epithelial TICs. [ABSTRACT FROM AUTHOR]

Background: The current incidence and outcomes of structural transcatheter procedures in heart transplant (HTx) recipients and left-ventricular assist devices (LVAD) carriers is unknown., Aims: To provide insights on structural transcatheter procedures performed across HTx and LVAD patients in Spain., Methods: Multicenter, ambispective, observational nationwide registry., Results: Until May/2023, 36 percutaneous structural interventions were performed (78% for HTx and 22% for LVAD) widely varying among centers (0%-1.4% and 0%-25%, respectively). Percutaneous mitral transcatheter edge-to-edge (TEER) was the most common (n = 12, 33.3%), followed by trancatheter aortic valve replacement (n = 11, 30.5%), and tricuspid procedures (n = 9, 25%). Mitral TEER resulted in mild residual mitral regurgitation in all but one case, mean gradient was <5 mmHg in 75% of them at 1-year, with no mortality and 8.3% re-admission rate. Tricuspid TEER resulted in 100% none/mild residual regurgitation with a 1-year mortality and readmission rates of 22% and 28.5%, respectively. Finally, trancatheter aortic valve replacement procedures (n = 8 in LVADs due to aortic regurgitation and n = 3 in HTx), were successful in all cases with one prosthesis degeneration leading to severe aortic regurgitation at 1-year, 18.2% mortality rate and no re-admissions. Globally, major bleeding rates were 7.9% and 12.5%, thromboembolic events 3.7% and 12.5%, readmissions 37% and 25%, and mortality 22% and 25%, in HTx and LVADs respectively. No death was related to the implanted transcatheter device., Conclusions: Most centers with HTx/LVAD programs perform structural percutaneous procedures but with very inconsistent incidence. They were associated with good safety and efficacy, but larger studies are required to provide formal recommendations., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background/objectives: The direct bridge to urgent heart transplant (HT) with venoarterial extracorporeal membrane oxygenation (VA-ECMO) support has been associated with high morbidity and mortality. The objective of this study is to analyze the morbidity and mortality of patients transplanted with VA-ECMO and compare the presumed differences between various eras over a 17-year timeline., Methods: This is a prospective, observational study on consecutive patients stabilized with VA-ECMO and transplanted with VA-ECMO from July 2007 to December 2023 at a reference center (98 patients). Objective variables were mortality and morbidity from renal failure, venous thromboembolic disease (VTD), primary graft dysfunction (PGD), the need for tracheostomy, severe myopathy, reoperation, post-transplant ECMO, vascular complications, and sepsis/infection., Results: The percentage of patients who reached transplantation without the need for mechanical ventilation has increased over the periods studied. No significant differences were found between the study periods in 30-day mortality ( p = 0.822), hospital discharge ( p = 0.972), one-year mortality ( p = 0.706), or five-year mortality ( p = 0.797). Survival rates in these periods were 84%, 75%, 64%, and 61%, respectively. Comorbidities were very frequent, with an average of 3.33 comorbidities per patient. The most frequent were vascular complications (58%), the need for post-transplant ECMO (57%), and myopathy (55%). The development of myopathy and the need for post-transplant ECMO were higher in recent periods ( p = 0.004 and p = 0.0001, respectively)., Conclusions: VA-ECMO support as a bridge to HT allows hospital discharge for 3 out of 4 transplanted patients. This survival rate has not changed over the years. The comorbidities associated with this device are frequent and significant.

