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Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background Myocardial remodelling is a hallmark of heart failure (HF). Our previous proteomics analyses demonstrated a profound effect of beta blockers on cardiac extracellular matrix composition in ischaemic HF patients (1). No comprehensive proteomics characterizations has been performed in non-ischaemic HF patients. Methods Mass spectrometry was used to analyze intracellular and extracellular protein extracts from left ventricular samples obtained from patients with ischemic (n=65) and non-ischaemic (n=114) HF after heart transplantation, as well as non-failing controls (n=19). All HF patients had ventricular dilatation and reduced ejection fraction (EF%). Results The proteomics comparison across 198 cardiac samples with two tissue extracts revealed hallmarks of HF in both groups of patients compared to controls, including elevated levels of atrial natriuretric peptides and the fibroblast marker vimentin, as well as decreases in creatine kinase M/B, troponin C, and myosin light chain 2 (Figure 1). In comparison to ischaemic HF patients, non-ischaemic HF patients showed elevated levels of proteins involved in proteasome activation, consistent with the notion of increased protein degradation in cardiomyocytes even at the end stage of the disease (2). Despite similar clinical characteristics, myocardial remodelling in response to HF medications and the presence of comorbidities was different between the two HF groups. In ischaemic HF patients the use of β-blockers resulted in reduced proteoglycan deposition. In non-ischaemic patients, few protein changes were associated with medication. Instead, comorbidities such as atrial fibrillation and hypertension were critical determinants of myocardial protein remodelling in these HF patients (Figure 2). Notably, hypertensive HF patients showed a marked reduction in angiotensin converting enzyme 2 (ACE2) compared to normotensive patients, and this was accompanied by a reduction in Cysteine And Glycine Rich Protein 3 (CSRP3), a key player in the organization of cytosolic structures in cardiomyocytes, and the nuclear lamina proteins lamin A/C and B. The inflammation-related galectin 3-binding protein was reduced in hypertensive patients as were the extracellular proteases matrix metalloprotease 2, cathepsin G and chymase 1. Conclusion Our study constitutes the largest proteomics analysis of HF to date. We observed distinct protein remodelling processes in ischaemic and non-ischaemic HF patients and discerned the myocardial effects of medications and comorbidities such as hypertension. Open in new tab Download slide Ischaemic HF vs non-ischaemic HF. Open in new tab Download slide Effect of medications and comorbidities. [ABSTRACT FROM AUTHOR]

Background: There is a long-standing need for a non-invasive biomarker that allows monitoring of cardiac allograft rejection, avoiding the need for periodic endomyocardial biopsies (EMB)., Methods: Multicenter, observational, prospective study, performed between 2019 and 2023 (NCT04973943). All patients underwent 7 per-protocol surveillance EMB during the first post-HT year. Donor-derived cell-free DNA (dd-cfDNA) levels were determined before each EMB, using Next Generation Sequencing Technology (Allonext™ assay, Eurofins Genome). The primary endpoint was the association between dd-cfDNA levels and the presence of acute cellular rejection (ACR) in EMB., Results: The study included 206 patients from 12 centers, with 1090 pairs of EMB/dd-cfDNA determinations available for analysis. EMB with ACR (n=49) were associated to dd-cfDNA levels significantly higher than those without, median 0.189% (IQR 0.05-0.70) vs 0.095% (0.04-0.23), p=0.013. A dd-cfDNA threshold of 0.10% showed a negative predictive value for ACR of 97%. A statistically significant association between NTproBNP and dd-cfDNA was also found, with an increase of 0.007% dd-cfDNA (95%CI 0.003-0.011) for every 500 units of NTproBNP, p <0.001. The combination of both biomarkers for diagnosis of ACR showed an area under the ROC curve of 0.681, and this combined approach was significantly better than dd-cfDNA alone (area under the ROC curve 0.603), p = 0.016. Using a cut-off point of 0.10% for dd-cfDNA and 1000 UI/ml for NTproBNP, negative predictive value increased to 98.1%., Conclusions: Dd-cfDNA may be a useful biomarker to rule out significant ACR in a low-risk population. However, a dd-cfDNA value above normal threshold does not correlate robustly with the presence of disease. The combination with NTproBNP, a readily available biomarker, increased the discrimination power of dd-cfDNA alone., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Management of advanced heart failure (HF) remains challenging despite specific sections in the 2021 European Society of Cardiology/Heart Failure Association (ESC/HFA) guidelines, with delays in referrals exacerbating the issue. This study aimed to evaluate the awareness and implementation of these guidelines among cardiologists and identify barriers to effective referral., Methods and Results: From June to October 2023, an online survey was disseminated through the ESC mailing list, targeting cardiologists across Europe. The survey investigated four areas: guideline awareness, healthcare network organization, clinical case management, and perceptions of mechanical circulatory support (MCS) outcomes. Respondents were categorized into heart failure cardiologists (HFCs), general cardiologists (GCs), and other participants (OPs). Among 497 respondents, 25% were heart HFCs, 40% were GCs, and 35% were OPs. A total of 84% of HFCs reported a high level of guideline knowledge, compared to 57% of GCs and 62% of OPs (p < 0.001). Additionally, 76% of HFCs 'regularly or always' used ESC/HFA criteria to identify advanced HF, compared to 44% of GCs and 48% of OPs (p < 0.001). Correct responses regarding the recommendation class for heart transplantation were 84%, 55%, and 60% (p < 0.0001), and for MCS as a bridge to transplantation, 69%, 65%, and 55% (p = 0.018) among HFCs, GCs, and OPs, respectively. Referring patients with severe HF to a tertiary centre team was found to be 'very difficult' or 'difficult' by 8.4% of HFCs, 19.6% of GCs, and 18.2% of OPs (p = 0.0005)., Conclusion: The study highlights significant disparities in knowledge and application of advanced HF guidelines among cardiologists, revealing an opportunity for educational initiatives. The difficulty in referring patients to tertiary centres underscores the need to improve the referral pathway for advanced HF patients., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Left ventricular assist devices (LVADs) are an increasingly used strategy for the management of patients with advanced heart failure. Although these devices effectively improve survival, atrial and ventricular arrhythmias are common with a prevalence of 20-50% at one year after LVAD implantation. Arrhythmias predispose these patients to additional risk and are associated with considerable morbidity from recurrent implantable cardioverter-defibrillator shocks, progressive failure of the unsupported right ventricle, and herald an increased risk of mortality. Management of patients with arrhythmias and LVAD differs in many aspects from the general population heart failure patients. These include ruling out the reversible causes of arrhythmias that in LVAD patients may include mechanical irritation from the inflow cannula and suction events. For patients with symptomatic arrhythmias refractory to medical treatment, catheter ablation might be relevant. There are specific technical and procedural challenges perceived to be unique to LVAD-related ventricular tachycardia (VT) ablation such as vascular and LV access, signal filtering, catheter manoeuvrability within decompressed chambers, and electroanatomic mapping system interference. In some patients, the arrhythmogenic substrate might not be readily accessible by catheter ablation after LVAD implantation. In this regard, the peri-implantation period offers a unique opportunity to surgically address arrhythmogenic substrate and suppress future VT recurrences. This document aims to address specific aspects of the management of arrhythmias in LVAD patients focusing on anti-arrhythmic drug therapy and ablations., Competing Interests: Conflict of interest: O.A. serves as an advisor for Novartis, Boehringer Ingelheim, AstraZeneca, Merck Sharp & Dohme, Sanofi, Bayer, Pfizer, Amgen, Bristol Myers Squibb, Eli Lilly and reports consulting fees from Medical Consults: Restore -Medical, Cordio-Medical, and Boehringer Ingelheim. A.B-G. serves as an advisor for Abbott, AstraZeneca, Boehringer-Ingelheim, Bayer, Medtronic, Novartis, Roche Diagnostics, and Vifor. F.G. serves as an advisor for Abbott, FineHeart, AdjuCor, Corwave, Bayer, Astra-Zeneca, Ionis, Alnylam, and Roche. M.PE. reports research funding from Boehringer Ingelheim, Roche, SQ Innovations, Astra Zeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, Pharmacosmos, and consultancy for Abott, Akero, Applied Therapeutics, Amgen, AnaCardio, Biosensors, Boehringer Ingelheim, Corteria, Novartis, Astra Zeneca, Novo Nordisk, Abbvie, Bayer, Horizon Therapeutics, Foundry, Takeda, Cardiorentis, Pharmacosmos, Siemens, Eli Lilly, Vifor, New Amsterdam, Moderna, Teikoku, LIB Therapeutics, 3R Lifesciences, Reprieve, FIRE 1, Corvia, Regeneron. M.PA. reports fees from Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Novartis, Roche Diagnostics, and Vifor Pharma. P.P. reports speakers’ honoraria from Boston Scientific, Abbott, Medtronic, Biosense Webster, and Biotronik. F.S. reports speakers’ honoraria from Abbott, Biosense Webster, Boston Scientific, and Medtronic, and consulting fees from Inheart. Others report no relevant conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction and Objectives: Our aim was to describe the characteristics and outcomes of heart transplants in Spain., Methods: We analyzed trends in recipient and donor characteristics, recipient-donor interaction, surgical procedures, immunosuppression, and outcomes of patients included in the Spanish heart transplant registry from 2014 to 2023. Changes in survival were analyzed using the Kaplan-Meier method., Results: In 2023, 325 cardiac transplants were performed (4.5% more than in the previous year), with a total of 2987 procedures from 2014 to 2023. There was a trend toward performing more transplants in women (29.2%), with etiologies other than cardiomyopathy (32.6%), and with better pretransplant status (less hepatic [12.5%], renal [glomerular filtration rate, 81.5mL/min/1.73 m 2 ], and respiratory [8.7%] involvement). In 2023, the number of urgent transplants increased (44% of the total), especially those performed after circulatory support with extracorporeal membrane oxygenation (36% of total assistance), and transplants performed with donation after circulatory death (17.9%). Survival improved in the triennium from 2020 to 2022 compared with 2014 to 2016 (83.0% at 1 year from 2020-2022 vs 79.0% from 2014-2016)., Conclusions: The number of transplants performed in Spain showed an upward trend, with recipients with better clinical status and an increasing use of donation after circulatory death. Survival improved in the last triennium., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction and Objective: Clinical manifestations secondary to amyloid deposition in connective tissue may allow early detection of amyloidosis. We sought to identify the prevalence of connective tissue amyloidosis in patients undergoing orthopedic surgery and evaluate for cardiac involvement., Material and Methods: Descriptive cross-sectional study that included patients >50 years referred for orthopedic surgery at our center. A sample of the affected connective tissue was taken during the intervention to evaluate the presence of amyloid material. Those with confirmed amyloidosis were further evaluated with complementary tests for cardiac involvement., Results: Forty-eight patients were included. Mean age was 65.4 years and 41.7% were women. The most frequent surgery was supraspinatus tendon rupture (50%). Transthyretin amyloid deposits were detected in 2 patients (4.2%). The absence of variants in the protein gene established the diagnosis of ATTRwt in both cases. None of them presented cardiac involvement., Conclusions: In this study, 4.2% of patients referred for orthopedic surgery presented transthyretin amyloidosis in the affected connective tissue., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