Introduction and Objectives: Heart transplant (HT) represents a major physiological stress, resulting in elevated levels of analytical biomarkers. This study aimed to determine whether changes in biomarker levels after HT can identify patients with a poor prognosis., Methods: A prospective longitudinal noninterventional study was conducted in 149 consecutive patients undergoing HT from July 2017 to July 2023. Biomarkers were assessed before HT and at 6, 24, 48, 72, and 96hours after HT. The biomarkers analyzed were high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatinine, and lactic acid. The primary outcome was a composite of death and severe primary graft failure (PGF)., Results: NT-proBNP and troponin levels remained highly elevated throughout the period and stabilized from the first 24hours post-HT. Lactate levels stabilized after the first 24hours, and creatinine from the second day onward. Exitus occurred in 23 (15%) of the patients, and severe PGF in 26 (17%). All biomarkers were significantly associated with the incidence of the combined event (P <.0001). Receiver operating characteristic curve analysis at 24hours showed significant areas under the curve (P=.0001). The greatest discriminatory power was observed for the NT-proBNP curve. A value of 10 000 pg/mL had a sensitivity of 90% and specificity of 80%., Conclusions: A significant elevation of post-HT analytical biomarkers was associated with mortality and/or severe PGF. Among the biomarkers analyzed, NT-proBNP was the most accurate in classifying patients., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: In heart failure (HF), not all episodes of decompensation are alike. The study aimed to characterize the clinical groups of decompensation and perform a survival analysis., Methods: A retrospective study was conducted on patients consecutively admitted for HF from 2018 to 2023. Patients who died during admission were excluded (final number 1,668). Four clinical types of HF were defined: low cardiac output ( n :83), pulmonary congestion ( n :1,044), mixed congestion ( n :353), and systemic congestion ( n :188)., Results: The low output group showed a higher prevalence of reduced left ventricular ejection fraction (93%) and increased biventricular diameters ( p  < 0.01). The systemic congestion group exhibited a greater presence of tricuspid regurgitation with dilatation and right ventricular dysfunction ( p :0.0001), worse renal function, and higher uric acid and CA125 levels ( p :0.0001). Diuretics were more commonly used in the mixed and, especially, systemic congestion groups ( p :0.0001). The probability of overall survival at 5 years was 49%, with higher survival in pulmonary congestion and lower in systemic congestion ( p :0.002). Differences were also found in survival at 1 month and 1 year ( p :0.0001)., Conclusions: Mortality in acute HF is high. Four phenotypic profiles of decompensation differ clinically, with distinct characteristics and varying prognosis in the short, medium, and long term., 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 López-Vilella, Guerrero Cervera, Donoso Trenado, Martínez Dolz and Almenar Bonet.)

Lymphoproliferative diseases are a heterogeneous set of malignant clonal proliferations of lymphocytes. Despite well-established diagnostic criteria, the diagnosis remains difficult due to their variety in clinical presentation and immunophenotypic profile. Lymphoid T-cell disorders are less common than B-cell entities, and the lack of a clear immunophenotypic characteristic makes their identification hard. Flow cytometry turned out to be a useful tool in diagnosing T-cell disorders and to resolve complicated cases, especially if the number of analyzable neoplastic cells is small. We present a case of a 55-year-old man with simultaneous lymphoproliferative neoplastic T-cell clones, one αβ and the other γδ, identified and characterized by flow cytometry (FC), exploiting the variable expression intensity of specific markers. However, the patient's rapid decline made it impossible to define a differential diagnosis in order to confirm the identity of the γδ clone, which remains uncertain. This case is added to the few other cases already documented in the literature, characterized by the co-existence of T-large granular lymphocytic leukemia (T-LGLL)-αβ and T-LGLL-γδ/Hepatosplenic T-cell lymphoma (HSTCL). Our case underlines the key role of sensitive diagnostic tools in the assessment of potential relationship between the diagnosis, prognosis, and treatment in the two pathologies.

Aims: Patients with heart failure (HF) can exhibit kinesiophobia, an excessive, debilitating, and irrational fear of movement. This study aimed to enhance the understanding of kinesiophobia in patients with HF by analysing associations with the following variables: musculoskeletal pain, quality of life, quality of sleep, functional capacity, disability, frailty, sex, and age., Methods and Results: In this cross-sectional study, 107 participants were included, with ages ranging from 28 to 97 years (57% men, mean age 73.18 ± 12.68 years). Multiple regression analyses were performed with all variables, including polynomial regressions for variables with a non-linear relationship. Kinesiophobia was significantly correlated (P < 0.01) with musculoskeletal pain, quality of life, quality of sleep, functional capacity, disability, and being at risk of frailty, while age and sex were not statistically significant. Frailty disability and musculoskeletal pain intensity were variables linearly associated with kinesiophobia, while quality of sleep and disability had a non-linear relationship with kinesiophobia., Conclusion: Kinesiophobia needs to be evaluated and better understood in patients with HF to improve physical activity and exercise adherence. This study found that musculoskeletal pain intensity, quality of sleep, disability, and frailty risk have a significant association with kinesiophobia in patients with HF. Our results suggest multi-dimensional associations of kinesiophobia in patients with HF, which require further examination and understanding., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction and Objectives: Repetitive ambulatory doses of levosimendan are an option as a bridge to heart transplantation (HT), but evidence regarding the safety and efficacy of this treatment is scarce. The objective of the LEVO-T Registry is to describe the profile of patients on the HT list receiving levosimendan, prescription patterns, and clinical outcomes compared with patients not on levosimendan., Methods: We retrospectively reviewed all patients listed for elective HT from 2015 to 2020 from 14 centers in Spain., Results: A total of 1015 consecutive patients were included, of whom 238 patients (23.4%) received levosimendan. Patients treated with levosimendan had more heart failure (HF) admissions in the previous year and a worse clinical profile. The most frequent prescription pattern were fixed doses triggered by the patients' clinical needs. Nonfatal ventricular arrhythmias occurred in 2 patients (0.8%). No differences in HF hospitalizations were found between patients who started levosimendan in the first 30 days after listing and those who did not (33.6% vs 34.5%; P=.848). Among those who did not, 102 patients (32.9%) crossed over to levosimendan after an HF admission. These patients had a rate of 0.57 HF admissions per month before starting levosimendan and 0.21 afterwards. Propensity score matching analysis showed no differences in survival at 1 year after listing between patients receiving levosimendan and those who did not (HR, 1.03; 95%CI, 0.36-2.97; P=.958) or in survival after HT (HR, 0.97; 95%CI, 0.60-1.56; P=.958)., Conclusions: Repetitive levosimendan in an ambulatory setting as a bridge to heart transplantation is commonly used, is safe, and may reduce HF hospitalizations., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Aims: After heart transplantation (HTx), increments in physical activity (PA) are strongly recommended. However, participation rates in exercise-based cardiac rehabilitation and engagement in PA are insufficient in many patients. Hence, this study aimed to explore the central factors and the interconnections among distinct types of motivation to exercise, PA, sedentary time, psychosomatic, diet, and activity limitation characteristics in post-HTx patients., Methods and Results: This is a cross-sectional study involving 133 post-HTx patients (79 men, mean age 57 ± 13 years, mean time from transplantation 55 ± 42 months) recruited from an outpatient clinic in Spain. The patients were asked to fill in questionnaires measuring self-reported PA, motivation to exercise, kinesiophobia, musculoskeletal pain, quality of sleep, depression, functional capacity, frailty, sarcopenia risk, and diet quality. Two network structures were estimated: one network including PA and one network including sedentary time as nodes. The relative importance of each node in the network structures was determined using centrality analyses. According to the strength centrality index, functional capacity and identified regulation (subtypes of motivation to exercise) are the two most central nodes of the network (strength: z-score = 1.35-1.51). Strong and direct connections emerged between frailty and PA and between sarcopenia risk and sedentary time., Conclusion: Functional capacity and autonomous motivation to exercise are the most promising targets of interventions to improve PA levels and sedentary time in post-HTx patients. Furthermore, frailty and sarcopenia risk were found to mediate the effects of several other factors on PA and sedentary time., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. 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: Quadruple therapy (renin angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists and sodium/glucose cotransporter type 2 inhibitors [SGLT2i]) has become the current prognostic modifying treatment for heart failure (HF) with reduced ejection fraction (HFrEF). This study aimed to analyse the prescription´s evolution of this combination therapy, the analysis of each pharmacological group and the differences according to HF subgroups., Methods: Retrospective analysis of consecutive patients admitted for cardiac decompensation. Inclusion period: from 1-1-2020 to 12-31-2022. Patients with left ventricular ejection fraction > 40% and deceased during admission were excluded. Finally, 602 patients were included. These were divided into: (a) de novo HF without previous heart disease (n:108), (b) de novo with previous heart disease (n:107), and (c) non-de novo (n:387)., Results: Over the study time, all pharmacological groups experienced an increase in drugs prescription (p < 0.001). The group with the largest prescription rate increase was SGLT2i (2020:20%, 2021:42.9%, 2022:70.4%; mean increase 47.2%). The discharge rate prescription of quadruple therapy increased progressively (2020:7.4%, 2021:21.1%, 2022:32.5%; mean increase 21.9%). The subgroup with the highest combined prescription in 2022 was de novo with previous heart disease (43.9%)., Conclusion: The pharmacological group with the largest prescription´s rate increase was SGLT2i. The percentage of patients discharged on quadruple therapy has progressed significantly in recent years, although it remains low. The most optimised subgroup at discharge was that of de novo HF with previous heart disease., (© 2024. The Author(s).)