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.)

Introduction and Objectives: The impact of preoperative left ventricular (LV) unloading on postoperative outcomes in patients bridged with venoarterial extracorporeal membrane oxygenation (VA-ECMO) to heart transplantation (HT) is unknown. Our aim was to compare posttransplant outcomes in patients bridged to HT with VA-ECMO, with or without the use of different mechanical strategies for LV decompression., Methods: We conducted a retrospective analysis of the postoperative outcomes of consecutive HT candidates bridged with VA-ECMO, with or without concomitant LV unloading. Patients were included from 16 Spanish centers from 2010 to 2020. The primary endpoint was 1-year post-HT survival, which was assessed using Cox regression., Results: Overall, 245 patients underwent high-emergency HT while supported with VA-ECMO. A mechanical strategy for LV unloading was used in 133 (54.3%) patients, with the intra-aortic balloon pump being the most commonly used method (n=112; 84.2%). One-year posttransplant survival was 74.4% in the LV unloading group and 59.8% in the control group (P=.025). In multivariate analyses, preoperative LV unloading was independently associated with lower 1-year mortality (adjusted HR, 0.50; 95%CI, 0.32-0.78; P=.003). This association was observed both in patients managed with an intra-aortic balloon pump alone (adjusted HR, 0.52; 95%CI, 0.32-0.84; P=.007) and with other strategies for mechanical LV unloading (adjusted HR, 0.43; 95%CI, 0.19-0.97; P=.042). No significant differences were found between groups regarding other postoperative complications., Conclusions: Preoperative LV unloading was independently associated with increased 1-year posttransplant survival in candidates bridged with VA-ECMO., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Despite guideline recommendations, many patients with heart failure (HF) do not receive target dosages of renin-angiotensin-aldosterone system inhibitors (RAASis) in clinical practice due, in part, to concerns about hyperkalemia (HK)., Methods and Results: This noninterventional, multinational, multicenter registry (NCT04864795; 111 sites in Europe and the USA) enrolled 2558 eligible adults with chronic HF (mostly with reduced ejection fraction [HFrEF]). Eligibility criteria included use of angiotensin-converting-enzyme inhibitor/angiotensin-II receptor blocker/angiotensin-receptor-neprilysin inhibitor, being a candidate for or treatment with a mineralocorticoid receptor antagonist, and increased risk of HK (eg, current serum potassium > 5.0 mmol/L), history of HK in the previous 24 months, or estimated glomerular filtration rate < 45 mL/min/1.73 m 2 ). Information on RAASi and other guideline-recommended therapies was collected retrospectively and prospectively (≥ 6 months). Patients were followed according to local clinical practice, without study-specific visits or interventions. The main objectives were to characterize RAASi treatment patterns compared with guideline recommendations, describe RAASi modifications following episodes of HK, and describe RAASi treatment in patients treated with patiromer. Baseline characteristics for the first 1000 patients are presented., Conclusions: CARE-HK is a multinational prospective HF registry designed to report on the management and outcomes of patients with HF at high risk for HK in routine clinical practice., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: We analysed baseline characteristics and guideline-directed medical therapy (GDMT) use and decisions in the European Society of Cardiology (ESC) Heart Failure (HF) III Registry., Methods and Results: Between 1 November 2018 and 31 December 2020, 10 162 patients with acute HF (AHF, 39%, age 70 [62-79], 36% women) or outpatient visit for HF (61%, age 66 [58-75], 33% women), with HF with reduced (HFrEF, 57%), mildly reduced (HFmrEF, 17%) or preserved (HFpEF, 26%) ejection fraction were enrolled from 220 centres in 41 European or ESC-affiliated countries. With AHF, 97% were hospitalized, 2.2% received intravenous treatment in the emergency department, and 0.9% received intravenous treatment in an outpatient clinic. AHF was seen by most by a general cardiologist (51%) and outpatient HF most by a HF specialist (48%). A majority had been hospitalized for HF before, but 26% of AHF and 6.1% of outpatient HF had de novo HF. Baseline use, initiation and discontinuation of GDMT varied according to AHF versus outpatient HF, de novo versus pre-existing HF, and by ejection fraction. After the AHF event or outpatient HF visit, use of any renin-angiotensin system inhibitor, angiotensin receptor-neprilysin inhibitor, beta-blocker, mineralocorticoid receptor antagonist and loop diuretics was 89%, 29%, 92%, 78%, and 85% in HFrEF; 89%, 9.7%, 90%, 64%, and 81% in HFmrEF; and 77%, 3.1%, 80%, 48%, and 80% in HFpEF., Conclusion: Use and initiation of GDMT was high in cardiology centres in Europe, compared to previous reports from cohorts and registries including more primary care and general medicine and regions more local or outside of Europe and ESC-affiliated countries., (© 2024 European Society of Cardiology.)