Background: Heart failure is frequently associated with kidney disease, and patients with kidney disease are at increased risk of heart failure. The co-occurrence of both entities not only significantly increases morbidity and mortality but also complicates therapy., Summary: Cardiorenal syndrome often requires a broad, comprehensive, and multidisciplinary approach. As a result, a need has arisen to create specialized cardiorenal units that allow for rigorous and personalized management of this condition. Moreover, in some cases, cardiorenal syndrome is more complex, owing to an acute and critical situation that requires the concept of the cardiorenal unit to be extended toward advanced diagnostic and therapeutic positions, thus confirming the need for an advanced cardiorenal unit. The creation of these units constitutes a real challenge, necessitating a specific multilevel action plan, covering governance and management, type of patient, personnel requirements, service portfolio, care process, information systems, and other resources. Specific lines of action must be proposed for each of the relevant points in order to facilitate development of these units, together with continuous evaluation of unit activity through specific indicators, and to detect areas for improvement., Key Messages: This study addresses the conditions and organizational characteristics that enable the creation, development, and continuous improvement of advanced cardiorenal units., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: The COVID-19 lockdown has been associated with reduced levels of physical activity, quality of life, and sleep quality, but limited evidence exists for its impact on heart failure patients. This study examined the influence of the COVID-19 lockdown on these aspects in heart failure patients, with specific comparisons by age and sex., Methods: A quasi-experimental cross-sectional study of patients with heart failure was conducted. The assessment involved two time points: during the COVID-19 lockdown (March to June 2020) and post-lockdown (July to October 2020). A total of 107 HF patients participated, with assessments of overall PA (using the International Physical Activity Questionnaire), QoL (employing the Cantril Ladder of Life), and sleep quality (utilizing the Minimal Insomnia Symptom Scale) conducted during and after the COVID-19 lockdown., Results: HF patients reported lower levels of total PA ( p = 0.001) and walking PA ( p < 0.0001) during lockdown than after lockdown, whilst no differences were observed in QoL nor sleep quality. In addition, both younger and older patients reported lower walking PA and total PA during lockdown than after lockdown, while older patients reported lower QoL during lockdown than after lockdown. Moreover, both men and women reported lower walking PA and total PA during lockdown than after lockdown, whilst women reported lower QoL., Conclusions: HF patients need improved PA programs during lockdowns, as these programs can elevate PA levels and enhance QoL, especially when faced with the risk of decompensation during health crises.

The impact of psychosocial stressors on cardiovascular health in women is of growing interest in both the popular and scientific literature. Rodent models are useful for providing direct experimental evidence of the adverse cardiovascular consequences of psychosocial stressors, yet studies in females are scarce. Here, we investigated the effects of repeated exposure to witness social defeat stress (WS) on cardiomyocyte contractile function and intracellular Ca 2+ homeostasis in young adult wild-type Groningen female rats. Female rats bore witness to an aggressive social defeat episode between two males for nine consecutive days or were exposed to a control procedure. Stress-related behaviors were assessed during the first and last WS/control exposure. Twenty-four hours after the last exposure, plasma corticosterone levels were measured, and cardiomyocytes were isolated for analyses of contractile properties and Ca 2+ transients, and expression levels of proteins involved in intracellular Ca 2+ dynamics. The results show an impairment of the intrinsic cardiac mechanical properties and prolonged intracellular Ca 2+ decay in WS female rats showing social stress-related behavioral (larger amounts of burying behavior) and neuroendocrine (elevated plasma corticosterone levels) phenotypes. Further, the results implicate alterations in the sarcoplasmic reticulum Ca 2+ -ATPase/phospholamban complex in the contractile defects described in cardiomyocytes of WS female rats. In conclusion, this study highlights the utility of the WS model as an ethologically relevant social stressor for investigating pathophysiological processes that occur in the heart of female subjects and may increase vulnerability to social stress-related cardiovascular risk., Competing Interests: Declaration of Competing Interest The authors state no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The cross-sectional study enrolled 231 patients with heart failure (n = 115; 60.87% were men; mean age, 74.34 ± 12.70 years) and heart transplantation (n = 116; 72.41% were men; mean age, 56.85 ± 11.87 years) who self-reported their technology usage, physical activity, and source of motivation for exercise. Patients with heart failure were significantly older ( P = .0001) than patients with heart transplantation. Physical activity levels in patients with heart failure decreased as the New York Heart Association classification increased. Patients with heart failure reported significantly lower physical activity than patients with heart transplantation ( P = .0008). Smartphones were the most widely used electronic device to access the Internet in both groups. Patients with heart transplantation seemed to use more than one device to access the Internet. In both groups, patients reporting more technology usage also reported higher levels of physical activity. Patients who accessed the Internet daily reported lower levels of physical activity. Whereas patients with heart failure identified encouragement by family members as a source of motivation for exercise, patients with heart transplantation reported that they were likely to exercise if motivated by their healthcare provider. Patients with heart failure and heart transplantation have unique technological and motivational needs that need consideration for mobile health-driven interventions., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The study aimed to study the influence of musculoskeletal pain on kinesiophobia in patients with heart failure. This cross-sectional study recruited 107 heart failure patients aged 73.18±12.68 years (57% men) from an outpatient setting. Participants self-reported pain using the Musculoskeletal System Assessment Inventory and the Cornell Musculoskeletal Discomfort Questionnaire. Kinesiophobia was assessed with the Tampa Scale for Kinesiophobia-11. About 62% reported musculoskeletal pain, with knees (16.8%) and lower back (12.%) being the most painful locations. About 31% reported moderate levels and 24% indicated high levels of kinesiophobia. There were positive and significant associations between the indicators of pain and kinesiophobia. Results showed an adequate structural equation model fit to the data with musculoskeletal pain factors explaining 22.09% of the variance in kinesiophobia. Assessment of kinesiophobia in patients with heart failure with musculoskeletal pain is essential to improve self-care and overall quality of life., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The treatment of congestion in heart failure (HF) is a challenge despite the therapeutic arsenal available. The aim of this study was to analyze different combinations of diuretics used to resolve congestion in patients admitted for decompensated HF and to define clinical profiles according to these treatments., Methods: Single-center study of 1,559 patients admitted for decompensated HF was done between 2016 and 2020. Patients were grouped according to the diuretic combination that led to clinical stabilization and discharge from the hospital: (1) Loop diuretic. (2) Loop diuretic + distal tubule (antialdosterone ± thiazides). (3) Loop diuretic + distal + proximal tubule (acetazolamide ± SGLT2 inhibitor). (4) Loop diuretic + distal tubule + collecting duct (tolvaptan). (5) Loop diuretic + distal + proximal + collecting duct. Based on these diuretic combinations, profiles with clinical, analytical, and echocardiographic differences were established., Results: There were more previous hospitalizations in groups 4 and 5 (p = 0.001) with a predominance of pulmonary congestion in profiles 1 and 2 and systemic congestion in 3, 4, and 5. Creatinine and CA125 were higher in profiles 4 and 5 (p = 0.01 and p = 0.0001), with no differences in NT-proBNP. Profiles 4 and 5 had a higher proportion of dilatation and depression of right ventricular (p = 0.0001) and left ventricular (p = 0.003) function. Diuretic therapy-defined groups showed difference in clinical characteristics., Conclusions: The diuretic treatment used identifies five clinical profiles according to the degree of congestion, renal function, CA125, and right ventricular functionality. These profiles would