Background and Objective: Hyperkalemia (HK) is an electrolyte disturbance in the concentration of potassium ions (K + ), whose risk increases in patients with chronic kidney disease (CKD) or heart failure (HF) and/or in patients being treated with renin-angiotensin-aldosterone system inhibitors (RAASi). The new oral K + chelators offer a safe and effective treatment to maintain normokalemia in these patients. The objective of the analysis is to estimate the cost-effectiveness of sodium zirconium cyclosilicate (SZC) for the treatment of chronic HK in patients with CKD or HF versus standard treatment (calcium polystyrene sulfonate and lifestyle modifications) from the perspective of the Spanish National Health System., Materials and Methods: Two microsimulation models reflecting the natural history of CKD and HF were used. In both models, K + levels were simulated individually. Based on efficacy (reduction of K + levels), quality of life of patients (utilities according to health states, and disutilities of events derived from each pathology and adverse events [AEs] of treatment) and costs considered (cost of treatment for HK, of RAASi treatment and its modification, health states, management of events derived from each pathology, HK episodes, and AEs treatment) (, 2022), clinical benefit (quality-adjusted life years [QALYs]) and cost results were obtained. A time horizon of the patient's lifetime was used and a discount rate of 3% was applied for costs and outcomes., Results: SZC is a more effective option in both pathologies, with a difference in QALYs of 0.476 in CKD and 0.978 in HF compared to standard treatment, and it represents an incremental cost of 3,616 and 14,749, respectively, obtaining an incremental cost-utility ratio of 7,605/QALY in CKD and 15,078/QALY in HF., Conclusions: SZC is a cost-effective alternative for the treatment of HK in patients with CKD or HF, taking into account the reference efficiency values commonly used in Spain., (Copyright © 2024. Published by Elsevier España, S.L.U.)

The first-generation Molecular Microscope (MMDx) system for heart transplant endomyocardial biopsies used expression of rejection-associated transcripts (RATs) to diagnose not only T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) but also acute injury. However, the ideal system should detect rejection without being influenced by injury, to permit analysis of the relationship between rejection and parenchymal injury. To achieve this, we developed a new rejection classification in an expanded cohort of 3230 biopsies: 1641 from INTERHEART (ClinicalTrials.gov NCT02670408), plus 1589 service biopsies added to improve the power of the machine learning algorithms. The new system used 6 rejection classifiers instead of RATs and generated 7 rejection archetypes: No rejection, 48%; Minor, 24%; TCMR1, 2.3%; TCMR2, 2.7%; TCMR/mixed, 2.7%; early-stage ABMR, 3.9%; and fully developed ABMR, 16%. Using rejection classifiers eliminated cross-reactions with acute injury, permitting separate assessment of rejection and injury. TCMR was associated with severe-recent injury and late atrophy-fibrosis and rarely had normal parenchyma. ABMR was better tolerated, seldom producing severe injury, but in later biopsies was often associated with atrophy-fibrosis, indicating long-term risk. Graft survival and left ventricular ejection fraction were reduced not only in hearts with TCMR but also in hearts with severe-recent injury and atrophy-fibrosis, even without rejection., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction and Objectives: The tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/SPAP) ratio is a noninvasive surrogate of right ventricular to pulmonary circulation that has prognostic implications in patients with heart failure (HF) or pulmonary hypertension. Our purpose was to evaluate the prognostic value of the TAPSE/SPAP ratio in patients with cardiac amyloidosis., Methods: We used the database of the AMIGAL study, a prospective, observational registry of patients with cardiac amyloidosis recruited in 7 hospitals of the Autonomous Community of Galicia, Spain, from January 1, 2018 to October 31, 2022. We selected patients whose baseline TAPSE/SPAP ratio was calculated with transthoracic echocardiography. Long-term survival and survival free of HF hospitalization were assessed by means of 5 different multivariable Cox regression models. Median follow-up was 680 days., Results: We studied 233 patients with cardiac amyloidosis, among whom 209 (89.7%) had transthyretin type. The baseline TAPSE/SPAP ratio correlated significantly with clinical outcomes. Depending on the multivariable model considered, the adjusted hazard ratios estimated per 0.1mm/mmHg increase of baseline TAPSE/SPAP ratio ranged from 0.76 to 0.84 for all-cause mortality. Similarly, the ratios for all-cause mortality of HF hospitalization ranged from 0.79 to 0.84. The addition of the baseline TAPSE/SPAP ratio to the predictive model of the United Kingdom National Amyloidosis Centre resulted in an increase in Harrell's c-statistic from 0.662 to 0.705 for all-cause mortality and from 0.668 to 0.707 for all-cause mortality or HF hospitalization., Conclusions: Reduced TAPSE/SPAP ratio is an independent adverse prognostic marker in patients with cardiac amyloidosis., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction and Objetives: Cardiac amyloidosis (CA) is a disorder associated with high number of hospital admissions. Given the scarce information available, we propose an analysis of the incidence and causes of hospitalization in this disease., Material and Methods: One hundred and forty-three patients [128 by transthyretin (ATTR-CA) and 15 by light chains (AL-CA)] included in Registro de Amiloidosis Cardiaca de Galicia (AMIGAL) were evaluated, including all hospitalizations., Results: During a median follow-up of 959 days there were 179 unscheduled hospitalizations [incidence rate (IR) 512.6 admissions per 1000 patients-year], most common due to cardiovascular reasons (n=109, IR 312.2). Most frequent individual cause of hospitalization was heart failure (n=87, TI 249.2). AL-CA was associated with a higher IR of unscheduled hospitalizations than ATTR-CA (IR 781 vs. 483.2; HR 1.62; p=0,029) due to non-cardiovascular admissions (IR 376 vs. 181.2; HR 2.07; p=0.027). Unscheduled admission-free survival at 1 and 3 years in AL-CA was inferior than in ATTR-CA (46.7% and 20.0% vs. 73.4% and 35.2%, respectively; p=0.021)., Conclusions: CA was associated with high incidence of hospitalizations, being heart failure the most frequent individual cause; unscheduled admission-free survival in AL-CA was lower than in ATTR-CA due mostly to non-cardiovascular admissions., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

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.)

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

Background: We explored the changes in gene expression correlating with dysfunction and graft failure in endomyocardial biopsies., Methods: Genome-wide microarrays (19,462 genes) were used to define mRNA changes correlating with dysfunction (left ventricular ejection fraction [LVEF] ≤ 55) and risk of graft loss within 3 years postbiopsy. LVEF data was available for 1,013 biopsies and survival data for 779 patients (74 losses). Molecular classifiers were built for predicting dysfunction (LVEF ≤ 55) and postbiopsy 3-year survival., Results: Dysfunction is correlated with dedifferentiation-decreased expression of normal heart transcripts, for example, solute carriers, along with increased expression of inflammation genes. Many genes with reduced expression in dysfunction were matrix genes such as fibulin 1 and decorin. Gene ontology (GO) categories suggested matrix remodeling and inflammation, not rejection. Genes associated with the risk of failure postbiopsy overlapped dysfunction genes but also included genes affecting microcirculation, for example, arginase 2, which reduces NO production, and endothelin 1. GO terms also reflected increased glycolysis and response to hypoxia, but decreased VEGF and angiogenesis pathways. T cell-mediated rejection was associated with reduced survival and antibody-mediated rejection with relatively good survival, but the main determinants of survival were features of parenchymal injury. Both dysfunction and graft loss were correlated with increased biopsy expression of BNP (gene NPPB). Survival probability classifiers divided hearts into risk quintiles, with actuarial 3-year postbiopsy survival >95% for the highest versus 50% for the lowest., Conclusions: Dysfunction in transplanted hearts reflects dedifferentiation, decreased matrix genes, injury, and inflammation. The risk of short-term loss includes these changes but is also associated with microcirculation abnormalities, glycolysis, and response to hypoxia., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Purpose: To analyze the impact of chronic obstructive pulmonary disease (COPD) and bronchial asthma on therapeutic management and prognosis of patients with heart failure (HF)., Methods: Analysis of the information collected in a clinical registry of patients referred to a specialized HF unit from January-2010 to June-2012. Clinical profile, treatment and prognosis of patients was evaluated, according to the presence of COPD or asthma. Survival analyses were conducted by means of Kaplan-Meier and Cox's methods. Median follow-up was 1493 days., Results: We studied 2577 patients, of which 251 (9.7%) presented COPD and 96 (3.7%) bronchial asthma. Significant differences among study groups were observed regarding to the prescription of beta-blockers (COPD=89.6%; asthma=87.5%; no bronchopathy=94.1%; p=0.002) and SGLT2 inhibitors (COPD=35.1%; asthma=50%; no bronchopathy=38.3%; p=0.036). Also, patients with bronchial disease received less frequently a defibrillator (COPD=20.3%; asthma=20.8%; no broncopathy=29%; p=0.004). COPD was independently associated with increased risk of all-cause mortality (HR=1.64; 95% CI 1.33-2.02), all-cause death or HF admission (HR=1.47; 95% CI 1.22-1.76) and cardiovascular death or heart transplantation (HR=1.39; 95% CI 1.08-1.79) as compared with patients with no bronchopathy. Bronchial asthma was not significantly associated with increased risk of adverse outcomes., Conclusions: COPD, but not asthma, is an adverse independent prognostic factor in patients with HF., (Copyright © 2024 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Aims: To evaluate the effect of long-term tafamidis treatment on health-related quality of life (HRQoL) in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) enrolled in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and long-term extension (LTE) study., Methods and Results: We examined change from baseline in Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS) and clinical summary (KCCQ-CS) scores in patients who received tafamidis meglumine 80 mg for 30 months in ATTR-ACT and tafamidis (meglumine 80 mg or bioequivalent free acid 61 mg) for 30 months in the LTE study, and in patients who received placebo for 30 months in ATTR-ACT and tafamidis for 30 months in the LTE study. In ATTR-ACT, 176 and 177 patients were randomized to tafamidis 80 mg and placebo, respectively. Patients who continuously received tafamidis had a 6- to 7-point reduction in least squares (LS) mean (standard error) KCCQ-OS and KCCQ-CS scores at month 30 (-6.25 [1.53] and -7.48 [1.39]), with little or no further decline over the next 30 months (-5.92 [1.77] and -9.21 [1.88] at month 60). Patients who received placebo in ATTR-ACT had a 20-point reduction in LS mean KCCQ-OS and KCCQ-CS scores at month 30 (-19.60 [1.94] and -19.90 [2.01]), but the decline slowed after initiating tafamidis (-24.70 [3.04] and -25.30 [3.36] at month 60)., Conclusion: Tafamidis reduced HRQoL decline in patients with ATTR-CM. Patients continuously treated with tafamidis for 60 months demonstrated stabilized HRQoL. In patients who initially received placebo in ATTR-ACT, tafamidis reduced the decline in HRQoL during the LTE study., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

What Is This Summary About?: This summary explains some results of a study called ATTR-ACT and its ongoing long-term extension study that were published in the European Journal of Heart Failure . The purpose of ATTR-ACT was to find out if a drug called tafamidis is an effective treatment for people with a heart condition called transthyretin amyloid cardiomyopathy (ATTR-CM). People took tafamidis or placebo for up to 2.5 years in ATTR-ACT (the initial study). A placebo looks like the study medicine but does not contain any active ingredients. After people completed the initial study, they could take part in the extension study. An extension study allows people to continue receiving treatment after the original clinical study ends and helps researchers understand how well a treatment works over a longer time period. This extension study allows people to receive tafamidis for up to an additional 5 years. People who took placebo in the initial study now receive tafamidis. People who took tafamidis in the initial study continue tafamidis treatment. Researchers looked at changes in peoples' ability to enjoy life ('quality of life') and heart failure symptoms since they started ATTR-ACT. Results are available for the first 2.5 years of the extension study., What Are the Key Takeaways?: During the initial study, there was less worsening of quality of life and heart failure symptoms in people who took tafamidis compared to people who took placebo. In the extension study, quality of life and heart failure symptoms were maintained or nearly maintained in people who took tafamidis in the initial study. In people who started tafamidis in the extension study, quality of life and heart failure symptoms continued to worsen, but the worsening slowed down., What Were the Main Conclusions Reported by the Researchers?: Tafamidis slows the worsening of quality of life and heart failure symptoms in people with ATTR-CM. People with ATTR-CM should start treatment early to receive the most benefit. Clinical Trial Registration: NCT01994889 (ATTR-ACT) (ClinicalTrials.gov).

Aims: Aims were to evaluate (1) reclassification of patients from heart failure with mildly reduced (HFmrEF) to reduced (HFrEF) ejection fraction when an EF = 40% was considered as HFrEF, (2) role of EF digit bias, ie, EF reporting favouring 5% increments; (3) outcomes in relation to missing and biased EF reports, in a large multinational HF registry., Methods and Results: Of 25,154 patients in the European Society of Cardiology (ESC) HF Long-Term registry, 17% had missing EF and of those with available EF, 24% had HFpEF (EF≥50%), 21% HFmrEF (40%-49%) and 55% HFrEF (<40%) according to the 2016 ESC guidelines´ classification. EF was "exactly" 40% in 7%, leading to reclassifying 34% of the HFmrEF population defined as EF = 40% to 49% to HFrEF when applying the 2021 ESC Guidelines classification (14% had HFmrEF as EF = 41% to 49% and 62% had HFrEF as EF≤40%). EF was reported as a value ending with 0 or 5 in ∼37% of the population. Such potential digit bias was associated with more missing values for other characteristics and higher risk of all-cause death and HF hospitalization. Patients with missing EF had higher risk of all-cause and CV mortality, and HF hospitalization compared to those with recorded EF., Conclusions: Many patients had reported EF = 40%. This led to substantial reclassification of EF from old HFmrEF (40%-49%) to new HFrEF (≤40%). There was considerable digit bias in EF reporting and missing EF reporting, which appeared to occur not at random and may reflect less rigorous overall care and worse outcomes., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Document Reviewers: Rudolf A. de Boer (CPG Review Co-ordinator) (Netherlands), P. Christian Schulze (CPG Review Co-ordinator) (Germany), Elena Arbelo (Spain), Jozef Bartunek (Belgium), Johann Bauersachs (Germany), Michael A. Borger (Germany), Sergio Buccheri (Sweden), Elisabetta Cerbai (Italy), Erwan Donal (France), Frank Edelmann (Germany), Gloria Färber (Germany), Bettina Heidecker (Germany), Borja Ibanez (Spain), Stefan James (Sweden), Lars Køber (Denmark), Konstantinos C. Koskinas (Switzerland), Josep Masip (Spain), John William McEvoy (Ireland), Robert Mentz (United States of America), Borislava Mihaylova (United Kingdom), Jacob Eifer Møller (Denmark), Wilfried Mullens (Belgium), Lis Neubeck (United Kingdom), Jens Cosedis Nielsen (Denmark), Agnes A. Pasquet (Belgium), Piotr Ponikowski (Poland), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Bianca Rocca (Italy), Xavier Rossello (Spain), Leyla Elif Sade (United States of America/Türkiye), Hannah Schaubroeck (Belgium), Elena Tessitore (Switzerland), Mariya Tokmakova (Bulgaria), Peter van der Meer (Netherlands), Isabelle C. Van Gelder (Netherlands), Mattias Van Heetvelde (Belgium), Christiaan Vrints (Belgium), Matthias Wilhelm (Switzerland), Adam Witkowski (Poland), and Katja Zeppenfeld (Netherlands) All experts involved in the development of this Focused Update have submitted declarations of interest. These have been compiled in a report and simultaneously published in a supplementary document to the Focused Update. The report is also available on the ESC website www.escardio.org/guidelines See the European Heart Journal online for supplementary documents that include evidence tables., (© 2024 European Society of Cardiology.)