guide the best diuretic treatment on admission., (Copyright © 2023 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Introduction and Objective: In heart failure congestion is the most common symptom and diuretic resistance is frequent. This study aims to analyse whether short-term peripheral outpatient ultrafiltration (UF) is useful and safe in these patients., Material and Methods: The first 5 patients ultrafiltrated for diuretic resistance in a fast-track unit of a referral hospital for 12hours were analysed., Results: These patients were on treatment with at least 3 oral diuretics; UF made it possible to reduce and/or withdraw some of them. The volume extracted during the procedure was 1520±271ml. There were significant changes in diuresis (PreUF: 1360±164, PostUF: 1670±254ml; P=.035), weight (PreUF: 69.6±14, PostUF: 66.2±15kg; P=.0001) and creatinine (PreUF: 2.1±0.3, PostUF: 1.8±0.4mg; P= 0.023)., Conclusions: In outpatients with heart failure and diuretic resistance, short-course peripheral UF was effective and safe., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

Aims: Patients with heart failure (HF) admitted for decompensation often require high doses of intravenous diuretics. This study aims to analyse whether the use of peripheral ultrafiltration (UF) in patients hospitalized for acute HF with systemic-predominant congestion results in better hydric control, renal protection, and reduction of hospital stay compared with conventional treatment., Methods and Results: This study was a retrospective, comparative, single-centre study of 56 patients admitted for HF with systemic congestion with a poor diuretic response after diuretic escalation. One group underwent peripheral UF (35 patients) and others were maintained on intense diuretic treatment (control group, 21 patients). The diuretic response and days of hospital stay were compared between and within groups. The baseline characteristics of both groups were similar: males with right ventricular failure and renal dysfunction. The inter-group analysis showed that patients who received UF had better glomerular filtration rate (GFR; UF: 39.2 ± 18.2 vs. control: 28.7 ± 13.4 mL/min; P = 0.031) and higher diuresis (UF: 2184 ± 735 vs. control: 1335 ± 297 mL; P = 0.0001) at hospital discharge despite less need for diuretic drugs. Days of hospital stay were shorter in the UF group (UF: 11.7 ± 10.1 vs. control: 19.1 ± 14.4 days; P = 0.027). Intra-group analysis showed that patients receiving UF improved GFR, increased diuresis, and reduced weight at discharge (P < 0.001), whereas patients on conventional treatment only experienced improved weight but worsening renal function at discharge., Conclusions: In patients with acute HF with systemic congestion and diuretic resistance, UF compared with conventional treatment produces greater decongestion and renal protection, reduces the total diuretic load, and shortens the length of hospital stay., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

It is not clear to date whether a first admission in heart failure (HF) marks a worse evolution in patients not previously diagnosed with HF ("de novo HF") than those already diagnosed as outpatients ("acutely decompensated HF"). The aim of the study was to analyze whether survival in patients admitted for de novo HF differs from the survival in those admitted for a first episode of decompensation but with a previous diagnosis of HF. This study includes an analysis of 1,728 patients admitted for decompensated HF during 9 years. Readmissions and patients with left ventricular ejection fraction ≥50% were excluded (finally, 524 patients analyzed). We compared de novo HF (n = 186) in patients not diagnosed with HF, although their structural heart disease was defined, versus acutely decompensated HF (n = 338). The clinical profiles in both groups were similar. The de novo HF group more frequently presented with normal right ventricular function, with less presence of severe tricuspid regurgitation. The probability of survival was low in both groups. Thus, the median life in the de novo HF group was 2.1 years and in the acutely decompensated HF group, 3.5 years. There was a lower probability of long-term survival in the de novo HF group (p = 0.035). The variables associated with mortality were age (p <0.0001), ischemic heart disease (p <0.0001), hypertension (p = 0.009), obesity (p = 0.025), diabetes (p = 0.001), and N-terminal pro-brain natriuretic peptide at admission (p <0.0001). A higher glomerular filtration rate was associated with better survival (p = 0.033). De novo HF was associated with a higher mortality than chronic HF with acute decompensation (hazard ratio 1.53, 95% confidence interval 1.03 to 2.27, p = 0.036). In conclusion, the first admission for HF decompensation in patients with no previous diagnosis of HF identifies a subgroup of patients with higher long-term mortality., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: This study aims to analyse whether in acute heart failure (AHF) with iron deficiency (ID), the administration of ferric carboxymaltose (FCM) produces a greater benefit in renal dysfunction., Methods: A total of 812 consecutive patients admitted for AHF and ID were studied. Untreated (n:272) and treated (n:540) patients were compared. The six-month prevalence of a combined event (readmission for HF, all-cause death, and emergency department visit for decompensation) was analysed. Three grades of renal dysfunction (KDIGO) were compared, Group 1 (grades 1 and 2), Group 2 (grades 3a and 3b), and Group 3 (grades 4 and 5)., Results: There were differences in sex distribution (untreated group: males 39.7% vs. treated group: males 51.9%; p < 0.001). Sex-adjusted combined event analysis showed a greater benefit in Group 1 (OR: 0.31, 95% CI:0.19-0.5; p < 0.001) and Group 2 (OR: 0.23, 95% CI:0.14-0.38; p < 0.001), but not in Group 3 (OR: 0.51, 95% CI:0.17-0.55; p : 0.237)., Conclusions: The administration of FCM in patients with AHF and ID reduces the combined event analysed. The benefit is greater when renal dysfunction is present, except in very advanced degrees where no significant benefit is obtained.