Introduction and Objectives: We aimed to describe the clinical outcomes of the use of the CentriMag acute circulatory support system as a bridge to emergency heart transplantation (HTx)., Methods: We conducted a descriptive analysis of the clinical outcomes of consecutive HTx candidates included in a multicenter retrospective registry who were treated with the CentriMag device, configured either for left ventricular support (LVS) or biventricular support (BVS). All patients were listed for high-priority HTx. The study assessed the period 2010 to 2020 and involved 16 transplant centers around Spain. We excluded patients treated with isolated right ventricular support or venoarterial extracorporeal membrane oxygenation without LVS. The primary endpoint was 1-year post-HTx survival., Results: The study population comprised 213 emergency HTx candidates bridged on CentriMag LVS and 145 on CentriMag BVS. Overall, 303 (84.6%) patients received a transplant and 53 (14.8%) died without having an organ donor during the index hospitalization. Median time on the device was 15 days, with 66 (18.6%) patients being supported for> 30 days. One-year posttransplant survival was 77.6%. Univariable and multivariable analyses showed no statistically significant differences in pre- or post-HTx survival in patients managed with BVS vs LVS. Patients managed with BVS had higher rates of bleeding, need for transfusion, hemolysis and renal failure than patients managed with LVS, while the latter group showed a higher incidence of ischemic stroke., Conclusions: In a setting of candidate prioritization with short waiting list times, bridging to HTx with the CentriMag system was feasible and resulted in acceptable on-support and posttransplant outcomes., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Heart transplant (HT) remains the best therapeutic option for patients with advanced heart failure (HF). The allocation criteria aim to guarantee equitable access to HT and prioritize patients with a worse clinical status. To review the HT allocation criteria, the Heart Failure Association of the Spanish Society of Cardiology (HFA-SEC), the Spanish Society of Cardiovascular and Endovascular Surgery (SECCE) and the National Transplant Organization (ONT), organized a consensus conference involving adult and pediatric cardiologists, adult and pediatric cardiac surgeons, transplant coordinators from all over Spain, and physicians and nurses from the ONT. The aims of the consensus conference were as follows: a) to analyze the organization and management of patients with advanced HF and cardiogenic shock in Spain; b) to critically review heart allocation and priority criteria in other transplant organizations; c) to analyze the outcomes of patients listed and transplanted before and after the modification of the heart allocation criteria in 2017; and d) to propose new heart allocation criteria in Spain after an analysis of the available evidence and multidisciplinary discussion. In this article, by the HFA-SEC, SECCE and the ONT we present the results of the analysis performed in the consensus conference and the rationale for the new heart allocation criteria in Spain., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Aims: Atrial fibrillation (AF) worsens the prognosis of patients with heart failure (HF). Successful treatments are still very scarce for those with permanent AF and preserved (HFpEF) or mildly reduced (HFmrEF) ejection fraction. In this study, the long-term benefits and safety profile of heart rate regularization through left-bundle branch pacing (LBBP) and atrioventricular node ablation (AVNA) will be explored in comparison with pharmacological rate-control strategy., Methods and Results: The PACE-FIB trial is a multicentre, prospective, open-label, randomized (1:1) clinical study that will take place between March 2022 and February 2027. A total of 334 patients with HFpEF/HFmrEF and permanent AF will receive either LBBP followed by AVNA (intervention arm) or optimal pharmacological treatment for heart rate control according to European guideline recommendations (control arm). All patients will be followed up for a minimum of 36 months. The primary outcome measure will be the composite of all-cause mortality, HF hospitalization, and worsening HF at 36 months. Other secondary efficacy and safety outcome measures such as echocardiographic parameters, functional status, and treatment-related adverse events, among others, will be analysed too., Conclusion: LBBP is a promising stimulation mode that may foster the clinical benefit of heart rate regularization through AV node ablation compared with pharmacological rate control. This is the first randomized trial specifically addressing the long-term efficacy and safety of this pace-and-ablate strategy in patients with HFpEF/HFmrEF and permanent AF., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Heart failure outcomes remain poor despite advances in therapy. The European Society of Cardiology Heart Failure III Registry (ESC HF III Registry) aims to characterize HF clinical features and outcomes and to assess implementation of guideline-recommended therapy in Europe and other ESC affiliated countries., Methods: Between 1 November 2018 and 31 December 2020, 10 162 patients with chronic or acute/worsening HF with reduced, mildly reduced, or preserved ejection fraction were enrolled from 220 centres in 41 European or ESC affiliated countries. The ESC HF III Registry collected data on baseline characteristics (hospital or clinic presentation), hospital course, diagnostic and therapeutic decisions in hospital and at the clinic visit; and on outcomes at 12-month follow-up. These data include demographics, medical history, physical examination, biomarkers and imaging, quality of life, treatments, and interventions - including drug doses and reasons for non-use, and cause-specific outcomes., Conclusion: The ESC HF III Registry will provide comprehensive and unique insight into contemporary HF characteristics, treatment implementation, and outcomes, and may impact implementation strategies, clinical discovery, trial design, and public policy., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction and Objectives: The Spanish heart transplant registry updates its data annually. The current update presents the data for the year 2022., Methods: We describe the main clinical characteristics, treatments received, and survival outcomes including procedures performed in 2022, along with their trends since 2013., Results: In 2022, 311 cardiac transplants were performed, representing a 3.0% increase compared with 2021. Compared with previous years, no significant changes in demographic and clinical characteristics were observed in 2022, confirming the trends identified in the last decade. These trends indicate a decrease in urgent procedures and the use of circulatory support, particularly ventricular assist devices. In the last decade, survival rates at 1 and 3 years were 81.4% and 73.4% respectively, with a slight, nonsignificant improvement., Conclusions: In the last decade, there has been a stabilization in the characteristics of heart transplant procedures and their outcomes. This trial was registered at ClinicalTrial.gov (Identifier: NCT03015311)., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

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

Aims: To evaluate the prevalence and associations of non-cardiac comorbidities (NCCs) with in-hospital and post-discharge outcomes in acute heart failure (AHF) across the ejection fraction (EF) spectrum., Methods and Results: The 9326 AHF patients from European Society of Cardiology (ESC)-Heart Failure Association (HFA)-EURObservational Research Programme Heart Failure Long-Term Registry had complete information for the following 12 NCCs: anaemia, chronic obstructive pulmonary disease (COPD), diabetes, depression, hepatic dysfunction, renal dysfunction, malignancy, Parkinson's disease, peripheral vascular disease (PVD), rheumatoid arthritis, sleep apnoea, and stroke/transient ischaemic attack (TIA). Patients were classified by number of NCCs (0, 1, 2, 3, and ≥4). Of the AHF patients, 20.5% had no NCC, 28.5% had 1 NCC, 23.1% had 2 NCC, 15.4% had 3 NCC, and 12.5% had ≥4 NCC. In-hospital and post-discharge mortality increased with number of NCCs from 3.0% and 18.5% for 1 NCC to 12.5% and 36% for ≥4 NCCs.Anaemia, COPD, PVD, sleep apnoea, rheumatoid arthritis, stroke/TIA, Parkinson, and depression were more prevalent in HF with preserved EF (HFpEF). The hazard ratio (95% confidence interval) for post-discharge death for each NCC was for anaemia 1.6 (1.4-1.8), diabetes 1.2 (1.1-1.4), kidney dysfunction 1.7 (1.5-1.9), COPD 1.4 (1.2-1.5), PVD 1.2 (1.1-1.4), stroke/TIA 1.3 (1.1-1.5), depression 1.2 (1.0-1.5), hepatic dysfunction 2.1 (1.8-2.5), malignancy 1.5 (1.2-1.8), sleep apnoea 1.2 (0.9-1.7), rheumatoid arthritis 1.5 (1.1-2.1), and Parkinson 1.4 (0.9-2.1). Anaemia, kidney dysfunction, COPD, and diabetes were associated with post-discharge mortality in all EF categories, PVD, stroke/TIA, and depression only in HF with reduced EF, and sleep apnoea and malignancy only in HFpEF., Conclusion: Multiple NCCs conferred poor in-hospital and post-discharge outcomes. Ejection fraction categories had different prevalence and risk profile associated with individual NCCs., Competing Interests: Conflict of interest: O. Chioncel declare no conflict of interest related to present work; ESC meeting support from Servier. L. Benson declare no conflict of interest. M. Crespo-Leiro reports unrelated to the present work: consultancy or speaker's honoraria from Novartis, AstraZeneca, Boehringer Ingelheim, Abbott, Medtronic, CareDx, Astellas and Vifor Pharma. S.D. Anker reports unrelated to the present work: Grants or contracts: Vifor Int, Abbott Vascular; Consulting fees: CVRx, Amgen, Respicardia, Novo Nordisk, Brahms, Novartis, Sanofi, Cordio; Leadership or fiduciary role in other board: Abbott Vascular, Astra Zeneca, Bayer AG, Bioventrix, Boehringer Ingelheim, Cardiac Dimension, Cardior, Impulse Dynamics, Janssen, Occlutech, Servier, Vifor Int, and V-Wave. A.J.S. Coats reports unrelated to the present work: speaker's honoraria from: Astra Zeneca, Bayer, Boehringer Ingelheim, Edwards, Menarini, Novartis, Servier, Vifor, Abbott, Actimed, Arena, Cardiac Dimensions, Corvia, CVRx, Enopace, ESN Cleer, Faraday, Impulse Dynamics, Respicardia, and Viatris. G. Filippatos reports lecture fees and/or committee membership in trials sponsored by Bayer, Vifor, Medtronic, Novartis, Servier, Boehringer Ingelheim, and research support from the European Union. T. McDonagh reports unrelated to the present work: speaker's honoraria from Abbot, Astra Zeneca, Boeringher Ingelheim and Edwards. C. Margineanu none related to the present work. A. Mebazaa reports unrelated to the present work: Grants or contracts from and consulting fees from Roche, 4TEEN4, Corteria; speaker's honoraria from MSD; Patents: S-Form Pharma. M. Metra reports personal fees from Amgen, AstraZeneca, Abbott Vascular, Bayer, Edwards Therapeutics, Livanova, Vifor Pharma, as member of Trials' Committees or advisory boards or for speeches at sponsored meetings in the last 3 years. M. Piepoli reports unrelated to the present work: consultancy, speaker's, institutional fees from Astra-Zeneca, Boehringer- Ingelheim, CHF solution, Menarini, Novartis, Servier M. Adammo reports speaker fees from Abbott Vascular and Medtronic. G.M.C. Rosano declare no conflict of interest. F. Ruschitzka has not received personal payments by pharmaceutical companies or device manufacturers in the last 3 years (remuneration for the time spent in activities, such as participation as steering committee member of clinical trials and member of the Pfizer Research Award selection committee in Switzerland, were made directly to the University of Zurich). The Department of Cardiology (University Hospital of Zurich/University of Zurich) reports research-, educational- and/or travel grants from Abbott, Amgen, Astra Zeneca, Bayer, Berlin Heart, B. Braun, Biosense Webster, Biosensors Europe AG, Biotronik, BMS, Boehringer Ingelheim, Boston Scientific, Bracco, Cardinal Health Switzerland, Corteria, Daiichi, Diatools AG, Edwards Lifesciences, Guidant Europe NV (BS), Hamilton Health Sciences, Kaneka Corporation, Kantar, Labormedizinisches Zentrum, Medtronic, MSD, Mundipharma Medical Company, Novartis, Novo Nordisk, Orion, Pfizer, Quintiles Switzerland Sarl, Roche Diagnostics, Sahajanand IN, Sanofi, Sarstedt AG, Servier, SIS Medical, SSS International Clinical Research, Terumo Deutschland, Trama Solutions, V- Wave, Vascular Medical, Vifor, Wissens Plus, ZOLL. The research and educational grants do not impact on Prof. Ruschitzka`s personal remuneration. G. Savarese reports unrelated to the present work: Grants or contracts: Vifor Pharma, Boehringer Ingelheim, Astra Zeneca, Merck, Cytokinetics; Consulting fees: Societa' Prodotti Antibiotici, Medical Education Global Solutions, Genesis, Agence Recherche (ANR); speaker's honoraria: Servier, Cytokinetics, Medtronic, Dynamicom Education, Vifor Pharma; Support for attending meetings: Boehringer Ingelheim; Data Safety Monitoring Bord or Advisory Board: Astra Zeneca, Uppsala Clinical Research Center, Servier. P. Seferovic reports unrelated to the present work: speaker's honoraria from Servier, Astra Zeneca, Menarini, Boehringer Ingelheim, Novartis and Roche diagnostic. M. Volterrani: none related to the present work. R. Ferrari reports unrelated to the present work: speaker's honoraria and support for attending meetings: Servier International, Merck Serono, Lupin, Sunpharma, Reddys Ltd; leadership or fiduciary role in other board: Scientific Director of Medical Trial Analysis. A. Maggioni: personal fees from AstraZeneca, Bayer, Fresenius, Novartis, outside the submitted work. L.H. Lund is supported by Supported by Karolinska Institutet, the Swedish Research Council [grant 523-2014-2336], the Swedish Heart Lung Foundation [grants 20150557, 20190310], and the Stockholm County Council [grants 20170112, 20190525] and reports unrelated to the present work: Grants: AstraZeneca, Vifor, Boston Scientific, Boehringer Ingelheim, Novartis, MSD; Consulting: Vifor, AstraZeneca, Bayer, Pharmacosmos, MSD, MedScape, Sanofi, Lexicon, Myokardia, Boehringer Ingelheim, Servier, Edwards Life Sciences, Alleviant; Speaker's honoraria: Abbott, OrionPharma, MedScape, Radcliffe, AstraZeneca, Novartis, Boehringer Ingelheim, Bayer; Patent: AnaCardio; Stock ownership: AnaCardio., (© 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.)

Aims: To comprehensively assess hyponatraemia in acute heart failure (AHF) regarding prevalence, associations, hospital course, and post-discharge outcomes., Methods and Results: Of 8298 patients in the European Society of Cardiology Heart Failure Long-Term Registry hospitalized for AHF with any ejection fraction, 20% presented with hyponatraemia (serum sodium <135 mmol/L). Independent predictors included lower systolic blood pressure, estimated glomerular filtration rate (eGFR) and haemoglobin, along with diabetes, hepatic disease, use of thiazide diuretics, mineralocorticoid receptor antagonists, digoxin, higher doses of loop diuretics, and non-use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta-blockers. In-hospital death occurred in 3.3%. The prevalence of hyponatraemia and in-hospital mortality with different combinations were: 9% hyponatraemia both at admission and discharge (hyponatraemia Yes/Yes, in-hospital mortality 6.9%), 11% Yes/No (in-hospital mortality 4.9%), 8% No/Yes (in-hospital mortality 4.7%), and 72% No/No (in-hospital mortality 2.4%). Correction of hyponatraemia was associated with improvement in eGFR. In-hospital development of hyponatraemia was associated with greater diuretic use and worsening eGFR but also more effective decongestion. Among hospital survivors, 12-month mortality was 19% and adjusted hazard ratios (95% confidence intervals) were for hyponatraemia Yes/Yes 1.60 (1.35-1.89), Yes/No 1.35 (1.14-1.59), and No/Yes 1.18 (0.96-1.45). For death or heart failure hospitalization they were 1.38 (1.21-1.58), 1.17 (1.02-1.33), and 1.09 (0.93-1.27), respectively., Conclusion: Among patients with AHF, 20% had hyponatraemia at admission, which was associated with more advanced heart failure and normalized in half of patients during hospitalization. Admission hyponatraemia (possibly dilutional), especially if it did not resolve, was associated with worse in-hospital and post-discharge outcomes. Hyponatraemia developing during hospitalization (possibly depletional) was associated with lower risk., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The reported prevalence of donor-transmitted coronary artery disease (TCAD) in heart transplantation (HT) is variable, and its prognostic impact remains unclear., Objectives: The goal of this study was to characterize TCAD in a contemporary multicentric cohort and to study its prognostic relevance., Methods: This was a retrospective study of consecutive patients >18 years old who underwent HT in 11 Spanish centers from 2008 to 2018. Only patients with a coronary angiography (c-angio) within the first 3 months after HT were studied. Significant TCAD (s-TCAD) was defined as any stenosis ≥50% in epicardial coronary arteries, and nonsignificant TCAD (ns-TCAD) as stenosis <50%. Clinical outcomes were assessed by means of Cox regression and competing risks regression. Patients were followed-up for a median period of 6.3 years after c-angio., Results: From a cohort of 1,918 patients, 937 underwent c-angio. TCAD was found in 172 patients (18.3%): s-TCAD in 65 (6.9%) and ns-TCAD in 107 (11.4%). Multivariable Cox regression analysis did not show a statistically significant association between s-TCAD and all-cause mortality (adjusted HR: 1.44; 95% CI: 0.89-2.35; P = 0.141); however, it was an independent predictor of cardiovascular mortality (adjusted HR: 2.25; 95% CI: 1.20-4.19; P = 0.011) and the combined event cardiovascular death or nonfatal MACE (adjusted HR: 2.42; 95% CI: 1.52-3.85; P < 0.001). No statistically significant impact of ns-TCAD on clinical outcomes was detected. The results were similar when reassessed by means of competing risks regression., Conclusions: TCAD was not associated with reduced survival in patients alive and well enough to undergo post-HT angiography within the first 3 months; however, s-TCAD patients showed increased risk of cardiovascular death and MACE., Competing Interests: Funding Support and Author Disclosures Dr Couto-Mallón has received a research grant from the Fundación Mutua Madrileña, Spain (XVI Annual announcement, year 2019), which supplied funding for the present study. This research project was co-financed with European Union Regional Development Funds (EURDF), supplied through the Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness. All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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