Heart failure is a major problem in developed countries, leading to a high number of hospitalizations and healthcare costs. The most common symptom of heart failure is congestion, which is also the primary reason for hospitalization. Diuretics, particularly loop diuretics, are the cornerstone of the treatment of congestion. Likewise, there are other types of diuretics with different pathways of action, bioavailability profiles, adverse reactions, and effects on the cardiovascular and renal systems. Moreover, in recent years, new therapeutic alternatives have been proposed for challenging cases of diuretic resistance, such as ultrafiltration through peripheral access or peritoneal dialysis. The main objective of this article is to provide a step-guided approach to the management of congestion in patients with heart failure in order to guide the medical practice. Despite the significant amount of research published in recent years, there are no clear algorithms for managing acute heart failure. Diuretics remain the primary treatment of acute heart failure, and nephron blockade is key, but new therapies are emerging, and ongoing research is needed to develop better strategies for managing this condition., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The aim of this study was to explore the readiness for physical activity (PA) and its related factors in patients with heart failure. This cross-sectional study included 163 patients with heart failure (mean age 66 ± 16, 50% female). The ability to safely engage in PA was assessed with the PA Readiness Questionnaire (PAR-Q). Psychological readiness was measured using two questionnaires, namely: Exercise Self-efficacy Scale and the Motivation for PA and Exercise/Working Out. A multivariate analysis of covariance was conducted to test the effect of background variables on readiness for PA. 64% (n = 105) of patients reported not being able to safely engage in PA, 80% (n = 129) reported low self-efficacy, and 45% (n = 74) were extrinsically motivated indicating external factors drove their motivation. Factors that positively influenced the PA readiness included lower age (p < 0.01), being male (p < 0.01), being married (p < 0.01), having higher education (p < 0.01), being in NYHA-class I compared with II (p < 0.01), less time since diagnosis (p < 0.01), lower BMI (p = 0.02), and not suffering from COPD (p = 0.02). Prior to recommending exercise, assessment of safety to engage in PA along with self-efficacy and motivation in patients with heart failure is essential.

Background: This study aimed to compare well-being and physical activity (PA) before and during COVID-19 confinement in older adults with heart failure (HF), to compare well-being and PA during COVID-19 confinement in octogenarians and non-octogenarians, and to explore well-being, social support, attention to symptoms, and assistance needs during confinement in this population., Methods: A mixed-methods design was performed. Well-being (Cantril Ladder of Life) and PA (International Physical Activity Questionnaire) were assessed. Semi-structured interviews were performed to assess the rest of the variables., Results: 120 participants were evaluated (74.16 ± 12.90 years; octogenarians = 44.16%, non-octogenarians = 55.83%). Both groups showed lower well-being and performed less PA during confinement than before ( p < 0.001). Octogenarians reported lower well-being ( p = 0.02), higher sedentary time ( p = 0.03), and lower levels of moderate PA ( p = 0.04) during confinement. Most individuals in the sample considered their well-being to have decreased during confinement, 30% reported decreased social support, 50% increased their attention to symptoms, and 60% were not satisfied with the assistance received. Octogenarians were more severely impacted during confinement than non-octogenarians in terms of well-being, attention to symptoms, and assistance needs., Conclusions: Well-being and PA decreased during confinement, although octogenarians were more affected than non-octogenarians. Remote monitoring strategies are needed in elders with HF to control health outcomes in critical periods, especially in octogenarians.