Aim: Mitral regurgitation (MR) and tricuspid regurgitation (TR) are common in patients with heart failure (HF). The aim of this study was to investigate prevalence, clinical characteristics and outcomes of patients with or without isolated or combined MR and TR across the entire HF spectrum., Methods and Results: The ESC-HFA EORP HF Long-Term Registry is a prospective, multicentre, observational study including patients with HF and 1-year follow-up data. Outpatients without aortic valve disease were included and stratified according to isolated or combined moderate/severe MR and TR. Among 11 298 patients, 7541 (67%) had no MR/TR, 1931 (17%) isolated MR, 616 (5.5%) isolated TR and 1210 (11%) combined MR/TR. Baseline characteristics were differently distributed across MR/TR categories. Compared to HF with reduced ejection fraction, HF with mildly reduced ejection fraction was associated with a lower risk of isolated MR (odds ratio [OR] 0.69; 95% confidence interval [CI] 0.60-0.80), and distinctly lower risk of combined MR/TR (OR 0.51; 95% CI 0.41-0.62). HF with preserved ejection fraction (HFpEF) was associated with a distinctly lower risk of isolated MR (OR 0.42; 95% CI 0.36-0.49), and combined MR/TR (OR 0.59; 95% 0.50-0.70), but a distinctly increased risk of isolated TR (OR 1.94; 95% CI 1.61-2.33). All-cause death, cardiovascular death, HF hospitalization and combined outcomes occurred more frequently in combined MR/TR, isolated TR and isolated MR versus no MR/TR. The highest incident rates were observed in isolated TR and combined MR/TR., Conclusion: In a large cohort of outpatients with HF, prevalence of isolated and combined MR and TR was relatively high. Isolated TR was driven by HFpEF and was burdened by an unexpectedly poor outcome., (© 2023 European Society of Cardiology.)

Aims: To assess the prevalence, clinical characteristics, and outcomes of patients with heart failure (HF) with or without moderate to severe aortic valve disease (AVD) (aortic stenosis [AS], aortic regurgitation [AR], mixed AVD [MAVD])., Methods and Results: Data from the prospective ESC HFA EORP HF Long-Term Registry including both chronic and acute HF were analysed. Of 15 216 patients with HF (62.5% with reduced ejection fraction, HFrEF; 14.0% with mildly reduced ejection fraction, HFmrEF; 23.5% with preserved ejection fraction, HFpEF), 706 patients (4.6%) had AR, 648 (4.3%) AS and 234 (1.5%) MAVD. The prevalence of AS, AR and MAVD was 6%, 8%, and 3% in HFpEF, 6%, 3%, and 2% in HFmrEF and 4%, 3%, and 1% in HFrEF. The strongest associations were observed for age and HFpEF with AS, and for left ventricular end-diastolic diameter with AR. AS (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.23-1.67), and MAVD (adjusted HR 1.37, 95% CI 1.07-1.74) but not AR (adjusted HR 1.13, 95% CI 0.96-1.33) were independently associated with the 12-month composite outcome of cardiovascular death and HF hospitalization. The associations between AS and the composite outcome were observed regardless of ejection fraction category., Conclusions: In the ESC HFA EORP HF Long-Term Registry, one in 10 patients with HF had AVD, with AS and MAVD being especially common in HFpEF and AR being similarly distributed across all ejection fraction categories. AS and MAVD, but not AR, were independently associated with increased risk of in-hospital mortality and 12-month composite outcome, regardless of ejection fraction category., (© 2023 The Authors. European Journal of 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.)

In this observational and multicenter study, that included all patients who underwent a heart transplantation (HT) in Spain from 1984 to 2018, we analyzed the incidence, management, and prognosis of colorectal cancer (CRC) after HT. Of 6,244 patients with a HT and a median follow-up of 8.8 years since the procedure, 116 CRC cases (11.5% of noncutaneous solid cancers other than lymphoma registered) were diagnosed, mainly adenocarcinomas, after a mean of 9.3 years post-HT. The incidence of CRC increased with age at HT from 56.6 per 100,000 person-years among under 45 year olds to 436.4 per 100,000 person-years among over 64 year olds. The incidence rates for age-at-diagnosis groups were significantly greater than those estimated for the general Spanish population. Curative surgery, performed for 62 of 74 operable tumors, increased the probability of patient survival since a diagnosis of CRC, from 31.6% to 75.7% at 2 years, and from 15.8% to 48.6% at 5 years, compared to patients with inoperable tumors. Our results suggest that the incidence of CRC among HT patients is greater than in the general population, increasing with age at HT., 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., (Copyright © 2023 Sagastagoitia-Fornie, Morán-Fernández, Blázquez-Bermejo, Díaz-Molina, Gómez-Bueno, Almenar-Bonet, López-Granados, González-Vílchez, Mirabet-Pérez, García-Romero, Jose M., Rábago Juan-Aracil, Castel-Lavilla, Blasco-Peiro, Garrido-Bravo, De La Fuente-Galán, Muñiz and Crespo-Leiro.)

Competing Interests: Conflict of interest statement A.J.S.C.: none related to the present work. Outside the present work: consultancy fees from Astra Zeneca, Bayer, Boehringer Ingelheim, Edwards, Menarini, Novartis, Nutricia, Servier, Vifor, Abbott, Actimed, Arena, Cardiac Dimensions, Corvia, CVRx, Enopace, ESN Cleer, Faraday, Gore, Impulse Dynamics, Respicardia. A.P.M.: none related to the present work. Outside the present work: personal fees from Novartis, Bayer, AstraZeneca for participation in study committees. L.H.L.: none related to the present work. Outside the present work: grants: AstraZeneca, Vifor, Boston Scientific, Boehringer Ingelheim, Novartis, MSD; Consulting: Vifor, AstraZeneca, Bayer, Pharmacosmos, MSD, MedScape, Sanofi, Lexicon, Myokardia, Boehringer Ingelheim, Servier, Edwards Life Sciences, Alleviant; Speaker’s honoraria: Abbott, OrionPharma, MedScape, Radcliffe, AstraZeneca, Novartis, Boehringer Ingelheim, Bayer; Patent: AnaCardio. M.F.P.: none related to the present work. Outside the present work: Consultancy, speaker’s, institutional fees from AstraZeneca, Boehringer Ingelheim, CHF solution, Menarini, Novartis, Servier. M.G.C.-L.: none related to the present work. Outside the present work: Speakers honorary and/or consultancy fees from AstraZeneca, Boehringer Ingelheim, Novartis, Rovi, Vifor, Bayer, CareDx, Pfizer, Abbott and Medtronic. M.L.: none related to the present work. Outside the present work: speakers honoraria: AstraZeneca, Vifor, Boehringer Ingelheim, Novartis, Bayer, Sanofi; Consulting: Vifor, Boehringer Ingelheim. P.M.S.: honoraria for lectures from Servier, AstraZeneca, Respicardia, Menarini. Consultancy agreement and honoraria from Boehringer Ingelheim, Novartis, Vifor Pharma and Roche diagnostic. S.D.A.: grants and personal fees from Vifor and Abbott Vascular, and personal fees for consultancies, trial committee work and/or lectures from Actimed, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bioventrix, Brahms, Cardiac Dimensions, Cardior, Cordio, CVRx, Edwards, Farraday, Impulse Dynamics, Janssen, Novartis, Occlutech, Pfizer, Respicardia, Servier, Vectorious, and V-Wave. T.M.: none related to current work. Outside of current work, speaker honoraria; Boehringer Ingelheim, AstraZeneca, Edwards and Abbott. All other authors declare no conflict of interest for this contribution.