Background. This study aims to determine whether the administration of ferric carboxymaltose (FCM) in patients with acute heart failure (AHF) and iron deficiency (ID) improves morbidity and mortality. Methods. We studied 890 consecutive patients admitted for AHF. Patients were divided into six groups according to reduced left ventricular ejection fraction (HFrEF) or preserved (HFpEF), presence of ID, and administration of FCM. Emergency visits, re-admissions, and all-cause mortality were assessed at 6 months. Results. The overall prevalence of ID was 91.2%. In the HFrEF group, no differences were found in isolated events when patients with untreated vs. treated ID were compared, while differences were found in the combined event rate (p = 0.049). The risk calculation showed an absolute risk reduction (ARR) of 10% and relative risk reduction (RRR) of 18%. In HFpEF there was a positive trend with regard to the combined event (p = 0.107), with an ARR of 9% and an RRR of 15%. The number of patients we needed to treat to prevent a combined event was 10.5 in HFrEF and 10.8 in HFpEF. Conclusions. FCM in AHF reduced the combined event rate of emergency visits, re-admission, and all-cause death at 6 months in HF with left ventricular ejection fraction <50%, and showed a positive trend in HFpEF.

Chronic social stress has been epidemiologically linked to increased risk for cardiovascular disease, yet the underlying pathophysiological mechanisms are still largely elusive. Mitochondrial (dys)function represents a potential intersection point between social stress exposure and (mal)adaptive cardiac responses. In this study, we used a rodent model of social stress to study the extent to which alterations in the cellular mechanical properties of the heart were associated with changes in indexes of mitochondrial function. Male adult rats were exposed to repeated episodes of social defeat stress or left undisturbed (controls). ECG signals were recorded during and after social defeat stress. Twenty-four hours after the last social defeat, cardiomyocytes were isolated for analyses of mechanical properties and intracellular Ca 2+ dynamics, mitochondrial respiration, and ATP content. Results indicated that social defeat stress induced potent cardiac sympathetic activation that lasted well beyond stress exposure. Moreover, cardiomyocytes of stressed rats showed poor contractile performance (e.g., slower contraction and relaxation rates) and intracellular Ca 2+ derangement (e.g., slower Ca 2+ clearing), which were associated with indexes of reduced reserve respiratory capacity and decreased ATP production. In conclusion, this study suggests that repeated social stress provokes impaired cardiomyocyte contractile performance and signs of altered mitochondrial bioenergetics in the rat heart. Future studies are needed to clarify the causal link between cardiac and mitochondrial functional remodeling under conditions of chronic social stress., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Published by Elsevier Ltd.)

Background: Currently, a high percentage of patients with congenital heart disease (CHD) reach adulthood. The consequence is that more and more patients will require a heart transplant (HTx) or heart-lung transplant (HLTx). The objective of the study was to analyze the evolution and temporary trend of the number of HTxs and HLTxs in patients with and without CHD., Methods: We performed a retrospective analysis of all HTxs and HTLxs from a Spanish transplant hospital. Retransplant and other combined transplants were excluded. HTx and HLTx were divided into 2 groups (CHD or non-CHD). The number of procedures of each modality was grouped in 5 years., Results: A total of 930 HTxs were analyzed between 1987 and 2020; 36 were CHD (18 HTxs and 18 HLTxs). HTx and HLTx in CHD showed a growing progressive trend, probably because of the greater number of these patients who reach adulthood and finally develop advanced heart failure. HTx in patients without CHD showed a very high rise in the first decade, reaching the maximum peak around the year 2000, with a poststabilization trend or even progressive reduction in the number of procedures. HLTx in patients without CHD showed a marked ascent during the first decade with a peak around 2005 and subsequent significant decline in recent years practically in disuse, probably because of the possibility of circulatory assistance in the case of right ventricular failure., Conclusions: The number of HTxs and HLTxs in CHD has a progressive rise. The number of HTx in patients without CHD remains relatively stable. HLTx in patients without CHD shows a marked decrease., (Copyright © 2022 Elsevier Inc. All rights reserved.)