Despite the efforts made to improve the care of cardiogenic shock (CS) patients, including the development of mechanical circulatory support (MCS), the prognosis of these patients continues to be poor. In this context, CS code initiatives arise, based on providing adequate, rapid, and quality care to these patients. In this multidisciplinary document we try to justify the need to implement the SC code, defining its structure/organization, activation criteria, patient flow according to care level, and quality indicators. Our specific purposes are: a) to present the peculiarities of this condition and the lessons of infarction code and previous experiences in CS; b) to detail the structure of the teams, their logistics and the bases for the management of these patients, the choice of the type of MCS, and the moment of its implantation, and c) to address challenges to SC code implementation, including the uniqueness of the pediatric SC code. There is an urgent need to develop protocolized, multidisciplinary, and centralized care in hospitals with a large volume and experience that will minimize inequity in access to the MCS and improve the survival of these patients. Only institutional and structural support from the different administrations will allow optimizing care for CS., (Copyright © 2022 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: We aimed to describe recent trends in the use and outcomes of temporary mechanical circulatory support (MCS) as a bridge to heart transplantation (HTx) in Spain., Methods: Retrospective case-by-case analysis of 1,036 patients listed for emergency HTx while on temporary MCS in 16 Spanish institutions from January 1st, 2010 to December 31st, 2020. Patients were classified in 3 eras according to changes in donor allocation criteria (Era 1: January 2010/May 2014; Era 2: June 2014/May 2017; Era 3: June 2017/December 2020)., Results: Over time, the proportion of candidates listed with intra-aortic balloon pumps decreased (Era 1 = 55.9%, Era 2 = 32%, Era 3 = 0.9%; p < 0.001), while the proportion of candidates listed with surgical continuous-flow temporary VADs (Era 1 = 10.6%, Era 2 = 32%, Era 3 = 49.1%; p < 0.001) and percutaneous VADs (Era 1 = 0.3%, Era 2 = 6.3%; Era 3 = 17.2%; p < 0.001) increased. Rates of HTx increased from Era 1 (79.4%) to Era 2 (87.8%), and Era 3 (87%) (p = 0.004), while rates of death before HTx decreased (Era 1 = 17.7%; Era 2 = 11%, Era 3 = 12.4%; p = 0.037) Median time from listing to HTx increased in patients supported with intra-aortic balloon pumps (Era 1 = 8 days, Era 2 = 15 days; p < 0.001) but remained stable in other candidates (Era 1 = 6 days; Era 2 = 5 days; Era 3 = 6 days; p = 0.134). One-year post-transplant survival was 71.4% in Era 1, 79.3% in Era 2, and 76.5% in Era 3 (p = 0.112). Preoperative bridging with ECMO was associated with increased 1-year post-transplant mortality (adjusted HR=1.71; 95% CI 1.15-2.53; p = 0.008)., Conclusions: During the period 2010 to 2020, successive changes in the Spanish organ allocation protocol were followed by a significant increase of the rate of HTx and a significant reduction of waiting list mortality in candidates supported with temporary MCS. One-year post-transplant survival rates remained acceptable., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

This clinical consensus statement reviews the use of inotropic support in patients with advanced heart failure. The current guidelines only support use of inotropes in the setting of acute decompensated heart failure with evidence of organ malperfusion or shock. However, inotropic support may be reasonable in other patients with advanced heart failure without acute severe decompensation. The clinical evidence supporting use of inotropes in these situations is reviewed. Particularly, patients with persistent congestion, systemic hypoperfusion, or advanced heart failure with need for palliation, and specific situations relevant to implantation of left ventricular assist devices or heart transplantation are discussed. Traditional and novel drugs with inotropic effects are discussed and use of guideline-directed therapy during inotropic support is reviewed. Finally, home inotropic therapy is described, and palliative care and end-of-life aspects are reviewed in relation to management of ongoing inotropic support (including guidance for maintenance and weaning of chronic inotropic therapy support)., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Purpose: To describe the evolution of the serum levels of soluble HLA-G (s-HLA-G) during the first 12 months after heart transplantation (HT) and to correlate it with clinical outcomes., Methods: Observational study based in a single-center cohort of 59 patients who underwent HT between December-2003 and March-2010. Soluble HLA-G levels were measured from serum samples extracted before HT, and 1, 3, 6 and 12 months after HT. The cumulative burden of s-HLA-G expression during the first post-transplant year was assessed by means of the area under the curve (AUC) of s-HLA-G levels over time and correlated with the acute rejection burden -as assessed by a rejection score-, the presence of coronary allograft vasculopathy (CAV) grade ≥ 1 and infections during the first post-transplant year; as well as with long-term patient and graft survival. Mean follow-up was 12.4 years., Results: Soluble HLA-G levels decreased over the first post-transplant year (p = 0.020). The AUC of s-HLA-G levels during the first post-transplant year was higher among patients with infections vs. those without infections (p = 0.006). No association was found between the AUC of s-HLA-G levels and the burden of acute rejection or the development of CAV. Overall long-term survival, long-term survival free of late graft failure and cancer-free survival were not significantly different in patients with an AUC of s-HLA-G levels higher or lower than the median of the study population., Conclusions: Soluble HLA-G levels decreased over the first year after HT. Higher HLA-G expression was associated with a higher frequency of infections, but not with the burden of acute rejection or the development of CAV, neither with long-term patient or graft survival., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Statin therapy might have a beneficial prognostic effect in patients with COVID-19, given its immunomodulative, anti-inflammatory and anti-atherosclerotic properties. Our purpose was to test this hypothesis by using the COVID-19 registry of a Spanish university hospital., Methods: We conducted a single-center, observational and retrospective study in which hospitalized patients with COVID-19 diagnosed by PCR between March 2020 and October 2020 were included. By means of logistic regression, we designed a propensity score to estimate the likelihood that a patient would receive statin treatment prior to admission. We compared the survival of COVID-19 patients with and without statin treatment by means of Cox regression with inverse probability of treatment weighting (IPTW). The median follow-up was 406 days., Results: We studied 1122 hospitalized patients with COVID-19, whose median age was 71 years and of which 488 (43.5%) were women. 451 (40.2%) patients received statins before admission. In the IPTW survival analysis, prior statin treatment was associated with a significant reduction in mortality (HR: 0.76; 95% CI: 0.59-0.97). The greatest benefit of previous statin therapy was seen in subgroups of patients with coronary artery disease (HR: 0.32; 95% CI: 0.18-0.56) and extracardiac arterial disease (HR: 0.45; 95% CI: 0.28-0.73)., Conclusions: Our study showed a significant association between previous treatment with statins and lower mortality in hospitalized patients with COVID-19. The observed prognostic benefit was greater in patients with previous coronary or extracardiac atherosclerotic disease., (© 2022 Elsevier España, S.L.U. All rights reserved.)